Cerebrolysin: composition, mechanism of action, MoA, best alternatives and FAQs
Neuroprotection is a term that is frequently come across in medical publications, mass media and pharmaceutical advertising. The possibilities of neuroprotection are incorporated in the brain itself, in genes and on the level of regulatory neuropeptides. The essence of neuroprotection is that the treatment both protects the affected group of neurons and ensures its further functioning. Is there an adequate pharmacological compound that can trigger natural mechanisms and maintain them when needed? In regard to this question, research, creation and testing of new pharmaceutical agents are and will be of the utmost importance in modern pharmacology. Cerebrolysin is one of the examples of a compound that was created based on the principles mentioned above.
Searching for new neuroprotectors is a complex process that requires combined effort of doctors, biologists and pharmacologists at all stages. Peptides like Cerebrolysin are of special attention here. In spite of their diversity, they are knit together by a number of common characteristics such as low dosage, absence of pronounced toxic effects, mild and long-term duration. Cumulatively, it can be asserted that a system of peptides in the body that has been formed during millions of years of evolution regulates all functions at many levels including processes ultimately leading to the neuroprotective effect. Peptides act naturally in the living organisms both at the systemic, and cellular levels.
- What is Cerebrolysin?
- History of Development
- Composition of Cerebrolysin
- Mechanism of Action of Cerebrolysin
- Safety Profile of Cerebrolysin
- What are the Main Indications for use of Cerebrolysin?
- How to Take Cerebrolysin?
- What are Alternatives to Cerebrolysin?
- Ever Pharma, Cerebrolysin Producer
- Is my Cerebrolysin Original?
- Can I store an Open Vial of Cerebro? Can I split the Contents of the Vial?
- Can Cerebrolysin cause prion infection?
- Where can I buy Cerebrolysin?
- Anecdotal References on Cerebrolysin
WHAT IS CEREBROLYSIN?
Cerebrolysin is a neuropeptide preparation with neuroprotective and neurorestorative effects. It’s a nootropic drug and one of the complex drugs with neurotrophic activity. In other words, Cerebrolysin is a neurometabolic stimulator based on low molecular weight biologically active neuropeptides (20%) and amino acids (80%) isolated from porcine brain tissue by enzymatic cleavage. Unlike the majority of peptide drugs, Cerebrolysin has all the amino acids which compose the central nervous system; this can explain many additional positive properties of the preparation.
It comes in an injection form 2ml, 5ml and 10ml ampules. Unfortunately, there is no such thing as Cerebrolysin tablets or nasal spray.
The mechanism of action is all about the ability to activate endogenous defense mechanisms (ESM), which include 4 main components: neurotrophics, neuroprotection, neuroplasticity, and neurogenesis.
Cerebrolysin injections has been thoroughly studied, including oligopeptide and membrane fractions, vitamin activity, amino acid, trace element composition and the effect on the homeostasis of brain trace elements and, most importantly, the peptide composition.
The drug is registered in more than 50 countries around the world. In Russia (USSR) it has been used since the early 1970s and has been included in the List of Vital & Essential Drugs since 1992.
HISTORY OF DEVELOPMENT
Cerebrolysin – perhaps the most efficient peptide nootropic – was developed back in 1949 by Gerhart Harrer, an Austrian Professor, and approved on 1 August 1954. He discovered that during the enzymatic hydrolysis of brain tissue, substances that have a stimulating effect on nerve cells and that regulate autonomic disorders are formed.
The first publications on the clinical use of Cerebrolysin date back to 1954-1955, when the arousing effect of the drug was discovered in patients with hypoglycemic coma . In a series of studies on 45 patients, half of them arose immediately after the drug administration. Evaluation of electroencephalogram (EEG) parameters showed the disappearance of pathological changes characteristic of hypoglycemia.
In subsequent years, the number of publications on the clinical use of Cerebrolysin injections in the treatment of mental disorders of various natures, cerebrovascular disorders, chronic brain injuries, and cerebral atherosclerosis increased. The accumulated experience of various uses of Cerebrolysin peptide was summarized at the Moscow Symposium in 1975, where data on the therapy of cerebral disorders in newborns were first reported.
In the 1950s the growth factor of nerves was discovered and the subsequent interest in the experimental study of neurotrophins gave rise to the idea of neurotrophic therapy and the explanation of the therapeutic mechanism of Cerebrolysin. Later studies showed that a pharmacological effect resembling the action of the nerve growth factor could persist for 24 hours after the administration of Cerebrolysin.
After many success stories, extensive research, and discovery of neurotrophic regulation, the popularity of the drug has increased drastically and now it can officially be used as a treatment for various cerebral disorders in more than 50 countries, mostly in Europe and Asia.
Cerebrolysin injections are used in the following cases:
- Strokes and stroke complications,
- Alzheimer’s disease and other types of dementia,
- Traumatic brain injuries (TBI),
- Spinal cord injuries,
- ADHD in children,
- Antidepressant-resistant depressions,
- Other cerebral diseases.
In Austria, the homeland of Cerebrolysin, it’s included in the Neurorehabilitation after stroke guidelines. In the US, Cerebrolysin has the status of a new drug approved by the FDA for private clinical use. Cerebrolysin is also approved in Canada.
COMPOSITION OF CEREBROLYSIN
The exact composition of Cerebrolysin is still unknown. Studies have shown that purified Cerebrolysin contains more than 100 oligopeptides and protein motifs with a molecular weight of up to 5800 Da.
The result of the Cerebrolysin composition research was the discovery of oligopeptides vital for the neurochemistry of the brain.
The drug contains the tripeptide Glu-Cis-Gly (glutathione) – a widespread antioxidant oligopeptide that is present in all tissue formations, adrenal glands, erythrocytes, cerebrospinal fluid, brain, lens of the eye. Its participation in redox reactions is of great importance .
The preparation contains the tripeptide thyroliberin with the amino acid sequence Glu-His-Pro, which is an antagonist of opioid activity. The main function of this oligopeptide is to enhance the secretion of thyrotropin by the anterior pituitary gland, as well as to stimulate the growth hormone corticotropin. 
An enkephalin motif with the amino acid sequence Tyr-Gly-Gly-Phе was also isolated from the lipid-free Cerebrolysin samples. Enkephalins are peptides with a wide range of action in the central nervous system and the peripheral nervous system. Their ability, together with other peptides, has been proven to regulate pain sensitivity, sexual behavior, motivation for satisfaction, and adaptation processes .
A stable collagen motif Gly-Pro-Hyp of brain supporting proteins was also found in Сerebrolysin. The motif can be used to reconstruct damaged and synthesize new supporting collagen and other proteins. 
The presence of active peptide fragments of neuropeptides NGF, enkephalins, orexin, galanin in the preparation was established as well.  With the exception of the ser-ser-phe-gly-ile fragment (corresponding to ABC-transport proteins), all identified peptides in the studied samples of Сerebrolysin are fragments of human proteome neuropeptides. The detection of biologically active NGF peptides in almost all fractions of the studied samples is of imperishable importance for the fundamental understanding of the neurotrophic activity of Cerebrolysin.
Cerebrolysin contains the PQRF peptide, which corresponds to a fragment of the recently discovered neuroactive neuropeptide VF. Unfortunately, there is still little data on the biological role of this neuropeptide, although it is known that it can activate mu-opioid and kappa-opioid receptors and regulate the hypothalamus .
The cys-cys-arg-gln-lys (CCRQK) peptide contained in the studied samples of Сerebrolysin is identified as a fragment of the orexin polypeptide (ORX gene). The CCRQK peptide, according to integral bioinformatics analysis, may be important for the interaction of orexin-A with receptors. Orexins affect a variety of human physiological functions, including energy metabolism, hormone balance, and fluid regulation in the body. Orexin-A also increases the expression level of NT-3 , which in turn supports the survival and differentiation of neurons, also stimulating the formation of new neurons and synaptogenesis.
Galanin acts primarily as a neuropeptide that modulates the secretion of the most important neurotrophic neurotransmitters acetylcholine, serotonin, and norepinephrine. The neurotrophic effects of galanin are being actively studied at the present time. Galanin is essential for the development and functioning of neurons; it stimulates the “sprouting” of axons .
Since Cerebrolysin is obtained by enzymatic fractionation of the brain extract of young pigs, which is characterized by a high antioxidant potential, it has been suggested that Cerebrolysin also has vitamin-like activity (in particular, vitamins B1, B12, E and folates), as well as superoxide dismutase activity.
Particular attention is drawn to the activity of vitamin B12 (cyanocobalamin). The presence of a stable high activity of cyanocobalamin in Сerebrolysin proves the preservation of the biocoordination bond of the cyano group with cobalt, which is fundamentally important for the full development of the neurotrophic effects of vitamin B12. Cyanocobalamin not only inhibits fatal damage to the cerebral cortex, but also, by participating in the synthesis of choline and methionine, has a beneficial effect on the liver, preventing the development of fatty hepatosis (in particular, with alcoholism). The indicated properties of cyanocobalamin can also explain the positive effect of long-term use of high doses of Cerebrolysin. .
Vitamin B1 (thiamine) is characterized by the most stable activity and high concentration in the preparation. In addition to the well-known enzymatic function, vitamin B1 controls the transport of Na+ ions across the neuron membrane, it participates in the exchange of acetylcholine, conduction of nerve impulses, and therefore has the status of a neurotransmitter .
The drug is strictly standardized in terms of the content of amino acids (alanine, arginine, aspartic acid, valine, histidine, glycine, glutamic acid, isoleucine, leucine, lysine, methionine, proline, serine, threonine, tryptophan, phenylalanine) in 1 ml of a ready-to-use solution. Amino acids play the role of a “building material” for the synthesis of all proteins. In addition, they are characterized by a number of physiological functions due to their chemical structure and biochemical properties. For example, on the basis of 20 “proteinogenic” (i.e., used to build proteins) amino acids, “non-protein” amino acids are synthesized. These “non-protein” amino acids (carnitine, taurine, gamma-aminobutyric acid – GABA – and dopamine) are also important for the functioning of the nervous system.
From a neurochemical point of view, amino acids can be subdivided as follows:
1) exciting (glutamate, aspartate);
2) inhibitory (GABA, beta-alanine, taurine, glycine);
3) neutral (lysine, arginine).
As a result, amino acids can regulate all the main nervous processes : arousal and inhibition, wakefulness and sleep, aggression and anxiety, synaptic plasticity, emotions, behavior, memory, learning. Taking into account that the bioavailability of amino acids when administered intravenously is close to 100%, it becomes clear that Cerebrolysin is an essential source of easily available amino acids necessary for brain recovery.
The preparation contains trace elements that play an important role in the functioning of a number of enzymes (sulfur, phosphorus, potassium, sodium, calcium, magnesium), and essential trace elements (lithium, selenium, zinc, tin, cobalt, silicon, iron, copper, manganese, chrome, vanadium).
Cerebrolysin is distinguished by superoxide dismutase activity, and this activity is ten times higher than that of a number of other neuroprotective drugs used in clinical practice (bilobil, actovegin, cerebrolysat) .
Despite significant progress in understanding the physiological effects of Cerebrolysin, there are a number of pressing issues related to clarifying the real composition of oligopeptides in the preparation, identifying, by testing the preparation, residual lipid and fatty acid fractions, its effect on the levels of metallothioneins, and finally, determining the most rational way of administering the preparation in order to obtain the maximum effect of its action.
Thus, further in-depth study of the composition and pharmacological properties of Cerebrolysin is an urgent research issue, the solution of which will allow a much deeper understanding of the mechanism of action of the drug, expand the scope and methods of its use.
MECHANISM OF ACTION OF CEREBROLYSIN
Cerebrolysin® is a neurotrophic peptidergic drug with multimodal pharmacological properties, indicated for the treatment of acute and chronic CNS disorders. The pathophysiological mechanisms targeted by Cerebrolysin belong to two distinct categories:
- Support of endogenous repair and recovery processes as a consequence of injury or degenerative disease;
- Protection against pathological events and cascades caused by an injury or a degenerative disease.
The natural repair and recovery processes in the CNS start immediately upon injury and play an important role in the continuous defense against neurodegeneration in chronic CNS disorders (e.g. Alzheimer’s disease). Cerebrolysin injections were shown to modify two major signalling pathways: the neurotrophic factor (NTF) and the sonic hedgehog (Shh) signalling pathway. These pathways regulate the cellular processes of neurogenesis, angiogenesis, dendritic arborisation, axonal sprouting, myelination, and remodelling of the neurovascular unit on a molecular level , thereby supporting the maintenance and repair of the neuronal network.
The pathological events and cascades after stroke or trauma lead to secondary injuries, which further compromise motor and cognitive functions of a patient. Among the most relevant molecular processes targeted by Cerebrolysin peptide in the acute phase of an injury are events of the ischemic cascade, like:
- Uncontrolled apoptosis,
- Overactivation of proteolytic enzymes,
- Overproduction of reactive oxygen species (ROS).
In the early post-acute phase, Cerebrolysin prevents the formation of toxic protein aggregates (amyloidosis) and lowers the level of inflammatory processes.
The low molecular weight composition of Cerebrolysin peptide allows it to relatively easily pass through the blood-brain barrier and go directly to the nerve cells. This is the difference between the action of Cerebrolysin and experimentally used drugs such as NGF (“nerve growth factor”), BDNF (“brain derived nerve factor”), etc., large molecules of which cannot overcome the blood-brain barrier and, as a result, have an extremely low therapeutic potential. At the same time, the high-tech and gentle process of Cerebrolysin production protects the neurotrophic properties of the extract from degradation.
SAFETY PROFILE OF CEREBROLYSIN
Cerebrolysin® injections are safe and well tolerated. The experience with Cerebrolysin during many years of clinical application, the information from post-marketing surveillance studies, and the safety data from double-blind, placebo-controlled clinical trials indicate a high degree of safety (e.g. significant reduction of mortality in CASTA study: the cumulative mortality by 90 days was 20.2% in the placebo and 10.5% in the Cerebrolysin group).
According to the EMA classification, Cerebrolysin peptide is in the “SAFE” category (PSUR reporting is required only every 13 years).
In general, reported adverse drug reactions from Cerebrolysin treated patients are transient and mild in intensity. The most frequently reported adverse reactions with Cerebrolysin are:
Despite the fact that Cerebrolysin injections have been used for more than 40 years mainly in adult therapeutic practice, its unique qualities encourage pediatricians to consider its use in children. In recent years it is being more and more prescribed for the treatment of neurological conditions of the younger patients.
The clinical efficacy of Cerebrolysin peptide in children was confirmed by Medvedev MI et al  in a study of premature infants with perinatal hypoxic-ischemic brain damage. After the treatment, the indicators of muscular-forward tonus and reflexes significantly improved, as well as the indicators of the formation of the bioelectric activity of the brain.
Please note that maintaining the sterile process of administration is very important. There is more information in the dosage recommendation section.
What are the main INDICATIONS FOR USE OF CEREBROLYSIN?
Vascular diseases of the brain are very wide-spread, the variety of their forms and characteristics (cerebrovascular crises, transient ischemic attacks (TIA), strokes, sometimes combined disorders of cerebral and coronary circulation), the difficulty and ineffective treatment of cerebral circulation disorders is increasing. Hence more and more attention has recently been paid to their prevention, early diagnosis, and post-stroke rehabilitation. Among other measures it is also important to start early drug therapy.
Traumatic brain injury (TBI)
TBI is one of the most common types of injuries and accounts for up to 50% of all types of injuries, with an upward trend in recent decades. In Russia alone, an average of 400-500 TBI cases per 100,000 people are registered annually, with people of working age (20-50 years old) mainly at risk. The overall mortality rate in severe TBI reaches 65–70%, and 50% of the injured who have had TBI, to one degree or another, lose their ability to work . Moreover, it’s a huge economic burden for the country’s social and tax systems. According to the CDC (America’s health protection agency) in the USA for example, the lifetime economic costs of TBI including direct and indirect medical costs were estimated to be approximately $ 76.5 billion (in 2010 dollars). 
In TBI, hypoxic and dysmetabolic disorders play a significant role in the pathogenesis of morphological disorders, along with the direct damage to nerve elements. TBI, especially severe, causes respiratory and circulatory disorders, which aggravates the existing dysregulatory cerebral disorders and, in aggregate, leads to more pronounced brain hypoxia.
The first publications on the clinical use of brain hydrolysates in hyperglycemic coma appeared back in 1954-1956. The use of Cerebrolysin injections in patients with acute TBI was based on an increase in the activity of superoxide dismutase and, as a consequence, a sharp decrease in the activation of peroxidation. The research results have shown the high efficiency of the administration of Cerebrolysin peptide in patients with acute TBI.
As a result of the complex interaction of the components that make up Cerebrolysin with neuronal structures, neurotrophic stimulation of various cell populations of the central and peripheral nervous system can be achieved.
According to A.E. Dubenko , immediately after the onset of TBI, LPO (lipid peroxidation) is activated, which has the same nature and quantitative characteristics as the effect of stress of various kinds. However, because there is a sharp violation of the processes of enzymatic oxidation and the release of metals of variable valence from the depot, which initiate and activate FRO (free-radical oxidation), the inhibition of LPO characteristic of stress does not occur after 24–48 hours. On the contrary a sharp activation of peroxidation is observed, which plays a significant role in the development of brain hypoxia and cerebral edema during trauma and occupies a leading place in the pathogenesis of post-traumatic symptoms.
142 patients were included in the CAPTAIN II study (out of 187 screened patients) . The CAPTAIN II study shows that after moderate to severe TBI, Cerebrolysin treatment improves the overall outcome at day 90 compared to placebo, confirming the results of a previous study conducted in a sample of Asian patients . It is extremely important that the clinical efficacy and safety of the use of high doses of Cerebrolysin injections has been proven in comparison with the previously accepted doses of 1, 2, 5, 10 ml in clinical practice. The introduction of Cerebrolysin in high doses (50 ml) made it possible to achieve better results in the treatment and rehabilitation of patients with moderate and severe TBI. 
As practice shows, repeated and long-term courses of treatment with Cerebrolysin peptide lead to an increase in the effectiveness of therapy, especially in relation to cognitive and behavioral functions.
Stroke (cerebrovascular disorders)
As it is officially stated on the website of the World Stroke Organisation (WSO), each year 17 million people suffer from stroke worldwide; of these nearly 6 million die and another 5 million are permanently disabled. Stroke is the second leading cause of death and the third leading cause of disability in lost disability-adjusted life years (DALYs).
There are two types of stroke:
- Ischemic stroke – a stroke that happens when the blood supply to a part of the brain is suddenly interrupted because of the arterial thrombosis;
- Haemorrhagic stroke – a stroke that happens when a blood vessel in the brain bursts, spilling blood into the spaces surrounding brain cells.
Cerebrolysin® injections are recommended in the stroke treatment guidelines of top reference countries (Austria, Canada and Germany). For example in the Austrian guidelines it is suggested that Cerebrolysin may have a positive effect on the restoration of the upper extremities after stroke if taken at the dose of 30 ml for 3 weeks and longer. Cerebrolysin in Canada is said to be beneficial for aspects of upper limb function following stroke and is described and recommended in the Evidence-Based Review of Stroke Rehabilitation (EBRSR) by Robert Teasell, MD et al  under the Canadian Partnership for Stroke Recovery (CPSR).
Its efficacy has been proven in 36 double-blind-studies and trials with more than 5.000 patients.
In 2017 a group of scientists combined the results of two identical stroke studies (CARS-1 and CARS-2) concerning the efficacy of Cerebrolysin on motor recovery during early rehabilitation.  Both studies had a prospective, randomized, double-blind, placebo-controlled design. Treatment with 30 ml Cerebrolysin once daily for 3 weeks was started 24-72 h after the stroke onset. In addition, patients participated in a standardized rehabilitation program for 21 days that was initiated within 72 h after the stroke onset. The results of the study showed that Cerebrolysin had a beneficial effect on motor function and neurological status in early rehabilitation patients after acute ischemic stroke. Safety aspects were comparable to placebo, showing a favourable benefit/risk ratio.
With craniocerebral trauma, as with a stroke, the severity of the case and the timely assistance of doctors are extremely important. If the injury is serious, the patient can be assisted in the intensive care unit, and the main task here is to reduce the area of the lesion, because it will be much more difficult to restore the brain tissue and function than to protect it.
Cerebrolysin peptide stimulates natural recovery processes after stroke. These processes are most prominent during the first 3 months post-stroke. Therefore, Cerebrolysin can be given within this broad treatment window. Both the research and clinical data for Cerebrolysin indicate that the best treatment effects are seen when Cerebrolysin is administered as soon as possible after the stroke and continued during the natural recovery phase.
Life expectancy in industrialized countries has been increasing by two years per decade in the last 20 years and is predicted to further surge. An increase in the life expectancy of the population inevitably leads to an increase in the load because of the diseases associated with the aging of the central nervous system (CNS), brain and blood vessels. In addition to the “epidemic” of stroke, medicine is faced with another problem – dementia. Dementia affects at least 30 million people in the world. According to forecasts, by 2050 the number of patients with dementia will reach 120 million. The high prevalence of ischemic stroke and cognitive impairment necessitates a rational choice of drugs for the rehabilitation and prevention of these diseases.
In the treatment of dementia, early diagnosis is of utmost importance. Unfortunately physicians have a tendency to regard memory complaints of their patients as a normal aging process instead of raising early awareness of mild cognitive impairment.
As it is stated on the official web-site of Cerebrolysin, mild cognitive impairment (MCI) is the earliest stage of dementia. People with MCI may have some difficulties with memory and trouble recalling some words, but they manage their everyday routine well. However, 70% of those diagnosed with MCI progress to dementia or Alzheimer’s disease (AD) at some point.
People with moderate or advanced dementia typically need round-the-clock care and supervision to prevent them from harming themselves or others. They also may need assistance with daily activities such as eating, bathing, and dressing.
Cerebrolysin peptide shows that it can slow the progression of the disease and be already part of the therapy in the beginning of MCI. In Russia it was included in the Anti-dementia plan for 2025 under the Ministry of HealthCare of the Russian Federation.
The Cochrane Library published a critical study of Cerebrolysin for Vascular Dementia in 2013 and then in 2019 . Six randomised controlled trials with a total of 597 participants from China, Russia and Romania with mild to moderate dementia were included in the study. It was stated that it might have positive effects on the improvement of cognitive function and global function in older patients with VaD of mild to moderate severity. But scientists were quite skeptical and stressed that further trials need to be conducted in order to provide recommendations for treatment.
Another complex study investigated Cerebrolysin in mild to moderate Alzheimer’s disease. All randomized double-blind placebo-controlled studies on 30 ml/day of Cerebrolysin in mild-to-moderate AD were included. This meta-analysis provided evidence that Cerebrolysin has an overall beneficial effect and a favorable benefit-risk ratio in patients with mild-to-moderate AD. The therapeutic agent was recommended for mild-to-moderate AD. 
Taking into account all the indications for use, it is still important to be aware of the fact that recovery and treatment of such serious conditions as mentioned above requires a multimodal approach including physical activity, physiotherapy and medical therapy combined together. Cerebrolysin can help but one should not regard it as a magic shot which would do wonders.
HOW TO TAKE CEREBROLYSIN?
Cerebrolysin® injections belong to drugs with neuroprotective and neuro-regenerative functions used in the acute phase and rehabilitation. It is recommended to start Cerebrolysin therapy as early as possible, usually within a few hours after stroke / TBI. Cerebrolysin should be used as an adjunct to standard treatment.
|Condition||Daily dosage||Initiation of treatment||Duration of treatment|
|Stroke||20 – 50 ml||asap||10 – 21 days|
|Vascular dementia||10 – 30 ml||asap||1 cycle: 5 days a week/ 4 weeks2-4 cycles per yearIn the next courses of therapy, the frequency of use can be reduced from daily applications to 2-3 applications per week.|
|Alzheimer’s disease||10 – 30 ml||asap||1 cycle: 5 days a week/ 4 weeks2-4 cycles per yearIn the next courses of therapy, the frequency of use can be reduced from daily applications to 2-3 applications per week.|
|Traumatic brain injury (TBI)||20 – 50 ml||asap||7 – 30 days|
Route of Administration
|10ml – 50ml||diluted to at least 100ml total volume with Saline, Ringer solution or 5% glucose solution||Infuse slowly within 15 minutes|
|up to 10ml||undiluted||inject slowly for 3 minutes|
|up to 5 ml||undiluted||inject slowly for 3 minutes|
The IV and IM injection has to be administered immediately after opening the ampoule! Do not store the infusion solution, start the infusion as quickly as possible after the dilution!
Cerebrolysin peptide should not be mixed with balanced amino acid solutions, vitamins and cardiovascular medicinal products.
Special precautions to guarantee sterility must be taken during the dilution and administration of Cerebrolysin:
- Remove the solution from an ampoule immediately prior to use;
- Do not leave an open ampoule on the treatment table;
- Always use disposable one-way IV infusion sets and cannulas;
- When Cerebrolysin is administered via a long-term IV catheter, the catheter has to be rinsed before and after the application with physiological sodium chloride solution;
- Pay special attention to recommended infusion/injection times.
What are ALTERNATIVES TO CEREBROLYSIN?
We are all unique. And we can react differently to the slightest variations in the composition of preparations, and a set of auxiliary substances. At the CosmicNootropic store, Cerebrolysin is one of the most popular peptide nootropics. But for some people, depending on the indications, Cortexin might be a better option.
It is a mixture of neuropeptide fractions, amino acids, vitamins, and minerals, all of which have a pronounced but subtle positive effect on the brain. The compound is produced by the Russian pharmaceutical company GeroPharm. Similar to Cerebrolysin, Cortexin is based on neuropeptides and amino acids. However, there is a difference: Cortexin has a significantly larger amount of peptide fractions and fewer amino acids. While the former is produced from pig brains only, the latter is extracted mostly from young horned cattle cerebral cortex by acetic acid extraction.
Cortexin has the following effects:
- Nootropic effect: Improves higher cerebral functions, processes of learning and memory, concentration, attention and tolerance to mental and physical stress;
- Neuroprotective effect: protects neurons against different endogenous neurotoxic factors (glutamate, calcium ions and free radicals) and reduces toxic impact of psychotropic agents;
- Antioxidant effect: inhibits lipid peroxidation, increases survival of neurons under oxidative stress and hypoxia;
- Tissue-specific effect: activates metabolism of neurons of central and peripheral nervous system as well as reparative processes; also, promotes stimulation of cortical function and general improvement of the nervous system.
Due to its high safety profile Cortexin is suitable for all ages and is often prescribed for children at lower doses (5mg). However in case of Cortexin mild allergic reactions are more possible compared to Cerebrolysin peptide.
Can Cortexin and Cerebrolysin be used at the same time?
Cerebrolysin is a nootropic and, like Cortexin, contains animal brain peptides. However, with a deeper analysis, it becomes apparent that the ratio and composition of the peptides that make up Cerebrolysin and Cortexin are different.
Experts do not consider it effective to combine these drugs, but quite often recommend to use them in succession or alternate the courses.
Cellex® is a neuroprotector for the treatment of acute disorders of cerebral circulation, consisting of a balanced and stable mixture of biologically active proteins and polypeptides with a multifunctional effect. Both preparations come in injection form. But unlike Cerebrolysin which is extracted from the brain of young pigs, Cellex is produced from pig embryonic brain tissue that’s why the concentration of neuropeptides is higher. And Cellex is more expensive in comaprison to Cerebrolysin.
Cellex is taken in the following cases:
● Cerebrovascular diseases,
● Acute disorders of cerebral circulation in the acute and early rehabilitation period of the course of the disease as part of complex therapy.
Cellex activates secondary neuroprotection by: stimulation of synaptogenesis processes, restoration of autophagy signals, and improvement of tissue immunoregulation with inhibition of immunogenic cytotoxicity of macrophages. This process is accompanied by tissue-specific and systemic reparative action of the product with the restoration of regenerative and reparative potential of brain cells, a decrease of the number of damaged cells and intensity of perifocal edema in the area of penumbra (making possible to achieve a significant limitation of the site of the brain tissue necrosis) with the restoration of microcirculation and total perfusion.
Memoprove® (N-pep 12)
N-PEP-12 is a pig brain-derived peptide blend obtained by enzymatic hydrolysis of purified proteins of nerve cells in compliance with all the GMP standards, using technologies approved by representatives of the European healthcare system. The composition of Memoprove is very similar to Cerebrolysin (some even call it “Cerebrolysin pills”). Its efficacy is confirmed by preclinical studies, as well as by the results of placebo-controlled studies in groups of volunteers [11, 12].
The mechanisms of action of Memoprove (N-pep 12) are implemented in two main directions:
- Stimulation of neuroplasticity – the formation of new interneuronal connections and regenerative processes leading to an improvement in cognitive functions such as memory, attention and concentration;
- Stimulation of neuroprotection – protection of neurons and connections between them to prevent damage to nerve cells against the background of exposure to adverse factors (stress, toxic substances from the environment, ischemia, etc.).
It has been reliably proven that Memoprove:
- Slows down main processes causing memory problems;
- Supports optimal brain function;
- Stimulates the production of new brain cells (neurogenesis);
- Increases transport and utilization of glucose by the brain;
- Increases the lifespan and energy production of senescent brain cells.
Memoprove has a favorable safety profile. There were no statistically significant differences in the incidence of adverse events between the groups receiving N-PEP-12 and placebo.
Please note that Memoprove is a food supplement that is not designed to treat any disease. And it is less effective compared to Cerebrolysin peptide.
Cerluten® is a cytomaxe which means that it is a natural peptide, derived from the animal brain cortex and designed to protect, restore and improve functions of the central nervous system and the brain.
There are also Ukranian and Belorussian generics similar to Cerebrolysin produced under the brand name Ceregin® and Cerebrolysat®. And they are also derived from the brains of cattle and porcine.
However Cerebrolysin is considered to be of higher quality and safety compared to its generics. And if we are talking about the products extracted from raw tissues, the technologies and purification process play a crucial role in the production of a medication.
Cerebrolysin injections vs P21 nasal spray
What is the difference between Cerebrolysin and P21 peptide? Should one choose a nasal spray over an injection? – Well, actually it is not quite right to compare these two products. Let’s see why.
P21 is a peptide that is artificially synthesized and is not used as a medicine in any country. One might also want to take caution with intranasal RoA as there is some negative feedback on that.
Cerebrolysin on the other hand is a complex of essential substances and it also has P21 in its composition. Besides, it also contains neuropeptides, amino acids, and minerals. It’s a very reliable and safe drug that has been successfully used in many countries for several decades. Its side effects are extremely rare. And they are mostly attributed to its form of administration as the drug is only used IV or IM. And not without reason. – On the forums, you can find some cases when people tried to use Cerebrolysin unconventionally and this had negative consequences: unlike injections, this is just not safe.
That’s why we strive to promote the on-label use of the products and follow the official instructions if you want to minimize risks.
EVER Pharma, Cerebrolysin Producer
We keep looking at producers of the popular products in our store: one of them is EVER Pharma – the producer of Cerebrolysin.
About the company
The company was founded under the brand name EBEWE Pharma in 1934 Vienna, Austria. Later, the company became independent EVER Pharma GmbH. Today the main factory is located in Jena, Germany. It has many years of experience in such a complex industry as the development and production of sterile dosage forms and is considered a recognized partner in the pharmaceutical manufacturing industry. The company has 25 offices and representative offices in more than 70 countries. In addition to European countries, EVER Pharma also supplies products to the worldwide market, for example, to Brazil and Japan. It is one of the world-class leaders in such therapeutic areas as diseases of the nervous system and emergency conditions.
EVER Pharma offers high-quality products in the field of neurology and emergency conditions. The product range includes drugs for the treatment of stroke, head injuries, vascular dementia, Alzheimer’s disease, Parkinson’s disease, hypertension, and epilepsy. The company also provides clinically approved nutritional supplements to support memory function and enhance mental performance. Moreover, in addition to its own high-quality sterile products in ampoules, test tubes, and ready-made syringes, the company also manufactures the latest implants for other companies. It also offers the full range of services related to the production and testing of sterile dosage forms, as well as support in the development of drugs and the creation of files. In total, the production capacity of EVER Pharma is up to 130 million units per year.
The drugs fully comply with the requirements of international pharmaceutical quality standards. The company has a license of Good Manufacturing Practice (ЕU GMP ISO 13485:2013, ISO 9001:2008).
Why do pharmacies sell Cerebrolysin in different packages, with either Ebewe Neuro Pharma or EVER Neuro Pharma listed as a manufacturer on the package? Are they different?
At the end of 2008, the company “Ebewe Pharma Ges. m.b.H Nfg. KG” was reorganized. The company’s department that had specialized in neurological drugs, became a subsidiary with a brand name “EBEWE Neuro Pharma GmbH”. In 2010, the company “EBEWE Neuro Pharma GmbH” was renamed to “EVER Neuro Pharma GmbH”. And because the shelf life of Cerebrolysin is 5 years, you might have seen both the old and the new packages on the shelf. Therefore, Cerebrolysin in both packages is the same drug from the same manufacturer, produced in the same facility.
Is my Cerebrolysin original?
Cerebrolysin is a high-quality product that is designed to treat neurological conditions and produced by EVER Neuro pharma. Sometimes counterfeiters copy the external layout of the box but it may contain dangerous compounds inside. So it’s important to make sure you obtain your product from a trustworthy vendor.
Please note that Cerebrolysin is now released without a hologram on the pack. Packs with holograms are from older batches.
Why does the hologram on the box of Cerebrolysin contain hieroglyphs?
Some may wonder why the holograms on the Cerebrolysin box look like Chinese characters.
Carton packages from older batches used to be sealed with a silver homogeneous hologram. When it was peeled off, its silver fragments remained on the box. And they indeed looked like Chinese characters, but only visually.
Some Unconventional forms of Cerebrolysin?
Just like many other drugs which are popular among nootropic enthusiasts around the world, the conventional form of Cerebrolysin peptide is being modified and adopted to better fit the purposes of the customers.
Here is an anecdotal report and discussion devoted to the oral version of Cerebrolysin. It is supported by a paper  that has studied the effects of a single oral dose of the Cerebrolysin solution (30 ml) on brain bioelectrical activity and on cognitive performance in healthy elderly people. The results of the study suggested that the oral Cerebrolysin might be useful for the treatment of memory impairment and brain damage in eldely subjects with or without neurodegenerative disorders.
There were also some anecdotal reports of those who tried the intranasal route of administration in pursuit of avoiding unpleasant injections. It should be noted that they reported serious and long term and/or permanent side effects to Cerebrolysin Nasal Spray.
Is it Safe to combine Cerebrolysin with other nootropics?
Given the pharmacological profile of Cerebrolysin injections, special attention should be given to possible additive effects when co-prescribing with antidepressants, including MAOIs (monoamine oxidase inhibitors). In such cases it is recommended to reduce the dosage of the antidepressant.
Do not mix Cerebrolysin peptide and balanced amino acid solutions in a single solution for infusions. Cerebrolysin is also incompatible with solutions containing lipids or modifying the pH of the medium (5-8).
The compatibility of the preparation with the following standard infusion solutions was checked and confirmed (for 24 hours at room temperature and with illumination):
- 0.9% solution of sodium chloride (9 mg NaCl / ml);
- Ringer’s solution (Na+ – 153.98 mmol/l, Ca2+ – 2.74 mmol/l, K+ – 4.02 mmol/l, Cl- –163.48 mmol/l);
- 5% glucose solution.
It is permissible to use Cerebrolysin simultaneously with vitamins and preparations for cardiac circulation improvement, but these preparations should NOT be mixed in the same syringe with Cerebrolysin.
Can Cerebrolysin help cope with post-Covid Anosmia?
We have come across a recent article by Sherifa Ahmed Hamed MD of Assiut University (Egypt)  where the researchers hypothesize that Cerebrolysin, a drug of neurotrophic and neuroprotective properties, can be used to treat patients with persistent post-COVID anosmia or ageusia or promote functional recovery of smell and taste deficits.
Cerebrolysin was prescribed in a dose of 10 ml ampoule once daily through intramuscular injection for five times per week, for a total of 20 treatments (for 4 weeks), after which the cycle was repeated again for at least 8 more weeks.
The study ended in March 2021 and the results are still to be published which does not allow us to assume yet that it indeed may have a beneficial effect in regards to Covid-2019.
Can I store an open vial of Cerebro? Can I split the contents of the vial?
There are many anecdotal reports including quite trustworthy ones (Leo from TheLongLived for example) where people split the contents of a vial and store them for multiple usage. Please note that it might lose some of its potency as it gets rapidly oxidized.
Still if you feel like it, it is considered economically feasible to buy 10ml ampoules and then split them into capped syringes and store in the fridge (do not freeze) for 24h. Prior to an injection it should be taken out of the fridge, warmed and for sterility purposes the needle better be changed too. The compound is ready for use. You can read more about it on Reddit.
However one should be aware of the fact that according to the official instructions it is recommended to use the solution of a vial only ONCE, when you open it. Do not store an open ampoule.
Can taking Cerebrolysin cause Prion Disease?
Some people are concerned whether it is possible to get infected with prions by taking medications of animal origin (Cortexin, Solcoseryl, Cerebrolysin etc). First of all we would like to provide a short description of what prion diseases are.
Prion diseases (PD), or transmissible spongiform encephalopathies (TSE), are a group of neurodegenerative disorders characterized by rapidly progressive dementia and movement disorders. The term “prion” appeared in the middle of the 20th century. The nature of spongiform encephalopathy remained unclear for a long time. In the 60s, British researchers T. Alper and J. Griffith hypothesized that some TSEs are caused by pathogens composed exclusively of proteins. They found that the pathogen causing scrapie in sheep and Creutzfeldt-Jakob disease has unusual properties and exceptional resistance to ionizing radiation. In 1982 S. Prusiner isolated this agent from the brains of sick animals, and then studied its properties. The infectious agent consisted of one protein. Based on the experimental data obtained, the concept of prion proteins was formulated and then became generally accepted.
All mammalian prion diseases known to date are caused by the PrP protein. Its form with a normal tertiary structure is designated as PrPC (“C” for common or cellular). The pathological form of the infectious protein is called PrPSc (“Sc” for scrapie – sheep pruritus, after the name of one of the first diseases with an established prion nature) or PrPTSE (“TSE” for Transmissible Spongiform Encephalopathies).
There are three variants of the occurrence of prion diseases:
- direct infection,
- hereditary and
- sporadic (arising spontaneously) forms.
Infection of both humans and animals (mainly horned cattle) is most often alimentary (through the gastrointestinal tract), i.e. the main way of acquiring the disease is through the consumption of contaminated food.
Prion infection can also occur in case of use of non-sterile surgical instruments. If contaminated material gets on the skin, it is first disinfected with 4% sodium hydroxide solution for 5-10 min, and then washed with running water . In fact Cerebrolysin has sodium hydroxide in its composition as an excipient.
There are no treatments for PD today. Prescriptions are limited to supportive care. Genetic counseling is recommended for relatives of patients with a family history of PD. The development of special vaccines for animals is underway, which in the future should help in the creation of a vaccine against PD for humans.
There are medications that are produced with the use of animal tissue in modern medicine. Is there a potential risk of PD for patients using them?
First of all it’s important to note that Cerebrolysin is derived from pig brain only (industrially since 1943), in which no prion diseases have been identified. Besides this fact the biological safety of products based on animal tissues from prion contamination is ensured by specially developed procedures that meet the requirements of the European Medicines Agency (Note for Guidance 410/01), as well as the requirements of the European Pharmacopoeia (Eur. Ph. 7.0, 01/2008: 50107, clause 5.1.7 “Virus safety” and Eur. Ph. 7.0, 01/2008: 50208, clause 5.2.8. “Minimising the risk of transmitting animal spongiform encephalopathy agents via human and veterinary medicinal products”). Raw material taken from young healthy animals undergoes the most stringent selection and is used only after confirming viral safety and obtaining a veterinary certificate. The production of Cerebrolysin is based on modern technological processes aimed at isolating low-molecular water-soluble peptides from the tissues of raw materials. The process makes it possible to completely exclude peptides with a molecular weight of more than 10 kDa from the final preparation, while, as known, the molecular weight of prions is 33–35 kDa.  It is important to note that the substance of the drug (cerebrolysin dry extract) is an intermediate product and is not directly used for the preparation of a sterile drug, but is processed at additional technological stages. Thus, based on the properties of prions and taking into account the conditions for obtaining the peptide substrate the possibility of the presence of prion proteins in the solution is said to be non-existent.
WHERE CAN I BUY CEREBROLYSIN?
There are several companies where you can buy original Cerebrolysin, namely:
- Cosmicnootropic.com is a reliable supplier which has been around for over 5 years. They mainly specialize in supplying original Russian medications that otherwise would be difficult to obtain.
- Rupharma.com is another trustworthy supplier with many positive reviews. They focus on delivering medical products from Russia, Europe and India.
Let’s compare current prices and the delivery cost for Cerebrolysin. Prices listed in the table below are regular as of August 2021 for one unit without any special offers or discounts.
ANECDOTAL REFERENCES ON CEREBROLYSIN
There are many anecdotal reports on the use of Cerebrolysin injections on Reddit.
This is probably one of the most comprehensive reviews of Cerebrolysin where a person explains the positive sensations, the mode of administration and compares it to other nootropics like Phenlypiracetam, Phenibut or Noopept. In another detailed report a person describes the positive manifestations and few drawbacks on a daily basis.
There are of course various reports on different stacks with Cerebrolysin. Here a person stacked Cerebrolysin injections and Buthylphthalide with some positive feedback and dosage recommendations. And this anecdotal report was on the r/TheLongLived subreddit from a person who used to take phenibut, benzo and was still taking Kratom at the same time with Cerebrolysin. And it seemed to have a mild yet noticeable effect on the person.
Of course there are also lots of reviews on the Russian pharmaceutical websites like RLSNET.RU (a registry of medicines of Russia, which is, in fact, an Encyclopedia of Medicines and Pharmacy Products) and EAPTEKA.RU (an online pharmacy for the purchase and delivery of goods for health, beauty and well-being) which might be interesting to read as well.
Also check out this video with one of the well-known nootropic enthusiasts talking about his experience:
Please feel free to indulge in a discussion devoted to Cerebrolysin and share your experience via Reddit. We would very much appreciate your comments.
- H Hetzel, E Niedermeyer (1955). Arousing effects of brain hydrolysate in hypoglycemic coma and their electroencephalographic appearance. https://pubmed.ncbi.nlm.nih.gov/13249577/
- Dubenko AE (1991). The role of lipid peroxidation and the activity of energy metabolism enzymes in the pathogenesis of acute closed craniocerebral trauma. https://pubmed.ncbi.nlm.nih.gov/1792780/
- Akai F., Hiruma S. (1992). Neurotrophic factor-like effect of FPF 1070 on septal cholinergic neurons after transections of fimbria-fornix in the rat brain. https://pubmed.ncbi.nlm.nih.gov/1515704/
- De Wied D. (1997). Neuropeptides in learning and memory processes. https://pubmed.ncbi.nlm.nih.gov/9062665/
- Gromova OA et al (1998). Effects of cerebrolysin on the oxidant homeostasis, the content of microelements and electrolytes in children with minimal brain dysfunction. https://pubmed.ncbi.nlm.nih.gov/9505400/
- Leppala JM et al (1999). Different risk factors for different stroke subtypes. https://pubmed.ncbi.nlm.nih.gov/10582974/
- Alvarez XA et al (2000). Oral Cerebrolysin enhances brain alpha activity and improves cognitive performance in elderly control subjects. https://pubmed.ncbi.nlm.nih.gov/10961443/
- Goldstein LB et al (2001). Primary prevention of ischemic stroke: a statement for healthcare professionals from the Stroke Council of the American Heart Association. https://pubmed.ncbi.nlm.nih.gov/11136703/
- Plum F (2001). Neuroprotection in acute ischemic stroke. https://pubmed.ncbi.nlm.nih.gov/11277833/
- Gomazkov OA (2005). Neurotrophic and growth factors of the brain: regulatory specificity and therapeutic potential. https://pubmed.ncbi.nlm.nih.gov/15909662/
- Volc D, Alvarez XA, Moessler H (2005). Cognitive Effects of the Novel Neuroprotective Dietary Supplement N-PEP-12: Evidence from a Self-Assessment Study. https://www.xediton.com/wp-content/uploads/2017/05/Volc-et-al.pdf
- Windisch M et al (2005). N-PEP-12™ – a novel peptide compound that protects cortical neurons in culture against different age and disease associated lesions. https://pubmed.ncbi.nlm.nih.gov/15750682/
- Gromova OA et al (2006). An oligopeptide membrane fraction of cerebrolysin. https://pubmed.ncbi.nlm.nih.gov/16921723/
- Suarez V et al (2006). The axotomy-induced neuropeptides galanin and pituitary adenylate cyclase-activating peptide promote axonal sprouting of primary afferent and cranial motor neurones. https://pubmed.ncbi.nlm.nih.gov/17004919/
- Cline MA et al (2008). Short-term anorexigenic effects of central neuropeptide VF are associated with hypothalamic changes in chicks. https://pubmed.ncbi.nlm.nih.gov/18540998/
- Yamada N et al (2009). Orexins increase mRNA expressions of neurotrophin-3 in rat primary cortical neuron cultures. https://pubmed.ncbi.nlm.nih.gov/19026718/
- Bin Li et al (2010). Neurotrophic peptides incorporating adamantane improve learning and memory, promote neurogenesis and synaptic plasticity in mice. https://www.sciencedirect.com/science/article/pii/S001457931000520X
- Torshin IYu, Gromova OA (2012). Expert data analysis in molecular pharmacology. https://artlib.osu.ru/web/books/content_all/4911.pdf
- Medvedev MI et al (2014). Clinical and neurophysiological objectification and evaluation of treatment efficacy in children with perinatal hypoxic-ischemic injury of the CNS. https://pubmed.ncbi.nlm.nih.gov/24874320/
- Gromova OA et al (2015). Neurotrophic and antioxidant potential of neuropeptides and trace elements. https://www.researchgate.net/publication/307647263_Neurotrophic_and_antioxidant_potential_of_neuropeptides_and_trace_elements
- Poon W et al (2015) Cerebrolysin Asian Pacific trial in acute brain injury and neurorecovery: design and methods. https://pubmed.ncbi.nlm.nih.gov/25222349/
- Serge Gauthier et al (2015). Cerebrolysin in mild-to-moderate Alzheimer’s disease: a meta-analysis of randomized controlled clinical trials. https://pubmed.ncbi.nlm.nih.gov/25832905/
- Won Hyuk Chang et al (2016). Cerebrolysin combined with rehabilitation promotes motor recovery in patients with severe motor impairment after stroke. https://bmcneurol.biomedcentral.com/articles/10.1186/s12883-016-0553-z
- Guekht A et al (2017). Safety and efficacy of Cerebrolysin in motor function recovery after stroke: a meta-analysis of the CARS trials. https://pubmed.ncbi.nlm.nih.gov/28707130/
- Robert Teasell et al (2018). Evidence-Based Review of Stroke Rehabilitation. https://www.ebrsr.com/sites/default/files/Ch.%2010%20Upper%20Extremity%20Motor%20Interventions_v20.pdf
- Zavadenko NN et al (2018). Human prion diseases: current issues. https://www.mediasphera.ru/issues/zhurnal-nevrologii-i-psikhiatrii-im-s-s-korsakova/2018/6/downloads/ru/1199772982018061088
- Shuhui Cui et al (2019). Cerebrolysin for vascular dementia. https://pubmed.ncbi.nlm.nih.gov/31710397/
- Torshin I Yu et al (2019). Cerebrolysin peptides as mood stabilizers. https://pubmed.ncbi.nlm.nih.gov/31994517/
- Ivanova NE et al (2020). Review of results from the CAPTAIN II trial: efficacy and safety of Сerebrolysin in neurorecovery after moderate-severe traumatic brain injury. https://neurologic.ru/biblioteka-znanij/obzor-po-rezultatam-issledovanija-captain-ii/
- Muresanu DF et al (2020). Efficacy and safety of cerebrolysin in neurorecovery after moderate-severe traumatic brain injury: results from the CAPTAIN II trial. https://pubmed.ncbi.nlm.nih.gov/31897941/
- Gavrilova SI, Alvarez A (2020). Cerebrolysin in the therapy of mild cognitive impairment and dementia due to Alzheimer’s disease: 30 years of clinical use. https://pubmed.ncbi.nlm.nih.gov/32808294/
- Sherifa AH (2021). Cerebrolycin for Treatment of Covid-related Anosmia and Ageusia. https://clinicaltrials.gov/ct2/show/NCT04830943