Cerebrolysin Mechanism of Action

Pharmacology: Pharmacodynamics: The porcine brain-derived proteolytic peptide fraction stimulates cell differentiation, bolsters nerve cell function, and induces mechanisms of protection and repair. In animal experiments, Cerebrolysin directly influences neuronal and synaptic plasticity, thus improving learning. This has been shown in young, adult, and aged animals with reduced cognitive abilities. In models of cerebral ischaemia, Cerebrolysin reduced the infarct volume, inhibited oedema formation, stabilised microcirculation, doubled the survival rate, and normalised lesion-related neurological failure and learning deficits. Positive results were also obtained using models of Alzheimer's disease. In addition to its direct effects on neurons, Cerebrolysin appears to significantly increase the number of glucose transport molecules in the blood-brain barrier, thereby balancing out the critical energy deficit associated with this disease.
Quantitative EEG studies of healthy volunteers and patients suffering from vascular dementia have shown dose-dependent acute effects of elevated neuronal activity (increase in alpha and beta frequencies) after 4 weeks of treatment. Regardless of the cause of the disease, be it neurodegenerative dementia of Alzheimer's type or vascular dementia, Cerebrolysin therapy results in improvements in the objective cognitive abilities and in the activities of daily living. After only two weeks, there are improvements in the clinical global impression, which increase with continuation of the therapy. Also independent of the type of dementia, approximately 60-70% of patients respond positively to Cerebrolysin therapy. In the case of senile dementia of Alzheimer's type, the improved clinical state of the patient is maintained after the end of active treatment. In particular, the activities of daily living are improved and stabilised over the long term, which in general leads to a reduced need for patient care and supervision. On the basis of its neurotrophic (nerve growth factor-like) activity, Cerebrolysin can achieve a significant reduction, or in some cases even the cessation of progression, of neurodegenerative processes.
Pharmacokinetics: The porcine brain-derived proteolytic peptide fraction consists of short biological peptides similar or identical to those produced endogenously. Direct measurement of pharmacokinetic properties has not been performed successfully. Indirect pharmacokinetic data have been established on the basis of Cerebrolysin's pharmacodynamic profile. The neurotrophic activity of Cerebrolysin can be detected in blood plasma up to 24h after a single application.
Furthermore, components of the drug can cross the blood-brain barrier. Preclinical in vivo experiments revealed identical pharmacodynamic actions on the central nervous system following intra-cerebroventricular or peripheral application. Thus, indirect evidence for the passage of components of the drug across the blood-brain barrier has been established.
Toxicology: Preclinical safety data: Acute Toxicity/LD50: Rat male 68ml/kg BW IV; Rat female 74ml/kg BW IV; Dog male/female >52.2ml/kg BW IV.
Chronic Toxicity: Rat: Above 5ml/kg BW/day for 26 weeks: moderate changes in blood counts.
Dog: The highest applied dose of 9ml/kg BW/day for 28 days (corresponding to approximately 10 times the human therapeutic dose) and the highest applied dose of 4.5ml/kg BW/day (corresponding to approximately 5 times the human therapeutic dose) for 26 weeks showed no substance-related systemic intolerability.
Reproductive Toxicity: Intravenous administration of Cerebrolysin at doses toxic to the mother, or of the highest possible volume, showed no evidence of teratogenetic effects in any phase of reproduction in rats or rabbits, no influence on fertility, breeding capacity, posterity, and no embryotoxic or foetotoxic effects.
Mutagenicity: Cerebrolysin has shown no genotoxic or mutagenic potential, in vitro or in vivo.
Carcinogenicity: None of the studies of chronic toxicity or clinical experience have given any indication of carcinogenic effects.
Sensitising Potential: Larger molecular weight peptides with antigenic potential are excluded from the infusion solution during the manufacturing and quality control processes.
No influence on the immune system has been detected during testing. Tests revealed that Cerebrolysin does not result in the formation of antibodies or in cutaneous anaphylaxis. Cerebrolysin shows no histamine-stimulating potential and no haemagglutinating effects.