CEBROTONIN TABLETS

Indications

• Cognitive impairment
• Dementia
• Myoclonus
• Vertigo
• Dystonia
• Adjunct therapy in cognitive dysfunction
• Recovery from brain injuries

Dosage

Children: Refer to the BNF for Children for specific dosing information.

Adults: By mouth, 100–200 mg four times a day.

Mechanism of action

Piracetam interacts with the polar heads in the phospholipid membranes, reorganizing lipids and influencing membrane function and fluidity. This interaction enhances membrane stability, allowing normal function of transmembrane proteins and improving neurotransmission. It promotes neuroplasticity and has demonstrated anticonvulsant effects. Additionally, piracetam improves platelet membrane fluidity and reduces erythrocyte adhesion, which may alleviate vasospasm.

Pharmacodynamics

Piracetam modulates various neurotransmitter systems including cholinergic, serotonergic, noradrenergic, and glutamatergic pathways. It increases the density of postsynaptic receptors, enhancing cognitive processes such as learning and memory without causing sedation. It also has neuroprotective effects against neuronal damage from hypoxia and intoxication, and has been shown to reduce neuronal loss in withdrawal-related scenarios.

Pharmacokinetics

Piracetam is well-absorbed after oral administration and has a bioavailability of approximately 100%. It is widely distributed in body tissues, with the highest concentrations found in the brain. The drug is minimally metabolized in the liver and is primarily excreted unchanged in the urine. Its half-life is around 5 to 6 hours, which can be prolonged in individuals with renal impairment.

Contra-indications

• CNS depression
• Comatose states
• Phaeochromocytoma

Adverse effects

• Apathy
• Autonomic dysfunction
• Cardiac arrest
• Cardiovascular effects
• Consciousness impaired
• Corneal opacity
• Epilepsy
• Gastrointestinal disorder
• Glaucoma
• Haemolytic anaemia
• Headache
• Hepatic disorders
• Hyperpyrexia
• Hypersensitivity
• Hyperthermia (dose-related)
• Hypothermia (dose-related)
• Lens opacity
• Menstrual disorder
• Nasal congestion
• Photosensitivity reaction
• Skin reactions
• Urinary hesitation
• Vision blurred
• Withdrawal syndrome

Precautions

• Caution in hepatic impairment
• Caution in renal impairment

Pregnancy

Safety in pregnancy has not been established; caution is advised.

Breast-feeding

It is not known if piracetam is excreted in human milk; caution is advised.

Storage

Store at room temperature, away from light and moisture.

Formulations

• Tablets
• Oral suspension
• Oral solution

Mechanism of action

Piracetam interacts with the polar heads in the phospholipids membrane and the resulting mobile drug-lipid complexes are thought to reorganize the lipids and influence membrane function and fluidity. Such interaction has been reported in a study that investigated the effects of neuronal outgrowth induced by beta amyloid peptides; while amyloid peptides cause lipid disorganization within the cell membranes leading to neuronal death, piracetam demonstrated to decrease the destabilizing effects of amyloid peptide. The authors suggest that piracetam induces a positive curvature of the membrane by occupying the polar groups in the phospholipids to counteract the negative curvature induced by amyloid peptides , which in turn would decrease the likelihood of membrane fusion. This mechanism of action is thought to improve membrane stability, allowing the membrane and transmembrane proteins to maintain and recover the three-dimensional structure or folding for normal function such as membrane transport, chemical secretion, and receptor binding and stimulation. Through restored membrane fluidity, piracetam promotes restored neurotransmission such as glutamatergic and cholinergic systems, enhances neuroplasticity and mediates neuroprotective and anticonvulsant effects at the neuronal level. It is also demonstrated that piracetam also improves the fluidity of platelet membranes. At the vascular level, piracetam decreases adhesion of erythrocytes to cell wall and reduces vasospasm which in turn improves microcirculation including cerebral and renal blood flow. It was found that a drug of the nootropic nature piracetam possessing pronounced antihypoxic properties eliminates calcium chloride-induced disturbances of the cardiac rhythm and significantly raises the threshold of atrial fibrillation during electrical stimulation. The drug's antiarrhythmic effect is followed by a decrease of the rhythm rate and an increase of the contraction amplitude. The animals treated with piracetam in a dose when its antiarrhythmic effects (300 mg/kg) exhibited a decrease of the membrane potential of erythrocytes as compared with control. Similar effects occurred in the animals treated with lidocaine. It can be concluded that in certain types of arrhythmias the use of piracetam restores the normal rhythm of contractions that is perhaps connected with its positive influence on metabolic processes in the myocardium.

Pharmacodynamics

Piracetam is known to mediate various pharmacodynamic actions: **Neuronal effects**: Piracetam modulates the cholinergic, serotonergic, noradrenergic, and glutamatergic neurotransmission although the drug does not display high affinity to any of the associated receptors (Ki >10μM). Instead, piracetam increases the density of postsynaptic receptors and/or restore the function of these receptors through stabilizing the membrane fluidity. In the forebrain of aging mice, the density of NMDA receptors was increased by approximately 20% following 14 days of piracetam treatment. Based on the findings of various animal and human studies, the cognitive processses including learning, memory, attention and consciousness were enhanced from piracetam therapy without inducing sedation and psychostimulant effects. Piracetam mediate neuroprotective effects against hypoxia-induced damage, intoxication, and electroconvulsive therapy. In two studies involving alcohol-treated rats with evidences of withdrawal-related neuronal loss, piracetam was shown to reduce the extent of neuronal loss and increase the numbers of synapses in the hippocampus by up to 20% relative to alcohol-treated or alcohol-withdrawn rats. This suggests that piracetam is capable in promoting neuroplasticity when recoverable neural circuits are present. Although the mechanism of action is not fully understood, administration of piracetam prior to a convulsant stimulus reduces the seizure severity and enhances the anticonvulsant effectiveness of conventional antiepileptics such as carbamazepine and diazepam. **Vascular effects**: Piracetam is shown to increase the deformability of erythrocytes, reduce platelet aggregation in a dose-dependent manner, reduce the adhesion of erythrocytes to vascular endothelium and capillary vasospasm. In healthy volunteers, piracetam mediated a direct stimulant effect on prostacycline synthesis and reduced the plasma levels of fibrinogen and von Willebrand’s factors (VIII: C; VIII R: AG; VIII R: vW) by 30 to 40%. Potentiated microcirculation is thought to arise from a combination of effects on erythrocytes, blood vessels and blood coagulation.