P.2.c.023 Are moclobemide trough concentrations an adequate predictor of the systemic drug exposure

Abstract

Epilepsy is a chronic neurologic disorder which often induces numerous adverse long-term neurologic effects, such as behavioral and cognitive deficits, increased predisposition to additional seizures, and cell injury or death. Cognitive dysfunction, depression, anxiety and sleep disorders are some of the highly prevalent and most disabling complications of epilepsy. The mechanisms that lead to the generation of epileptic comorbidities are poorly understood. Treatment for epileptic complications still remains a challenge because of the poor adherence and drug interactions associated with multi drug prescriptions and also for the fear of worsening seizures by the individual medications for complications. Melatonin, an endogenous hormone secreted by pineal gland has a prominent role in epilepsy. Agomelatine is a novel antidepressant which acts as melatonin MT1 and MT2 receptor agonist and serotonin 5Ht2C receptor antagonist. The combined action at MT1/2 and 5HT2C receptors, reduction in the depolarization-evoked release of glutamate, strong neuroprotective action and possible antioxidant properties of agomelatine could make it a potential agent in the treatment of epilepsy. The effect of agomelatine on hippocampal neuronal cell survival and neurogenesis, neuroprotective effect in hippocampus and frontal cortex and the antioxidant potential may contribute to the protective action of agomelatine against epilepsy induced memory decline. Agomelatine is proven to be an antidepressant and it has relieved anxiety symptoms and improved the quality of sleep in patients with depressive disorder. The action of agomelatine as a melatonin agonist and the consequent circadian resynchronizing property as well as its action as 5-HT2C receptor antagonist, could possibly suggest an antidepressant and anxiolytic action of agomelatine in epilepsy induced depressive behavior and anxiety. Since one of the many causes of sleep disruption in epilepsy is circadian rhythm disturbances and sleep promoting and circadian effects of melatonin is attributed to the MT1and MT2 subtypes of human melatonin receptors, agomelatine may also have a promising effect on epilepsy induced sleep disruptions. Thus with all these potential pharmacological actions, agomelatine could be recommended as a potential drug to treat epilepsy and its complications.