Serlin 50 Mechanism of Action

Pharmacology: PHARMACODYNAMICS: Sertraline is a potent and selective inhibitor of neuronal serotonin (5-HT) reuptake in vitro, which results in the potentiation of the effects of 5-HT in animals. It has only very weak effects on norepinephrine and dopamine neuronal reuptake. At clinical doses, sertraline blocks the uptake of serotonin into human platelets. It is devoid of stimulant, sedative or anticholinergic activity or cardiotoxicity in animals. In accord with its selective inhibition of 5-HT uptake, sertraline does not enhance catecholaminergic activity. Sertraline has little affinity for muscarinic (cholinergic), serotonergic, dopaminergic, adrenergic, histaminergic, GABA or benzodiazepine receptors. The chronic administration of sertraline in animals was associated with down-regulation of brain norepinephrine receptors as observed with other clinically effective antidepressants and antiobsessional drugs.
PHARMACOKINETICS: Sertraline exhibits dose proportional pharmacokinetics over the range of 50 to 200 mg. In man, following oral once-daily dosing over the range of 50 to 200 mg for 14 days, peak plasma concentrations (C_max) of sertraline occur at about 4.5 to 8.4 hours post dosing. The mean half life of sertraline for young and elderly men and women ranges from 22-36 hours. Consistent with the terminal elimination half-life, there is an approximately two-fold accumulation up to steady state concentrations, which are achieved after 1 week of once daily dosing. Approximately 98% of the circulating drug is bound to plasma proteins. Animal studies indicate that sertraline has a large apparent volume of distribution. The pharmacokinetics of sertraline in pediatric OCD patients have been shown to be comparable with adults (although pediatric patients metabolize sertraline with slightly greater efficiency). However, lower doses may be advisable for pediatric patients, given their lower body weights (especially those patients 6-12 years), in order to avoid excessive plasma levels. Sertraline undergoes extensive first pass hepatic metabolism. The principal metabolite in plasma, N-desmethylsertraline, is substantially less active (about 20 times) than sertraline in vitro and there is no evidence of activity in in vivo models of depression. The half-life of N-desmethylsertraline is in the range of 62-104 hours. Sertraline and N-desmethylsertraline are both extensively metabolized in man and the resultant metabolites excreted in feces and urine in equal amounts. Only a small amount (<0.2%) of unchanged sertraline is excreted in the urine.