The therapeutic effect of aripiprazole in schizophrenia is due to a combination of partial agonist activity against D2-dopamine and 5HT1a-serotonin receptors and antagonistic activity against 5HT2 serotonin receptors.
Aripiprazole has a high in vitro affinity for D2- and D3-dopamine receptors, 5HT1a- and 5HT2a-serotonin receptors, and a moderate affinity for D4-dopamine, 5HT2c- and 5HT7-serotonin receptors, a1-adrenoceptors and 1-adrenoceptors. Aripiprazole is also characterized by a moderate affinity for the serotonin reuptake sites and a lack of affinity for muscarinic receptors. Aripiprazole in animal experiments showed antagonism against dopaminergic hyperactivity and agonism against dopaminergic hypoactivity. Not only dopamine and serotonin receptors can interact with some of the clinical effects of aripiprazole.
The activity of the drug is due to the active substance – aripiprazole. The average half-life of aripiprazole is approximately 75 hours. The equilibrium concentration is reached after 14 days. Cumulation of the drug with repeated administration is predictable. Pharmacokinetics of aripiprazole at steady state are dose proportional. No daily fluctuations in the distribution of aripiprazole and its metabolite of dehydroaripiprazole were noted. It has been established that the major metabolite in human blood plasma, dehydroaripiprazole, has the same affinity for D2-dopamine receptors as aripiprazole.