Aripiprazole has both agonistic and antagonistic effects on the dopaminergic system in endocrinological challenge tests

Abstract

Aripiprazole, a novel antipsychotic agent, acts as a partial agonist at dopamine D2 receptors and at serotonin 5-HT1A receptors, and as a potent antagonist at 5-HT2A receptors. In the present study, 24 healthy male subjects were included after written informed consent. In a randomized placebo-controlled double-blind study, the volunteers were treated for 2 weeks either with placebo or with aripiprazole (15mg daily). Before and after the 2-week treatment period, a low-dose apomorphine test (0.005mg/kg s.c.) and a low-dose haloperidol test (0.5mg i.v.) were performed. Hormonal parameters (ACTH, cortisol, GH [growth hormone], prolactin) were determined in each test. In the placebo group (n=12), the GH response to the dopamine agonist apomorphine and the prolactin response to the dopamine antagonist haloperidol remained unchanged. However, in participants treated with aripiprazole (n=12) both the apomorphine-induced GH stimulation and the haloperidol-induced prolactin response were significantly reduced. No significant effects were seen with regard to ACTH and cortisol. Apparently, aripiprazole acts as a dopamine antagonist under hyperdopaminergic conditions (apomorphine test) blocking the dopaminergic stimulation of GH and also as a dopamine agonist in a hypodopaminergic situation (haloperidol test) antagonizing the antidopaminergic disinhibition of prolactin release. Using this endocrinological challenge paradigm, aripiprazole seems to be a dopamine system stabilizer.