Brexpiprazole is currently under investigation for the treatment of schizophrenia and depression. Using electrophysiology, the present study assessed the in vivo action of brexpiprazole. In the dorsal raphe nucleus, brexpiprazole completely inhibited the firing of serotonin 5-HT neurons via 5-HT1A agonism, and was more potent than aripiprazole, a compound widely used in the clinic. In the locus coeruleus, brexpiprazole reversed the inhibitory effect of the preferential 5-HT2A receptor agonist DOI (2,5-dimethoxy-4-iodoamphetamine) on norepinephrine neuronal firing, demonstrating 5-HT2A antagonistic action. Brexpiprazole reversed the inhibitory effect of the DA agonist apomorphine on ventral tegmental area (VTA) DA neurons, whereas it was ineffective when administered alone, indicating partial agonistic action on D2 receptors. Compared with aripiprazole, which significantly inhibited the firing activity of VTA DA neurons, brexpiprazole displayed less efficacy at D2 receptors. These results provide insight into the in vivo action of brexpiprazole on targets relevant in the treatment of depression and schizophrenia.
See article at J Pharmacol Exp Ther 2014, 351:585–595.
- Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics