Brexpiprazole-d8

Brexpiprazole-d₈ is intended for use as an internal standard for the quantification of brexpiprazole by GC- or LC-MS. Brexpiprazole is a serotonin (5-HT) and dopamine receptor modulator that has high affinity (K_i = <1 nM) for 5-HT_1A and 5-HT_2A serotonin, dopamine D_2L, and α_1B-, and α_2C-adrenergic receptors in CHO cell membranes expressing the human receptors.¹ It acts as a partial agonist of 5-HT_1A, D_2L, and D₃ receptors (EC₅₀s = 0.49, 4.0, and 2.8 nM, respectively) and an antagonist of 5-HT_2A, 5-HT_2B, as well as α_1B- and α_2C-adrenergic receptors (IC₅₀s = 6.5, 14, 0.66, and 63 nM, respectively) in vitro. In vivo, brexpiprazole dose-dependently reduces conditioned avoidance response (CAR) time, inhibits locomoter hyperactivity induced by apomorphine and amphetamine, and reverses cognitive defects induced by subchronic PCP administration in rats.² It also reduces apomorphine-induced eye blinking in cynomolgus monkeys. Formulations containing brexpiprazole have been used in the treatment of schizophrenia and major depressive disorder.

1.Maeda, K., Sugino, H., Akazawa, H., et al.Brexpiprazole I: In vitro and in vivo characterization of a novel serotonin-dopamine activity modulatorJ. Pharmacol. Exp. Ther.350(3)589-604(2014) 2.Maeda, K., Lerdrup, L., Sugino, H., et al.Brexpiprazole II: Antipsychotic-like and procognitive effects of a novel serotonin-dopamine activity modulatorJ. Pharmacol. Exp. Ther.350(3)605-614(2014)