Volinanserin (MDL100907) (MDL 100907) is a potent and selective antagonist of the serotonin receptor 5-HT2 (Ki: 0.36 nM) and shows 300-fold selectivity for 5-HT2 receptor over 5-HT1c, alpha-1 adrenergic and sigma receptors.

5-HT2 receptor:0.36 nM (Ki)

Volinanserindemonstrated low nanomolar or subnanomolar binding in vitro at the 5-HT2A receptor and showed a > 100-fold separation from all other receptors measured. Volinanserinhad subnanomolar potency as a 5-HT2A antagonist in vitro in reversing 5-HT-stimulated inositol phosphate accumulation in NIH 3T3 cells transfected with the rat 5-HT2A receptor [2].

In mice, Volinanserinblocked amphetamine-stimulated locomotion at doses that did not significantly affect apomorphine-stimulated climbing behavior. When administered chronically, Volinanserinselectively reduced the number of spontaneously active A10 neurons [1]. In vivo, Volinanserinpotently inhibited 5-methoxy-N, N-dimethyltryptamine-induced head twitches in mice or 5-hydroxytryptophan-induced head twitches in rats. In vivo, functional tests in mice revealed a > 500-fold separation between doses that produced 5-HT2A antagonism and doses that produced alpha 1-adrenergic or striatal D2 antagonism [2].