Ritanserin is an Orally Active and Long Acting of 5-HT2 Receptor Antagonist

5-HT receptors (Serotonin receptors) are a group of G protein-coupled receptors (GPCRs) and ligand-gated ion channels (LGICs) found in the central and peripheral nervous systems. They mediate both excitatory and inhibitory neurotransmission. There are many types of 5-HT receptors: 5-HT1, 5-HT2, 5-HT3, 5-HT4, 5-HT5, 5-HT6, and 5-HT7 receptors. In addition, 5-HT receptors influence various biological and neurological processes such as aggression, anxiety, appetite, cognition. Among them, 5-HT2 receptors bind the endogenous neurotransmitter serotonin. The 5-HT2 subfamily consists of three G protein-coupled receptors (GPCRs), including 5-HT2A, 5-HT2B, and 5-HT2C.

Ritanserin (also known as R 55667) is a highly potent, relatively selective, orally active, long acting 5-HT2 receptor antagonist. However, this compound shows less active on histamine H1, dopamine D2, adrenergic α1, adrenergic α2, and 5-HT1 receptors. In in vitro binding assays, Ritanserin displays high affinity binding to serotonin-S2 sites in rat frontal cortex tissue. In addition, Ritanserin dissociates very slowly from 5-HT2 receptor  (t1/2 of 160 min) and rapidly from dopamine-D2 sites (t1/2 of 11 min). Importantly, Ritanserin has anxiolytic, antidepressant, antiparkinsonian, and antihypertensive effects. It has an additional intrinsic antidopaminergic effect. Moreover, Ritanserin reduces cocaine cravings and/or cocaine use. Furthermore, Ritanserin is also a competitive noradrenaline antagonist, and then it decreases the mean arterial blood pressure of anaesthetized rats. Moreover, Ritanserin blocked CaV1.2 channel currents in a concentration-dependent manner, causing vasodilation in vitro.

To sum up, Ritanserin is a potent, orally active, and long acting 5-HT2 receptor antagonist, with anxiolytic, antidepressant, and antihypertensive effects.


[1] Leysen JE, et al. Mol Pharmacol. 1985 Jun;27(6):600-11.

[2] Fabio Fusi, et al. Acta Pharmacol Sin. 2020 Sep;41(9):1158-1166.