Pirenperone (, , ; developmental code names R-47456 and R-50656) is a serotonin receptor antagonist closely related to ketanserin and risperidone which is described as an antipsychotic and tranquilizer and was never marketed.
It is a relatively selective antagonist of the serotonin 5-HT<sub>2A</sub> receptor and has been used in scientific research to study the serotonin system. Its affinities (K<sub>i</sub>) for serotonin and other receptors have been reported to be 0.3 to 1.1nM for the serotonin 5-HT<sub>2A</sub> receptor, 6.5nM for the serotonin 5-HT<sub>7</sub> receptor, 20nM for the ñ<sub>1B</sub>-adrenergic receptor, 20nM for the ñ<sub>2B</sub>-adrenergic receptor, 61nM for the serotonin 5-HT<sub>2B</sub> receptor, 60 to 77nM for the serotonin 5-HT<sub>2C</sub> receptor, 485 to 1,700nM for the serotonin 5-HT<sub>1A</sub> receptor, and >1,000 or 6,600nM for the serotonin 5-HT<sub>1B</sub> receptor, whereas other receptors were not reported.
The elimination half-life of pirenperone has been said to be 4 to 6hours.
In the 1980s, the drug was found to block the effects of the lysergic acid diethylamide (LSD) in animals, and, along with ketanserin, led to the elucidation of the 5-HT<sub>2A</sub> receptor as the biological mediator of the effects of serotonergic psychedelics. Along similar lines, there has been interest in pirenperone for potential use as a trip killer against psychedelics in humans.