Quipazine is a serotonergic drug of the arylpiperazine group which is used in scientific research. It was first described in the 1960s and was originally intended as an antidepressant but was never developed for medical use.

Pharmacology

Pharmacodynamics

Quipazine is a serotonin 5-HT3 receptor agonist and to a lesser extent a serotonin 5-HT2A receptor agonist, ligand of the serotonin 5-HT2B and 5-HT2C receptors, and serotonin reuptake inhibitor. Activation of the serotonin 5-HT3 is implicated in inducing nausea and vomiting as well as anxiety, which has limited the potential clinical usefulness of quipazine. Quipazine produces a head-twitch response and other psychedelic-consistent effects in animal studies including in mice, rats, and monkeys. These effects appear to be mediated by activation of the serotonin 5-HT2A receptor, as they are blocked by serotonin 5-HT2A receptor antagonists like ketanserin. Quipazine did not produce psychedelic effects in humans up to a dose of 25mg, which was the highest dose tested due to serotonin 5-HT3 receptor-mediated side effects of nausea and gastrointestinal discomfort. Alexander Shulgin has anecdotally claimed that a fully effective psychedelic dose could be reached by blocking serotonin 5-HT3 receptors using the serotonin 5-HT3 receptor antagonist ondansetron. Quipazine can produce tachycardia, including positive chronotropic and positive inotropic effects, through activation of the serotonin 5-HT3 receptor.

Chemistry

Quipazine is a substituted piperazine and quinoline. It is structurally related to 6-nitroquipazine. It is synthesized by reacting 2-chloroquinoline with piperazine.