Introduction

Quipazine, also known as 1-(2-quinolinyl)piperazine, is a serotonergic drug of the arylpiperazine family and an analogue of 1-(2-pyridinyl)piperazine which is used in scientific research.

It was first described in the 1960s and was originally intended as an antidepressant but was never developed or marketed for medical use.

Pharmacology

Pharmacodynamics

Quipazine is a serotonin 5-HT₃ receptor agonist and to a lesser extent a serotonin 5-HT_2A receptor agonist, ligand of the serotonin 5-HT_2B and 5-HT_2C 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-HT_2A receptor, as they are blocked by serotonin 5-HT_2A receptor antagonists like ketanserin. The head twitches induced by quipazine are potentiated by the monoamine oxidase inhibitor (MAOI) pargyline. Based on this, it has been suggested that quipazine may act as a serotonin releasing agent and that it may induce the head twitch response by a dual action of serotonin 5-HT_2A receptor agonism and induction of serotonin release.

Quipazine did not produce psychedelic effects in humans up to a dose of 25 mg, 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.

Although quipazine does not generalise to dextroamphetamine in drug discrimination tests of dextroamphetamine-trained rodents, dextroamphetamine and cathinone have been found to partially generalise to quipazine in assays of quipazine-trained rodents. In relation to this, it has been suggested that quipazine might possess some dopaminergic activity, as the discriminative stimulus properties of amphetamine appear to be mediated by dopamine signalling. Relatedly, quipazine has been said to act as a dopamine receptor agonist in addition to serotonin receptor agonist. Conversely however, the generalisation may be due to serotonergic activities of amphetamine and cathinone. Fenfluramine has been found to fully generalise to quipazine, but levofenfluramine, in contrast to quipazine, did not generalise to dextroamphetamine.

Chemistry

Quipazine is a substituted piperazine and quinoline.

It is structurally related to 6-nitroquipazine and 1-(1-naphthyl)piperazine.

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