Quipazine

Use and effects

The effects and side effects of quipazine in humans have been described. At a dose of 25mg orally, they included nausea, flatulence, gastrointestinal discomfort, and diarrhea, with no LSD-like subjective effects. Higher doses were not assessed due to serotonin 5-HT3 receptor-mediated side effects of nausea and gastrointestinal discomfort. An anecdotal report in one or more subjects, in which the dose of quipazine was said to be 0.5mg (sic), described quipazine as producing low-dose mescaline-like effects followed by onset of dysphoria and nausea.

It was suggested by Jerrold C. Winter in 1994 that serotonin 5-HT3 receptor antagonists like ondansetron could allow for use of higher doses of quipazine and assessment of whether it produces clear psychedelic effects or not. Alexander Shulgin subsequently reported in The Shulgin Index (2011), based on an anonymous report dated to 2007, that quipazine in combination with a serotonin 5-HT3 receptor antagonist, presumably ondansetron, produced a "full psychedelic response".

Interactions

Serotonin 5-HT3 receptor antagonists like ondansetron have been reported to block the nausea and vomiting induced by quipazine. Serotonin 5-HT2A receptor antagonists like ketanserin have been reported to block the psychedelic-like effects of quipazine in animals.

Pharmacology

Pharmacodynamics

Quipazine is a serotonin 5-HT3 receptor agonist and to a lesser extent a serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptor agonist as well as serotonin reuptake inhibitor. It also shows affinity for serotonin 5-HT1 receptors, including the serotonin 5-HT1B receptor and to a lesser extent the serotonin 5-HT1A receptor. 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. 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-HT2A receptor agonism and induction of serotonin release.

Besides the head-twitch response, quipazine fully substitutes for LSD and partially substitutes for mescaline in rodent drug discrimination tests. In addition, quipazine substitutes for DOM in rodents and monkeys and this is blocked by serotonin 5-HT2A receptor antagonists like pizotyline and ketanserin. When quipazine is used as the training drug, LSD, mescaline, and psilocybin all fully substitute for quipazine. In monkeys, quipazine additionally produced LSD-like behavioral changes along with projectile vomiting. In contrast to primates, rodents generally lack an emetic response, and hence the nausea and vomiting that quipazine can induce may not be a limiting factor in this order of animals. Similarly to DOI, quipazine alters time perception in rodents.

In addition to its psychedelic-like effects, quipazine can produce antiaggressive effects in rodents. It can also produce tachycardia, including positive chronotropic and positive inotropic effects, through activation of the serotonin 5-HT3 receptor.

Although quipazine does not generalize to dextroamphetamine in drug discrimination tests of dextroamphetamine-trained rodents, dextroamphetamine and cathinone have been found to partially generalize 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 signaling. Relatedly, quipazine has been said to act as a dopamine receptor agonist in addition to serotonin receptor agonist. Conversely however, the generalization may be due to serotonergic activities of amphetamine and cathinone. Fenfluramine has been found to fully generalize to quipazine, but levofenfluramine, in contrast to quipazine, did not generalize to dextroamphetamine.

Quipazine is said to differ in its pharmacology and effects from other serotonergic arylpiperazines like TFMPP and mCPP. Relatedly, unlike quipazine, neither TFMPP nor mCPP substitute for DOM in drug discrimination tests. In addition, DOM and TFMPP mutually antagonize each others' stimulus effects. In contrast to quipazine, TFMPP and mCPP show prominent bias or preference for the serotonin 5-HT2C receptor over the serotonin 5-HT2A receptor.

Quipazine is a very weak agonist of the human trace amine-associated receptor 1 (TAAR1).

Chemistry

Quipazine is a substituted piperazine and quinoline. It is structurally related to 6-nitroquipazine, isoquipazine, 1-(2-naphthyl)piperazine (2-NP), and 1-(1-naphthyl)piperazine (1-NP).

Novel analogues of quipazine with retained serotonin 5-HT2A receptor agonism and reduced undesirable off-target activity such as serotonin 5-HT3 receptor agonism and associated adverse effects have been developed and characterized. A doctoral thesis on novel psychedelic quipazine analogues was published by Yilun Yang at Columbia University in August 2025. However, the thesis is embargoed until 2030.

Synthesis

Quipazine is synthesized by reacting 2-chloroquinoline with piperazine.

History

Quipazine was first described in the scientific literature by 1966. It was described as an antidepressant-like agent by 1971. The psychedelic-like effects of quipazine in animals were first described by 1977.

Society and culture

Legal status

Canada

Quipazine is not a controlled substance in Canada as of 2025.

United States

Quipazine is not an explicitly controlled substance in the United States.

References

References

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