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Quipazine
Chemical compound From Wikipedia, the free encyclopedia
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Quipazine, also known as 1-(2-quinolinyl)piperazine (2-QP), is a serotonergic drug of the arylpiperazine family and an analogue of 1-(2-pyridinyl)piperazine which is used in scientific research.[2][3][4][5][6] It was first described in the 1960s and was originally intended as an antidepressant but was never developed or marketed for medical use.[2][7][5] The effects of quipazine in humans include nausea, vomiting, gastrointestinal disturbances, diarrhea, and, at higher doses, psychedelic effects.[2][1][4] Quipazine may represent the prototype of a novel structural class of psychedelic drugs.[2][8][9]
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Effects
The effects and side effects of quipazine in humans have been described.[1][2] At a dose of 25 mg orally, they included nausea, flatulence, gastrointestinal discomfort, and diarrhea, with no LSD-like subjective effects.[1] Higher doses were not assessed due to serotonin 5-HT3 receptor-mediated side effects of nausea and gastrointestinal discomfort.[1][4] An anecdotal report in one or more subjects, in which the dose of quipazine was said to be 0.5 mg (sic), described quipazine as producing low-dose mescaline-like effects followed by onset of dysphoria and nausea.[1][2][10]
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.[1] 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".[4][11][2][12]
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Interactions
Serotonin 5-HT3 receptor antagonists like ondansetron have been reported to block the nausea and vomiting induced by quipazine.[4][11][2][12] Serotonin 5-HT2A receptor antagonists like ketanserin have been reported to block the psychedelic-like effects of quipazine in animals.[2][4]
Pharmacology
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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.[2][3][17][14][15] 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.[22] 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.[2][3][4]
Quipazine produces a head-twitch response and other psychedelic-consistent effects in animal studies including in mice, rats, and monkeys.[2][4][23][24][25] 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.[2][4][25] The head twitches induced by quipazine are potentiated by the monoamine oxidase inhibitor (MAOI) pargyline.[25][26] 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.[25][26]
Besides the head-twitch response, quipazine fully substitutes for LSD and partially substitutes for mescaline in rodent drug discrimination tests.[1] In addition, quipazine substitutes for DOM in rodents and monkeys and this is blocked by serotonin 5-HT2A receptor antagonists like pizotyline and ketanserin.[2] When quipazine is used as the training drug, LSD, mescaline, and psilocybin all fully substitute for quipazine.[2] In monkeys, quipazine additionally produced LSD-like behavioral changes along with projectile vomiting.[1] 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.[2] Similarly to DOI, quipazine alters time perception in rodents.[27]
Quipazine can produce tachycardia, including positive chronotropic and positive inotropic effects, through activation of the serotonin 5-HT3 receptor.[3]
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.[28][29] 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.[28][29] Relatedly, quipazine has been said to act as a dopamine receptor agonist in addition to serotonin receptor agonist.[25] Conversely however, the generalization may be due to serotonergic activities of amphetamine and cathinone.[30] Fenfluramine has been found to fully generalize to quipazine, but levofenfluramine, in contrast to quipazine, did not generalize to dextroamphetamine.[28][24]
Quipazine is said to differ in its pharmacology and effects from other serotonergic arylpiperazines like TFMPP and mCPP.[2][4] Relatedly, unlike quipazine, neither TFMPP nor mCPP substitute for DOM in drug discrimination tests.[2][4] In addition, DOM and TFMPP mutually antagonize each others' stimulus effects.[2] In contrast to quipazine, TFMPP and mCPP show prominent bias or preference for the serotonin 5-HT2C receptor over the serotonin 5-HT2A receptor.[4]
Quipazine is a very weak agonist of the human trace amine-associated receptor 1 (TAAR1).[21]
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Chemistry
Quipazine is a substituted piperazine and quinoline.[5] It is structurally related to 6-nitroquipazine, isoquipazine, 1-(2-naphthyl)piperazine (2-NP), and 1-(1-naphthyl)piperazine (1-NP).[5][4]
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.[8][9]
Synthesis
Quipazine is synthesized by reacting 2-chloroquinoline with piperazine.[31]
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History
Quipazine was first described in the scientific literature by 1966.[5][32] It was described as an antidepressant-like agent by 1971.[7] The psychedelic-like effects of quipazine in animals were first described by 1977.[26]
See also
References
External links
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