Quipazine

Pharmacodynamics

Quipazine is a serotonin 5-HT₃ receptor agonist and to a lesser extent a serotonin 5-HT_2A, 5-HT_2B, and 5-HT_2C 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-HT_1B receptor and to a lesser extent the serotonin 5-HT_1A 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-HT_2A receptor, as they are blocked by serotonin 5-HT_2A 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-HT_2A 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-HT_2A 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]

In addition to its psychedelic-like effects, quipazine can produce antiaggressive effects in rodents.^[28] It can also 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.^[29][30] 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.^[29][30] 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.^[31] Fenfluramine has been found to fully generalize to quipazine, but levofenfluramine, in contrast to quipazine, did not generalize to dextroamphetamine.^[29][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-HT_2C receptor over the serotonin 5-HT_2A receptor.^[4]

Quipazine is a very weak agonist of the human trace amine-associated receptor 1 (TAAR1).^[21]

Synthesis

Quipazine is synthesized by reacting 2-chloroquinoline with piperazine.^[33]

Legal status