# Quipazine

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. 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 activities :
| Target | Affinity (K$_i$, nM) |
| 5-HT$_{1A}$ | 230–>10,000 |
| 5-HT$_{1B}$ | 1,000 |
| 5-HT$_{1D}$ | 1,000–3,720 |
| 5-HT$_{1E}$ | ND |
| 5-HT$_{1F}$ | ND |
| 5-HT$_{2A}$ | 59–2,780 |
| 5-HT$_{2B}$ | 49–178 |
| 5-HT$_{2C}$ | 54–339 |
| 5-HT$_3$ | 2.0–4.0 (K$_i$) 1.0 (EC$_{50}$Tooltip half-maximal effective concentration) |
| 5-HT$_4$ | >10,000 (guinea pig) |
| 5-HT$_{5A}$ | >10,000 (mouse) |
| 5-HT$_6$ | 3,600 |
| 5-HT$_7$ | 3,033 |
| α$_1$ | >10,000 (rat) |
| α$_2$ | 5,000 (rat) |
| β$_1$ | 5,600 |
| β$_2$ | 2,900 (rat) |
| D$_1$ | >10,000 |
| D$_2$ | >10,000 |
| D$_2$-like | 3,920 (rat) |
| mAChTooltip Muscarinic acetylcholine receptor | >10,000 (rat) |
| SERTTooltip Serotonin transporter | 30 |
| NETTooltip Norepinephrine transporter | ND |
| DATTooltip Dopamine transporter | ND |
| Notes: The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise specified. Refs: ||
Quipazine is a serotonin 5-HT$_3$ 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-HT$_3$ 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-HT$_3$ 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-HT$_3$ receptors using the serotonin 5-HT$_3$ receptor antagonist ondansetron.
Quipazine can produce tachycardia, including positive chronotropic and positive inotropic effects, through activation of the serotonin 5-HT$_3$ 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.

## 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).

### Synthesis

It is synthesized by reacting 2-chloroquinoline with piperazine.