Tag: 5-HT2

What is Quipazine?

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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-HT2A receptor agonist, ligand of the serotonin 5-HT2B and 5-HT2C 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-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.

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.

This page is based on the copyrighted Wikipedia article < https://en.wikipedia.org/wiki/Quipazine >; it is used under the Creative Commons Attribution-ShareAlike 3.0 Unported License (CC-BY-SA). You may redistribute it, verbatim or modified, providing that you comply with the terms of the CC-BY-SA.

What is a Serotonin-Dopamine Releasing Agent?

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Introduction

A serotonin–dopamine releasing agent (SDRA) is a type of drug which induces the release of serotonin and dopamine in the body and/or brain.

A closely related type of drug is a serotonin–dopamine reuptake inhibitor (SDRI).

Examples of SDRAs

A number of tryptamine derivatives have been found to act as SDRAs. One such agent is 5-chloro-αMT (PAL-542), which has been reported as having about 64-fold selectivity for dopamine release over norepinephrine release and about 3-fold selectivity for serotonin release over dopamine release, making it a highly selective and well-balanced SDRA. Another agent is 5-fluoro-αET (PAL-545), which has about 35-fold selectivity for dopamine release over norepinephrine release and about 4-fold selectivity for serotonin release over dopamine release. Though selective for inducing the release of serotonin and dopamine over norepinephrine, these agents are not selective monoamine releasers; they have all also been found to be potent agonists of the 5-HT2A receptor, and may act as agonists of other serotonin receptors as well.

UWA-101 is an SDRI that, based on its chemical structure, may also have a great efficacy as a releasing agent of serotonin and dopamine.

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What is a Serotonin Releasing Agent?

Published on by Andrew Marshall3 Comments

Introduction

A serotonin releasing agent (SRA) is a type of drug that induces the release of serotonin into the neuronal synaptic cleft. A selective serotonin releasing agent (SSRA) is an SRA with less significant or no efficacy in producing neurotransmitter efflux at other types of monoamine neurons.

SSRAs have been used clinically as appetite suppressants, and they have also been proposed as novel antidepressants and anxiolytics with the potential for a faster onset of action and superior efficacy relative to the selective serotonin reuptake inhibitors (SSRIs).

A closely related type of drug is a serotonin reuptake inhibitor (SRI).

Examples and Use of SRAs

Amphetamines like MDMA, MDEA, MDA, and MBDB, among other relatives, are recreational drugs termed entactogens. They act as serotonin-norepinephrine-dopamine releasing agents (SNDRAs) and also agonise serotonin receptors such as those in the 5-HT2 subfamily. Fenfluramine, chlorphentermine, and aminorex, which are also amphetamines and relatives, were formerly used as appetite suppressants but were discontinued due to concerns of cardiac valvulopathy. This side effect has been attributed to their additional action of potent agonism of the 5-HT2B receptor. The designer drug 4-methylaminorex, which is an SNDRA and 5-HT2B agonist, has been reported to cause this effect as well.

Many tryptamines, such as DMT, DET, DPT, DiPT, psilocin, and bufotenin, are SRAs as well as non-selective serotonin receptor agonists. These drugs are serotonergic psychedelics, which is a consequence of their ability to activate the 5-HT2A receptor. αET and αMT, also tryptamines, are SNDRAs and non-selective serotonin receptor agonists that were originally thought to be monoamine oxidase inhibitors and were formerly used as antidepressants. They have since been discontinued and are now encountered solely as recreational drugs.

Indeloxazine is an SRA and norepinephrine reuptake inhibitor that was formerly used as an antidepressant, nootropic, and neuroprotective.

List of SSRAs

Pharmaceutical Drugs

  • Chlorphentermine (Apsedon, Desopimon, Lucofen)
  • Cloforex (Oberex) (prodrug of chlorphentermine)
  • Dexfenfluramine (Redux) (enantiomer of fenfluramine)
  • Etolorex (prodrug of chlorphentermine; never marketed)
  • Fenfluramine (Pondimin, Fen-Phen)
  • Flucetorex (related to chlorphentermine; never marketed)
  • Indeloxazine (Elen, Noin) (non-selective; discontinued)
  • Levofenfluramine (enantiomer of fenfluramine)
  • Carbamazepine (Equetro, Epitol, and many other variations)

Research Chemicals

  • Amiflamine (FLA-336)
  • Viqualine (PK-5078)
  • 2-Methyl-3,4-methylenedioxyamphetamine (2-Methyl-MDA)
  • 3-Methoxy-4-methylamphetamine (MMA)
  • 3-Methyl-4,5-methylenedioxyamphetamine (5-Methyl-MDA)
  • 3,4-Ethylenedioxy-N-methylamphetamine (EDMA)
  • 4-Methoxyamphetamine (PMA)
  • 4-Methoxy-N-ethylamphetamine (PMEA)
  • 4-Methoxy-N-methylamphetamine (PMMA)
  • 4-Methylthioamphetamine (4-MTA)
  • 5-(2-Aminopropyl)-2,3-dihydrobenzofuran (5-APDB)
  • 5-Indanyl-2-aminopropane (IAP)
  • 5-Methoxy-6-methylaminoindane (MMAI)
  • 5-Trifluoromethyl-2-aminoindane (TAI)
  • 5,6-Methylenedioxy-2-aminoindane (MDAI)
  • 5,6-Methylenedioxy-N-methyl-2-aminoindane (MDMAI)
  • 6-Chloro-2-aminotetralin (6-CAT)
  • 6-Tetralinyl-2-aminopropane (TAP)
  • 6,7-Methylenedioxy-2-aminotetralin (MDAT)
  • 6,7-Methylenedioxy-N-methyl-2-aminotetralin (MDMAT)
  • N-Ethyl-5-trifluoromethyl-2-aminoindane (ETAI)
  • 6-(2-aminopropil)benzofurans (6-APB)
  • 5-(2-aminopropyl)benzofuran (5-APB)

This page is based on the copyrighted Wikipedia article < https://en.wikipedia.org/wiki/Serotonin_releasing_agent >; it is used under the Creative Commons Attribution-ShareAlike 3.0 Unported License (CC-BY-SA). You may redistribute it, verbatim or modified, providing that you comply with the terms of the CC-BY-SA.

An Overview of the 5-HT2 Receptor

Published on by Andrew Marshall30 Comments

Introduction

The 5-HT2 receptors are a subfamily of 5-HT receptors that bind the endogenous neurotransmitter serotonin (5-hydroxytryptamine, 5-HT).

Outline

The 5-HT2 subfamily consists of three G protein-coupled receptors (GPCRs) which are coupled to Gq/G11 and mediate excitatory neurotransmission, including:

  • 5-HT2A
  • 5-HT2B
  • 5-HT2C

This page is based on the copyrighted Wikipedia article < https://en.wikipedia.org/wiki/5-HT2_receptor >; it is used under the Creative Commons Attribution-ShareAlike 3.0 Unported License (CC-BY-SA). You may redistribute it, verbatim or modified, providing that you comply with the terms of the CC-BY-SA.