4-Bromo-2,5-dimethoxyphenethylamine (2C-B) and structurally related phenylethylamines are potent 5-HT2A receptor antagonists in Xenopus laevis oocytes.
Claudio A Villalobos, Paulina Bull, Patricio Sáez, Bruce K. Cassels, J Pablo Huidobro-Toro
British Journal of Pharmacology April 1, 2004 DOI: 10.1038/sj.bjp.0705722 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Xenopus laevis oocytes microinjected with rat 5-HT2A or 5-HT2C receptor clones |
| Interventions | 2C-I 2C-B 2C-D 2C-H |
| Topics | Serotonin |
| Keywords | Psychoactive compounds Psychoactive effects Phenylethylamines 2c-b Serotonin receptors 5-ht2c type Receptor antagonism Blocking action |
| Citations | 50 |
| Key findings | A series of 2,5-dimethoxy-4-substituted phenylethylamines blocked 5-HT2A but not 5-HT2C receptor-mediated responses in Xenopus laevis oocytes. |
Abstract
1. We recently described that several 2-(2,5-dimethoxy-4-substituted phenyl)ethylamines (PEAs), including 4-I=2C-I, 4-Br=2C-B, and 4-CH(3)=2C-D analogs, are partial agonists at 5-HT(2C) receptors, and show low or even negligible intrinsic efficacy at 5-HT(2A) receptors. These results raised the proposal that these drugs may act as 5-HT(2) antagonists. 2. To test this hypothesis, Xenopus laevis oocytes were microinjected with the rat clones for 5-HT(2A) or 5-HT(2C) receptors. The above-mentioned PEAs and its 4-H analog (2C-H) blocked the 5-HT-induced currents at 5-HT(2A), but not at the 5-HT(2C) receptor, revealing 5-HT(2) receptor subtype selectivity. The 5-HT(2A) receptor antagonism required a 2-min preincubation to attain maximum inhibition. 3. All PEAs tested shifted the 5-HT concentration-response curves to the right and downward. Their potencies varied with the nature of the C(4) substituent; the relative rank order of their 5-HT(2A) receptor antagonist potency was 2C-I>2C-B>2C-D>2C-H. 4. The present results demonstrate that in X. laevis oocytes, a series of 2,5-dimethoxy-4-substituted PEAs blocked the 5-HT(2A) but not the 5-HT(2C) receptor-mediated responses. As an alternative hypothesis, we suggest that the psychostimulant activity of the PEAs may not be exclusively associated with partial or full 5-HT(2A) receptor agonism.
Comparable studies
Other experimental studies on serotonin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action Healthy human volunteers | 1998 | Experimental study | |
| Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin | 2000 | Experimental study | |
| Methylenedioxyamphetamine (MDA) and methylenedioxymethamphetamine (MDMA) cause selective ablation of serotonergic axon terminals in forebrain: immunocytochemical evidence for neurotoxicity Rat brain | 1988 | Experimental study | |
| The molecular mechanism of "ecstasy" [3,4-methylenedioxy-methamphetamine (MDMA)]: serotonin transporters are targets for MDMA-induced serotonin release. Human platelet plasma membrane vesicles and bovine adrenal chromaffin granule membrane... | 1992 | Laboratory study | |
| 5-HT2AReceptor-Mediated Regulation of Brain-Derived Neurotrophic Factor mRNA in the Hippocampus and the Neocortex Rat brain | 1997 | Experimental study |
Citations in the library
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- Metabolism of designer drugs of abuse: an updated review. Current Drug Metabolism June 1, 2010
- Effect fingerprinting of new psychoactive substances (NPS): What can we learn from in vitro data? Pharmacology & Therapeutics February 1, 2018
- Behavioral and neurochemical pharmacology of six psychoactive substituted phenethylamines: mouse locomotion, rat drug discrimination and in vitro receptor and transporter binding and function. Psychopharmacology March 1, 2014
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Cites 8
- Enantiospecific Synthesis and Pharmacological Evaluation of a Series of Super-Potent, Conformationally Restricted 5-HT2A/2C Receptor Agonists Journal of Medicinal Chemistry January 26, 2001
- LSD and DOB: interaction with 5‐HT2A receptors to inhibit NMDA receptor‐mediated transmission in the rat prefrontal cortex European Journal of Neuroscience September 1, 1999
- 2C-B: a new psychoactive phenylethylamine recently discovered in Ecstasy tablets sold on the Swiss black market. Journal of Analytical Toxicology September 1, 1998
- Differences in potency and efficacy of a series of phenylisopropylamine/phenylethylamine pairs at 5-HT(2A) and 5-HT(2C) receptors. British Journal of Pharmacology June 1, 2002
- 5-HT2A receptor-stimulated phosphoinositide hydrolysis in the stimulus effects of hallucinogens. Pharmacology, Biochemistry, and Behavior May 2002
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