4-Bromo-2,5-dimethoxyphenethylamine (2C-B) and structurally related phenylethylamines are potent 5-HT 2A receptor antagonists in Xenopus laevis oocytes

Villalobos C. A.; Huidobro-Toro J.P.; Bull, P; Saez P.; Cassels, B.K.

Keywords: animals, serotonin, binding, rats, cell, structure, 2a, laevis, receptor, time, methyl, xenopus, nitro, oocytes, female, drug, molecular, antagonism, microinjections, article, antagonist, activity, oocyte, phenethylamine, concentration, potency, incubation, controlled, animal, study, 4, phenethylamines, response, relationship, derivative, priority, nonhuman, journal, Structure-Activity, 2,5, Receptor,, unclassified, Cloning,, bromo, Serotonin,, iodo, 2C, 5-HT2A, 5-HT2C, dimethoxyphenylethylamine, dimethoxyphenethylamine

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.

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Título de la Revista: BRITISH JOURNAL OF PHARMACOLOGY
Volumen: 141
Número: 7
Editorial: Wiley
Fecha de publicación: 2004
Página de inicio: 1167
Página final: 1174
URL: http://www.scopus.com/inward/record.url?eid=2-s2.0-2342530990&partnerID=q2rCbXpz