Artículos de revistas
4-Bromo-2,5-dimethoxyphenethylamine (2C-B) and structurally related phenylethylamines are potent 5-HT2A receptor antagonists in Xenopus laevis oocytes
Fecha
2004-02-04Registro en:
British Journal of Pharmacology, Vol. 141, p. 1167–1174, 2004.
1476-5381
Autor
Villalobos, Claudio A.
Bull, Paulina
Sáez, Patricio
Cassels Niven, Bruce
Huidobro Toro, Juan Pablo
Institución
Resumen
1 We recently described that several 2-(2,5-dimethoxy-4-substituted phenyl)ethylamines (PEAs),
including 4-I¼2C-I, 4-Br¼2C-B, and 4-CH3¼2C-D analogs, are partial agonists at 5-HT2C
receptors, and show low or even negligible intrinsic efficacy at 5-HT2A receptors. These results raised
the proposal that these drugs may act as 5-HT2 antagonists.
2 To test this hypothesis, Xenopus laevis oocytes were microinjected with the rat clones for 5-HT2A or
5-HT2C receptors. The above-mentioned PEAs and its 4-H analog (2C-H) blocked the 5-HT-induced
currents at 5-HT2A, but not at the 5-HT2C receptor, revealing 5-HT2 receptor subtype selectivity. The
5-HT2A 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-HT2A
receptor antagonist potency was 2C-I42C-B42C-D42C-H.
4 The present results demonstrate that in X. laevis oocytes, a series of 2,5-dimethoxy-4-substituted
PEAs blocked the 5-HT2A but not the 5-HT2C 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-HT2A receptor agonism