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