α-adrenoceptor occupancy by N,N-dimethyl-2-bromo-2-phenethylamine hydrobromide (DMPEA) in rat vas deferens

Abstract

The effects of N,N-dimethyl-2-bromo-2-phenethylamine hydrobromide (DMPEA) on α 1- and α 2-adrenoceptors were examined in the isolated rat vas deferens. The active species of DMPEA was the corresponding ethyleniminium ion, which forms in the biophase, since pretreatment of tissues with sodium thiosulphate completely prevented the DMPEA-induced inhibition at α 1- and α 2-adrenoceptors. DMPEA was approximately 42-fold more potent in inhibiting α 2-adrenoceptors than it was in inhibiting α 1-adrenoceptors. The antagonism of both receptor types was reversible since washing of the tissues after incubation with DMPEA brought the agonist dose-response curve back to the control value. At α 1-adrenoceptors, DMPEA displaced the noradrenaline dose-response curve to the right and concomitantly depressed the maximum response, effects which are consistent with a non-competitive mechanism of action. At α 2-adrenoceptors, DMPEA caused a parallel shift of the clonidine or noradrenaline dose-response curve to the right in field-stimulated prostatic portions of the rat vas deferens. The antagonism appeared to be competitive at low concentrations, whereas the shift of the clonidine dose-response curve at higher concentrations became overproportional to the DMPEA concentration. A combination of DMPEA with idazoxan produced a less-than-additive shift of the dose-response curve for clonidine, indicating that these antagonists do not bind to the same site.