Increased affinity and preference of halogenated derivatives of BE 2254 for alpha 1-adrenoceptors demonstrated by functional and binding experiments.

The effects of congeners of BE 2254 (2-[beta-(4'-hydroxyphenyl)-ethyl-aminomethyl]-tetralone), an alpha 1-adrenoceptor antagonist, were compared in functional and binding experiments. In detail, we studied the effects of the compounds on the electrically evoked 3H overflow (alpha 2-adrenoceptor-mediated) and on the evoked contractions (alpha 1-adrenoceptor-mediated) of strips from rabbit pulmonary artery preincubated with [3H]noradrenaline as well as their effects on [3H]yohimbine binding to human platelet membranes (alpha 2-adrenoceptors) and [3H]prazosin binding to rat liver plasma membranes (alpha 1-adrenoceptors). The potencies of the drugs at the presynaptic alpha 2-adrenoceptors of the rabbit pulmonary artery and their affinities for [3H]yohimbine binding sites of human platelets were closely correlated. The same held true for their potencies at the postsynaptic alpha 1-adrenoceptors of the rabbit pulmonary artery and their affinities for [3H]prazosin binding sites of rat hepatic membranes. Compared with the parent compound, the monohalogenated derivatives of BE 2254 (i.e., the 3'-I, 3'-Br, and 3'-Cl analogues) exhibited an even higher affinity (equal to that of prazosin) and a higher selectivity for alpha 1-adrenoceptors (inferior to that of prazosin, but similar to that of corynanthine).