INCREASED AFFINITY AND PREFERENCE OF HALOGENATED DERIVATIVES OF BE-2254 FOR ALPHA-1-ADRENOCEPTORS DEMONSTRATED BY FUNCTIONAL AND BINDING EXPERIMENTS

  • 1 January 1984
    • journal article
    • research article
    • Vol. 6  (6) , 1238-1244
Abstract
The effects of congeners of BE 2254 (2-[.beta.-(4''-hydroxyphenyl)ethylaminomethyl]tetralone), an .alpha.1-adrenoceptor antagonist, were compared in functional and binding experiments. 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 [norepinephrine] 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) were studied. 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 analogs) 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).