title: Increased affinity and preference of halogenated derivatives of BE 2254 for alpha 1-adrenoceptors demonstrated by functional and binding experiments.
abstract: 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).
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000378:metabolism*; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism; D010627:Phenethylamines / Q000378:metabolism / Q000494:pharmacology*; D011224:Prazosin / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D044024:Tetralones; D015016:Yohimbine / Q000378:metabolism
chemical_list: D000317:Adrenergic alpha-Antagonists; D010627:Phenethylamines; D011942:Receptors, Adrenergic, alpha; D044024:Tetralones; D015016:Yohimbine; C010652:BE 2254; D009638:Norepinephrine; D011224:Prazosin