Receptor binding profile of tibalosine, a new antihypertensive

The ability of 1-(2,3-dihydro-5-benzo[b]thienyl]-2-(4-phenylbutylamino)-1- propanol-(erythro) (tibalosine, CP 804 S), a new antihypertensive agent, to interact with 11 different receptors has been studied by binding assays. Tibalosine interacts specifically with alpha- and beta-adrenergic receptors and calcium channel binding sites. Ki values (nmol/l) for inhibition of specific binding are 26, 1000, 1000 and 770 respectively for the alpha 1-adrenergic, beta 1- and beta 2-adrenergic receptors and calcium channel binding sites. The interaction with adrenergic receptors is stereoselective since CP 804 S/T, the threo derivative of tibalosine, exhibits Ki values 8 to 10 times higher than those of tibalosine. The selectivity ratio between alpha 1- and alpha 2-adrenergic receptors is about 400. Tibalosine and CP 804 S/T interact with the low affinity binding sites labelled by 3H-WB 4101 in rat brain membranes. These binding sites for putative Ca2+ channel inhibitors are present in rat heart membranes and have the same characteristics as those in rat brain membranes. These results are discussed in relation with the mechanism of tibalosine antihypertensive effect.