BMY 7378 is a selective antagonist of the D subtype of α1-adrenoceptors

Abstract BMY 7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione dihydrochloride), a 5-HT 1A receptor partial agonist, also binds to α 1 -adrenoceptors. Competition assays were performed using (±)-β-([ 125 I]iodo-4-hydroxyphenyl)-ethyl-aminomethyl-tetralone ([ 125 I]HEAT), and membranes prepared from Rat-1 fibroblasts expressing hamster α 1b -, bovine α 1c -, or rat α 1d -adrenoceptor, or their respective human homologues. Results indicate that BMY 7378 is selective for the α 1D -adrenoceptor subtype (p K i : hamster α 1b -adrenoceptor 6.2 ± 0.03, human α 1b -adrenoceptor 7.2 ± 0.05; bovine α 1c -adrenoceptor 6.1 ± 0.02, human α 1c -adrenoceptor 6.6 ± 0.20; rat α 1d -adrenoceptor 8.2 ± 0.06, human α 1d -adrenoceptor 9.4 ± 0.05) and has high affinity (pA 2 , 8.9 ± 0.1) for rat aorta α 1 -adrenoceptor.