title: BMY 7378 is a selective antagonist of the D subtype of alpha 1-adrenoceptors.
abstract: BMY 7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8- azaspiro[4.5]decane-7,9-dione dihydrochloride), a 5-HT1A receptor partial agonist, also binds to alpha 1-adrenoceptors. Competition assays were performed using (+/-)-beta-([125I]iodo-4-hydroxyphenyl)-ethyl-aminomethyl-tetralone ([125I]HEAT), and membranes prepared from Rat-1 fibroblasts expressing hamster alpha 1b-, bovine alpha 1c-, or rat alpha 1d-adrenoceptor, or their respective human homologues. Results indicate that BMY 7378 is selective for the alpha 1D-adrenoceptor subtype (pKi: hamster alpha 1b-adrenoceptor 6.2 +/- 0.03, human alpha 1b-adrenoceptor 7.2 +/- 0.05; bovine alpha 1c-adrenoceptor 6.1 +/- 0.02, human alpha 1c-adrenoceptor 6.6 +/- 0.20; rat alpha 1d-adrenoceptor 8.2 +/- 0.06, human alpha 1d-adrenoceptor 9.4 +/- 0.05) and has high affinity (pA2, 8.9 +/- 0.1) for rat aorta alpha 1-adrenoceptor.
authors.affiliation: Department of Cellular Biochemistry, Glaxo Research Institute, Research Triangle Park, NC 27709, USA.
authors.forename: A S
authors.initials: AS
authors.lastname: Goetz
authors.forename: H K
authors.initials: HK
authors.lastname: King
authors.forename: S D
authors.initials: SD
authors.lastname: Ward
authors.forename: T A
authors.initials: TA
authors.lastname: True
authors.forename: T J
authors.initials: TJ
authors.lastname: Rimele
authors.forename: D L
authors.initials: DL
authors.lastname: Saussy
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D006224:Cricetinae; D006801:Humans; D010879:Piperazines / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D018340:Receptors, Adrenergic, alpha-1 / Q000145:classification / Q000378:metabolism
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D010879:Piperazines; D018340:Receptors, Adrenergic, alpha-1; C053428:BMY 7378