A comparison of the relative activities of a number of GABAB antagonists in the isolated vas deferens of the rat.
1. A series of GABAB receptor antagonists were tested against (+/-)-baclofen for activity on the presynaptic GABAB receptor in the rat vas deferens. 2. All the antagonists tested caused a rightward shift in the concentration-response curve to (+/-)-baclofen. 3. pA2 values calculated from full Schild analysis were as follows: phaclofen, pA2 = 4.3; delta-amino valeric acid, pA2 = 4.4; 3-aminopropyl(diethoxymethyl)phosphinic acid (CGP 35348), pA2 = 5.0; 3-amino-propyl(n-hexyl)phosphinic acid (3-APHPA), pA2 = 4.5. 4. These results show that none of the above compounds possess potent antagonist activity at the GABAB receptor (i.e. pA2 > 6) in this peripheral tissue. In addition, the more recently available phosphinic acid antagonists, appear to offer no great advance over the GABAB antagonists previously available.
SmithKline Beecham Pharmaceuticals Ltd., Welwyn, Herts.
J M
JM
Hills
M M
MM
Larkin
W
W
Howson
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D058788:GABA-B Receptor Antagonists; D066298:In Vitro Techniques; D008297:Male; D009943:Organophosphorus Compounds / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014649:Vas Deferens / Q000187:drug effects* / Q000502:physiology
D058788:GABA-B Receptor Antagonists; D009943:Organophosphorus Compounds; C068458:3-aminopropyl(hexyl)phosphinic acid; C066430:CGP 35348; D001418:Baclofen