Phosphinic acid analogues of GABA are antagonists at the GABAB receptor in the rat anococcygeus.
CGP 35348 (3-aminopropyl(diethoxymethyl)phosphinic acid) and 3-aminopropyl(n-hexyl)phosphinic acid (3-APHPA) were tested in the rat anococcygeus muscle against CGP 27492 (3-aminopropylphosphinic acid), a selective GABAB agonist, for their antagonist activity. Their antagonist potency was compared with that of 2-hydroxysaclofen. The pA2 values for CGP 35348, 3-APHPA and 2-hydroxysaclofen were 5.38, 4.86, 4.45 respectively in the rat anococcygeus muscle. These results confirm the previous reports of GABAB antagonist activity for these compounds and show a marginal improvement in potency over 2-hydroxysaclofen.
Hills
J M
JM
Smith Kline Beecham Pharmaceuticals Ltd., Welwyn, Herts.
Sellers
A J
AJ
Mistry
J
J
Broekman
M
M
Howson
W
W
D000818:Animals; D004558:Electric Stimulation; D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009132:Muscles / Q000187:drug effects*; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D051381:Rats; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D009943:Organophosphorus Compounds; C061388:3-aminopropylphosphinic acid; C068458:3-aminopropyl(hexyl)phosphinic acid; D005680:gamma-Aminobutyric Acid; C066430:CGP 35348