Prostaglandin antagonism by sodium p-benzyl-4-[1-oxo-2-(4-chlorobenzyl)-3-phenylpropyl]pheenyl phosphonate (N-0164).
1 The ability of sodium p-benzyl-4-[1-oxo-2-(4-chlorobenzyl)-3-phenylpropyl]phenyl phosphonate (N-0164) to antagonize contractions produced by prostaglandins E2 and F2a on isolated preparations of gerbil, rat and guinea-pig gastrointestinal muscle has been studied. 2 N-0164 was found to be a potent, partially selective prostaglandin antagonist in these isolated smooth muscle preparations. The blockade produced by N-0164 in the isolated stomach strip of the rat had some, but not all, the characteristics of a competitive antagonism. 3 N-0164 produced a dose-dependent decrease in tone in the rat stomach strip that was abolished by pretreatment of the preparation with indomethacin. 4 N-0164 prevented diarrhoea induced by prostaglandin E2 in mice when given by intraperitoneal injection but was less effective when given orally. 5 N-0164 inhibited oedema induced with croton-oil and pyridine-ether in the mouse ear. 6 N-0164 delayed the onset of erythema following ultraviolet irradiation of guinea-pig skin only when an equimolar amount of pralidoxime chloride was added to the vehicle. 7 It is concluded that N-0164 is a potent, partially selective prostaglandin antagonist on several isolated smooth msucle preparations. N-0164 exhibits activity in vivo particularly following local application when problems associated with penetration and distribution are minimized.
D000818:Animals; D003106:Colon / Q000187:drug effects; D003967:Diarrhea / Q000188:drug therapy; D004487:Edema / Q000188:drug therapy; D004890:Erythema / Q000188:drug therapy; D005849:Gerbillinae; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D011448:Prostaglandin Antagonists; D011458:Prostaglandins E / Q000494:pharmacology; D011460:Prostaglandins F / Q000494:pharmacology; D051381:Rats; D013270:Stomach / Q000187:drug effects
D063065:Organophosphonates; D009943:Organophosphorus Compounds; D011448:Prostaglandin Antagonists; D011458:Prostaglandins E; D011460:Prostaglandins F; C012641:N 0164