Effects of prostaglandins and indomethacin on neuromuscular blocking agents.
The effects on neuromuscular blockade by d-tubocurarine and succinylcholine of inhibition of prostaglandin biosynthesis by indomethacin and of intra-arterial administration of prostoglandins E2 and F2 alpha, before and after inhibition of prostoglandin biosynthesis, were evaluated in the cat sciatic-tibialis preparation. Non-specific inhibition of prostaglandin biosynthesis by indomethacin 3 mg . kg-1 did not alter latency, maximal blockade or duration of neuromuscular blockade induced by d-tubocurarine or succinylcholine. Prostaglandin E2 antagonized twitch height depression by d-tubocurarine by an average of six per cent before and by 15% after indomethacin, but potentiated the neuromuscular block of succinylcholine by an average of five per cent before and 60% after indomethacin. Prostaglandin F2 alpha antagonized d-tubocurarine neuromuscular block by an average of 10% before and 18% after indomethacin, but potentiated succinylcholine block by an average of four per cent before and 12% after indomethacin. These results suggest that non-specific inhibition of prostaglandin biosynthesis alone does not influence d-tubocurarine or succinylcholine induced neuromuscular blockades. However, both prostaglandin E2 and F2 alpha may induce transmitter release at the neuromuscular junction that may be enhanced by indomethacin, thus antagonizing the non-depolarizing blockade of d-tubocurarine and potentiating the depolarizing blockade of succinylcholine.
D000818:Animals; D002415:Cats; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D004357:Drug Synergism; D005260:Female; D007213:Indomethacin / Q000494:pharmacology*; D008297:Male; D009469:Neuromuscular Junction / Q000187:drug effects*; D011448:Prostaglandin Antagonists / Q000494:pharmacology*; D011453:Prostaglandins / Q000096:biosynthesis; D011458:Prostaglandins E / Q000494:pharmacology*; D011460:Prostaglandins F / Q000494:pharmacology*; D013390:Succinylcholine / Q000494:pharmacology*; D014403:Tubocurarine / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D011448:Prostaglandin Antagonists; D011453:Prostaglandins; D011458:Prostaglandins E; D011460:Prostaglandins F; D013390:Succinylcholine; D014403:Tubocurarine; D007213:Indomethacin