Analgesic activities of PEM-420, the active eutomer of pemedolac.
PEM-420, the active isomer of pemedolac, inhibited the writhing responses induced by phenylbenzoquinone (PBQ), acetic acid, and acetylcholine in mice with ED50's of 0.80, 0.92, and 0.075 mg/kg p.o., respectively. In the rat acetic acid writhing assay, PEM-420 exhibited an ED50 value of 8.4 mg/kg p.o. In the Randall-Selitto test, PEM-420 raised the pain threshold of the yeast-injected paw (ED50 = 0.55 mg/kg p.o.). Like other NSAIDs, PEM-420 inhibited the PBQ-induced production of PGI2 and PGE2 in the mouse peritoneal cavity, with ED50 values of 0.5 and 1.2 mg/kg p.o., respectively. It had weak ulcerogenic liability in rats (acute UD50 = 99 mg/kg p.o. in fasted rats; subacute UD50 = 74 mg/kg/day for 4 days in fed rats). The data indicate that PEM-420 is a potent and safe peripheral analgesic.
Chau
T
T
Wyeth-Ayerst Research, Princeton, NJ 08543-8000.
Walter
T
T
Zimmerman
J
J
Hartman
D
D
Ochalski
S
S
Weichman
B
B
D000085:Acetates; D019342:Acetic Acid; D000109:Acetylcholine; D000284:Administration, Oral; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D016227:Benzoquinones; D015232:Dinoprostone / Q000096:biosynthesis; D011464:Epoprostenol / Q000096:biosynthesis; D007210:Indoleacetic Acids / Q000494:pharmacology* / Q000633:toxicity; D007279:Injections, Subcutaneous; D051379:Mice; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects*; D051381:Rats; D013237:Stereoisomerism
D000085:Acetates; D000700:Analgesics; D016227:Benzoquinones; D007210:Indoleacetic Acids; C029322:phenylbenzoquinone; D011464:Epoprostenol; D015232:Dinoprostone; D000109:Acetylcholine; C056040:pemedolac; D019342:Acetic Acid