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Analgesic profile of the sodium salt of pemedolac
Author(s) -
Chau Thuy T.,
Walter Thomas,
Katz Alan,
Weichman Barry M.
Publication year - 1993
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430280407
Subject(s) - analgesic , chemistry , (+) naloxone , potency , pharmacology , sodium , opiate , mechanism of action , antagonist , medicine , biochemistry , receptor , in vitro , organic chemistry
Pemedolac Na, 1‐ethyl‐1,3,4,9‐tetrahydro‐4‐(phenylmethyl)‐pyrano [3,4‐b] indole‐1‐acetic acid sodium salt, exhibited equipotent analgesic effects after oral, iv, and im administration, suggesting that it is well absorbed. In mouse writhing models, the ED 50 values ranged from 0.3 mg (0.81 μmol)/kg (vs. acetylcholine) to 4.3 mg (11.6 μmol)/kg (vs. paraphenylbenzoquinone [PBQ]). In the rat Randall‐Selitto model, the ED 50 o the compound was approximately 0.001 mg (2.7 nmol)/kg, with a flat dose response curve. The peak effects lasted for 7–9 h, 10–18 h, and 5 h following oral, im, and iv injections, respectively. Intracerebroventricular (i.c.v.) injections of pemedolac Na inhibited the PBQ‐induced writing in mice with an ED 50 of 43.5 μg (0.12 μmol)/mouse, and this effect was not antagonized by naloxone. It was inactive in the hot plate and tail flick tests, demonstrating that pemedolac Na does not act via an opiate mechanism. These results indicate that pemedolac Na is a viable parenteral and oral analgesic, typified by high analgesic potency, a rapid onset and long duration of action, and an extremely wide safety index. © Wiley‐Liss, Inc.