TY - JOUR
T1 - Zomepirac
T2 - preclinical narcotic abuse liability evaluation
AU - Woods, J. H.
AU - Young, A. M.
AU - Medzihradsky, F.
AU - Smith, C. B.
AU - Aceto, M. D.
AU - Harris, L. S.
AU - Jacobson, A. E.
N1 - Copyright:
Copyright 2012 Elsevier B.V., All rights reserved.
PY - 1983
Y1 - 1983
N2 - 5-(4-Chlorobenzoyl)-1,4-dimethyl-1H-pyrrole-2-acetate dihydrate (Zomepirac, Zomax®) was assessed in a variety of preparations in which narcotic agonists and antagonists have distinctive profiles. Zomepirac failed to displace tritiated etorphine significantly at concentrations up to 200 μmol/l. It was active (3-7 x 10 -5 mol/l) on both the electrically stimulated guinea pig ileum and mouse vas deferens but was less efficacious than morphine; these effects were not reversed by narcotic antagonists. Zomepirac was inactive in some analgesic assays in mice; tail-flick (1-30 mg/kg s.c.); hot plate (1-100 mg/kg s.c.); Nilsen (1-50 mg/kg s.c.); it was also inactive (1-10 mg/kg s.c.) as an antagonist of morphine in the tail-flick assay. It was, however, active in the paraphenylquinone writhing assay; this action was not reversed by naloxone (1-10 mg/kg). Zomepirac (2.5-10 mg/kg s.c.) failed to suppress signs of withdrawal produced by morphine deprivation in dependent rhesus monkeys. The intraperitoneal infusion of high doses of zomepirac (50 mg/kg 24 h or more) in rats produced toxicity. However, lower doses failed to induce narcotic-like dependence over a 6-7-day infusion period. The compound failed to maintain intravenous drug self-administration responding in rhesus monkeys over a range of doses (0.1-3.2 mg/kg) although codeine did so. In rhesus monkeys trained to discriminate narcotic agonists (etorphine or ethylketazocine) from saline, zomepirac (1-10 mg/kg i.m.) failed to produce drug-appropriate responding. Thus, zomepirac appears to possess few, if any, of the characteristic actions of narcotics that are associated with their abuse liability.
AB - 5-(4-Chlorobenzoyl)-1,4-dimethyl-1H-pyrrole-2-acetate dihydrate (Zomepirac, Zomax®) was assessed in a variety of preparations in which narcotic agonists and antagonists have distinctive profiles. Zomepirac failed to displace tritiated etorphine significantly at concentrations up to 200 μmol/l. It was active (3-7 x 10 -5 mol/l) on both the electrically stimulated guinea pig ileum and mouse vas deferens but was less efficacious than morphine; these effects were not reversed by narcotic antagonists. Zomepirac was inactive in some analgesic assays in mice; tail-flick (1-30 mg/kg s.c.); hot plate (1-100 mg/kg s.c.); Nilsen (1-50 mg/kg s.c.); it was also inactive (1-10 mg/kg s.c.) as an antagonist of morphine in the tail-flick assay. It was, however, active in the paraphenylquinone writhing assay; this action was not reversed by naloxone (1-10 mg/kg). Zomepirac (2.5-10 mg/kg s.c.) failed to suppress signs of withdrawal produced by morphine deprivation in dependent rhesus monkeys. The intraperitoneal infusion of high doses of zomepirac (50 mg/kg 24 h or more) in rats produced toxicity. However, lower doses failed to induce narcotic-like dependence over a 6-7-day infusion period. The compound failed to maintain intravenous drug self-administration responding in rhesus monkeys over a range of doses (0.1-3.2 mg/kg) although codeine did so. In rhesus monkeys trained to discriminate narcotic agonists (etorphine or ethylketazocine) from saline, zomepirac (1-10 mg/kg i.m.) failed to produce drug-appropriate responding. Thus, zomepirac appears to possess few, if any, of the characteristic actions of narcotics that are associated with their abuse liability.
UR - http://www.scopus.com/inward/record.url?scp=0020662559&partnerID=8YFLogxK
M3 - Article
C2 - 6133523
AN - SCOPUS:0020662559
VL - 33
SP - 218
EP - 222
JO - Arzneimittel-Forschung/Drug Research
JF - Arzneimittel-Forschung/Drug Research
SN - 0004-4172
IS - 2
ER -