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Ketamine‐inhibition of calcium‐induced contractions in depolarized rat uterus: a comparison with other calcium antagonists
Author(s) -
Calixto João B.,
Loch Sirley
Publication year - 1985
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1985.tb08846.x
Subject(s) - papaverine , verapamil , ketamine , chemistry , theophylline , calcium , pharmacology , contraction (grammar) , endocrinology , anesthesia , medicine , organic chemistry
1 The inhibitory effect of the intravenous anaesthetic ketamine on CaCl 2 ‐induced contractions in the isolated K + ‐depolarized uterus of the rat in Ca 2+ ‐free medium was compared with that produced by papaverine, theophylline and the calcium entry blocker verapamil. 2 Pre‐incubation for 20 min with either ketamine (0.3 to 3 mM), papaverine (3 to 30 μM), theophylline (0.1 to 1 mM) or verapamil (3 to 30 nM) induced parallel, concentration‐dependent rightward displacements of the dose‐response curves to Ca 2+ (0.04 to 22 mM). The antagonism was competitive, except that due to verapamil, the Schild plot for which yielded a slope which differed significantly from unity. The calculated pA 2 values (± s.e.mean) were: ketamine 3.90 ± 0.07; papaverine 5.55 ± 0.05; theophylline 3.99 ± 0.1 and verapamil 9.54 ± 0.24 3 These drugs differed in their ability to relax the sustained contraction induced by Ca 2+ (1 mM) in K + ‐depolarizing solution. Ketamine and verapamil relaxed the preparation in a concentration‐dependent manner whereas theophylline and especially papaverine were less potent and induced only partial maximal relaxation. The t 1/2 of the relaxant effect was significantly less for ketamine than for verapamil (5 and 22 min, respectively). Only ketamine produced a relaxation comparable to that obtained by washing the preparation with Ca 2+ ‐free solution ( t 1/2 = approx. 5 min). 4 Prior exposure of the depolarized uterine strip to a low concentration of Ca 2+ (0.22 mM) increased the potency of ketamine, but decreased that of papaverine and theophylline, in antagonizing Ca 2+ ‐induced contractions. In contrast, this procedure did not affect the potency of verapamil. 5 The inhibitory effects of these drugs, excluding those of verapamil, were completely reversed after washing the preparations with a high‐potassium Ca 2+ ‐free solution, 3–5 times for about 30–60 min. 6 These experiments provide further evidence that the relaxant effect produced by ketamine on the rat isolated uterus is due to its ability to antagonize Ca 2+ movements competitively and also show that there are marked differences between the nature of the relaxant effects of ketamine and those of papaverine, theophylline and verapamil.