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Two distinct interactions of barbiturates and chlormethiazole with the GABA A receptor complex in rat cuneate nucleus in vitro
Author(s) -
Harrison N.L.,
Simmonds M. A.
Publication year - 1983
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.1476-5381.1983.tb10045.x
Subject(s) - muscimol , picrotoxin , bicuculline , chemistry , gabaa receptor , pharmacology , cuneate nucleus , gaba receptor antagonist , strychnine , anticonvulsant , receptor , neuroscience , nucleus , biochemistry , biology , epilepsy
1 Some pharmacological properties of the GABA A receptor complex in the rat cuneate nucleus slice have been assessed from depolarization responses to the γ‐aminobutyric acid (GABA) analogue muscimol and antagonism of the responses by bicuculline and picrotoxin. 2 Responses to muscimol were potentiated by the following drugs, in descending order of potency with regard to the concentrations required in the Krebs medium: (±)‐5‐(1,3‐dimethylbutyl)‐5‐ethylbarbituric acid ((±)‐DMBB) = (±)‐quinalbarbitone = (± pentobarbitone > (±)‐methyl‐phenobarbitone = (−)‐methylphenobarbitone > butobarbitone = chlormethiazole > phenobarbitone > barbitone = (+)‐methylphenobarbitone. Primidone and phenylethylmalonamide were inactive. Calculation of the concentrations likely to be present in membrane lipids for equal potentiations of muscimol revealed little difference between quinalbarbitone, pentobarbitone, phenobarbitone and barbitone. 3 The effect of picrotoxin as a muscimol antagonist was selectively reduced only by DMBB, chlormethiazole, phenobarbitone and (−)‐methylphenobarbitone in concentrations that caused only a modest potentiation of muscimol. 4 It is suggested that a specific site of action in the GABA A receptor complex is involved in the reduction of picrotoxin effect and that this may be relevant to the anticonvulsant properties of chlormethiazole, phenobarbitone and (−)‐methylphenobarbitone. The potentiation of muscimol by chlormethiazole and the barbiturates in general involves a distinctly different site that is less selective and this may underlie the hypnotic properties of these drugs.