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DISTINCTION BETWEEN THE EFFECTS OF BARBITURATES, BENZODIAZEPINES AND PHENYTOIN ON RESPONSES TO γ‐AMINOBUTYRIC ACID RECEPTOR ACTIVATION AND ANTAGONISM BY BICUCULLINE AND PICROTOXIN
Author(s) -
SIMMONDS M.A.
Publication year - 1981
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.1476-5381.1981.tb16810.x
Subject(s) - muscimol , bicuculline , picrotoxin , pharmacology , chemistry , gaba receptor antagonist , gabaa receptor , long term potentiation , anticonvulsant , potency , medicine , neuroscience , receptor , biochemistry , biology , in vitro , epilepsy
1 Interactions of depressant and anticonvulsant drugs with the neuronal γ‐aminobutyric acid (GABA) receptor + effector system have been examined on afferent fibres to the rat cuneate nucleus in vitro. Three types of interaction have been measured: (a) potentiation of depolarizing responses to the GABA analogue, muscimol: (b) reduction in the potency of bicuculline as an antagonist of muscimol at the GABA receptor: (c) reduction in the potency of picrotoxin as an antagonist of muscimol acting on the effector mechanism. 2 Phenobarbitone reduced the potency of picrotoxin in doses which did not affect the potency of bicuculline and which caused only a small potentiation of muscimol. Pentobarbitone did not show such selectivity, a reduction in potency of picrotoxin always being accompanied by a reduction in potency of bicuculline and a substantial potentiation of muscimol. 3 Flurazepam and lorazepam both reduced the potency of picrotoxin without affecting that of bicuculline and with very little potentiation of muscimol. Phenytoin had no effect on the potency of picrotoxin whilst potentiating muscimol to the same extent as phenobarbitone. 4 The spectrum of drug activity in reducing the potency of picrotoxin correlates well with the reported anticonvulsant effects of these drugs against kindled amygdaloid seizures. Potentiation of muscimol and reduction of bicuculline potency appear more closely related to hypnotic properties.