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Possible involvement of NMDA receptor‐mediated transmission in barbiturate physical dependence
Author(s) -
Rabbani M.,
Wright J.,
Butterworth A.R.,
Zhou Q.,
Little H.J.
Publication year - 1994
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.1476-5381.1994.tb14028.x
Subject(s) - nmda receptor , bicuculline , dizocilpine , barbiturate , barbital , gabaa receptor , antagonist , convulsion , pharmacology , kindling , chemistry , receptor , anesthesia , medicine , epilepsy , neuroscience , stimulation , psychology , biochemistry
1 The competitive antagonists at the N‐methyl‐ d ‐aspartate (NMDA) receptor, CGP39551 and CGP37849, protected against the barbiturate withdrawal syndrome in mice, as measured by ratings of convulsive behaviour on handling. 2 The effective doses of these compounds were lower than those required to prevent seizures due to NMDA in naive animals; these were in turn lower than those needed to prevent the convulsive effects of the α‐aminobutyric acid (GABA) antagonist, bicuculline. 3 The NMDA‐receptor antagonists did not alter the increase in the incidence of convulsions due to the GABA A antagonist, bicuculline, that is seen during barbiturate withdrawal, although the latencies to these convulsions during barbital withdrawal were significantly increased after CGP39551. 4 Barbiturate withdrawal did not affect the convulsive actions of NMDA, whether measured by the incidence of convulsions or by intravenous infusion. 5 The B max for [ 3 H]‐dizocilpine ([ 3 H]‐MK801) binding was significantly increased by chronic barbital treatment in cerebrocortical but not in hippocampal tissues, while the K d remained unaltered in either case. 6 At 1 h and 24 h after administration of a single dose of barbitone, the B max for [ 3 H]‐dizocilpine binding was unaltered in cerebrocortical tissue. Acute addition of barbitone in vitro did not alter [ 3 H]‐dizocilpine binding or the displacement of binding of thienylcyclohexylpyridine.