The AMPA receptor antagonist GYKI 52466 reverses the anti-cataleptic effects of the competitive NMDA receptor antagonist CGP 37849.
نویسندگان
چکیده
The effects of the AMPA receptor antagonist GYKI 52466 (1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine HCl) on haloperidol-induced catalepsy were tested in drug-naive rats and in rats pretreated with the competitive NMDA receptor antagonist CGP 37849 (DL-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid). CGP 37849 (4 mg/kg i.p.) given alone significantly reversed haloperidol-induced catalepsy (0.5 mg/kg i.p.) while GYKI 52466 (4.8 mg/kg i.p.) given alone was without effect. Administration of GYKI 52466 to rats pretreated with CGP 37849 abolished the anticataleptic effects of the competitive NMDA receptor antagonist seen following single administration. Thus the AMPA receptor antagonist prevents behavioural effects induced by a NMDA receptor antagonist in this behavioural model.
منابع مشابه
GYKI 52466, a 2,3-benzodiazepine, is a highly selective, noncompetitive antagonist of AMPA/kainate receptor responses.
In whole-cell voltage-clamp recordings from cultured rat hippocampal neurons, the 2,3-benzodiazepine GYKI 52466 was a potent antagonist of kainate- and AMPA-activated currents (IC50 values, 7.5 and 11 microM, respectively), but was inactive against N-methyl-D-aspartate (NMDA) or gamma-aminobutyric acid responses. The block produced by GYKI 52466 occurred in a noncompetitive fashion, was voltage...
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The neurotransmitter glutamate plays a pivotal role in the development of the neuropathological sequelae following acute seizures. Our previous data proved the efficacy of the NMDA-receptor antagonists on the symptoms, survival and neuronal activation in the 4-aminopyridine- (4-AP) induced seizures. In this study, we examined the effects of two different doses of a non-competitive, selective, a...
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GYKI 52466 [1,4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine], a non-competitive AMPA/kainate receptor antagonist, administered i.p. at the dose of 5 mg/kg, exerted a significant anticonvulsant effect, as it decreased seizure and afterdischarge durations, being ineffective at 2 mg/kg. Subsequently, GYKI 52466 (2 mg/kg) was combined with antiepileptic drugs at doses ineffective...
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متن کاملTreatment of early and late kainic acid-induced status epilepticus with the noncompetitive AMPA receptor antagonist GYKI 52466.
PURPOSE Benzodiazepines such as diazepam may fail to effectively treat status epilepticus because benzodiazepine-sensitive GABA(A) receptors are progressively internalized with continued seizure activity. Ionotropic glutamate receptors, including AMPA receptors, are externalized, so that AMPA receptor antagonists, which are broad-spectrum anticonvulsants, could be more effective treatments for ...
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عنوان ژورنال:
- European journal of pharmacology
دوره 256 3 شماره
صفحات -
تاریخ انتشار 1994