Convulsant/depressant site of action at the allosteric benzodiazepine-gaba receptor-ionophore complex

Maharaj K. Ticku; Gabor Maksay

doi:10.1016/0024-3205(83)90630-6

Convulsant/depressant site of action at the allosteric benzodiazepine-gaba receptor-ionophore complex

Maharaj K. Ticku, Gabor Maksay

Department of Pharmacology

Research output: Contribution to journal › Review article › peer-review

132 Scopus citations

Abstract

Several classes of centrally acting convulsant, depressant, anticonvulsant and anxiolytic drugs modulate GABAergic transmission. The post-synaptic receptor with which these drugs interact in an allosteric complex with distinct binding sites for GABA, benzodiazepines, picrotoxinin and related compounds. Convulsants which inhibit GABA transmission (except bicuculline) inhibit competitively the binding of dihydropicrotoxinin (DHP) or t-butylbicyclophosphorothionate (TBPT) to the picrotoxinin site and prevent the allosteric enhancing effect of depressant drugs on GABA and benzodiazepine binding. Depressant drugs give a mixed inhibition of TBPT binding. The possible topography of the picrotoxinin site and its relationship to convulsant/depressant drug action at the benzodiazepine-GABA receptor-ionophore complex is discussed.

Original language	English (US)
Pages (from-to)	2363-2375
Number of pages	13
Journal	Life Sciences
Volume	33
Issue number	24
DOIs	https://doi.org/10.1016/0024-3205(83)90630-6
State	Published - Dec 12 1983

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)
Pharmacology, Toxicology and Pharmaceutics(all)

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10.1016/0024-3205(83)90630-6

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title = "Convulsant/depressant site of action at the allosteric benzodiazepine-gaba receptor-ionophore complex",

abstract = "Several classes of centrally acting convulsant, depressant, anticonvulsant and anxiolytic drugs modulate GABAergic transmission. The post-synaptic receptor with which these drugs interact in an allosteric complex with distinct binding sites for GABA, benzodiazepines, picrotoxinin and related compounds. Convulsants which inhibit GABA transmission (except bicuculline) inhibit competitively the binding of dihydropicrotoxinin (DHP) or t-butylbicyclophosphorothionate (TBPT) to the picrotoxinin site and prevent the allosteric enhancing effect of depressant drugs on GABA and benzodiazepine binding. Depressant drugs give a mixed inhibition of TBPT binding. The possible topography of the picrotoxinin site and its relationship to convulsant/depressant drug action at the benzodiazepine-GABA receptor-ionophore complex is discussed.",

author = "Ticku, {Maharaj K.} and Gabor Maksay",

note = "Funding Information: Acknowledcjements We thank Dr. R. Ramanjaneyulu and Ms. R. Thyagarajan for assistance with this work and Mrs. M. Wilson for excellent secretarial assistance. This work was supported, in part, by grants from the National Institutes of Health (NS-15339) and National Institute of Alcohol Abuse and Alcoholism (AA 04090).",

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doi = "10.1016/0024-3205(83)90630-6",

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AU - Ticku, Maharaj K.

AU - Maksay, Gabor

N1 - Funding Information: Acknowledcjements We thank Dr. R. Ramanjaneyulu and Ms. R. Thyagarajan for assistance with this work and Mrs. M. Wilson for excellent secretarial assistance. This work was supported, in part, by grants from the National Institutes of Health (NS-15339) and National Institute of Alcohol Abuse and Alcoholism (AA 04090).

PY - 1983/12/12

Y1 - 1983/12/12

N2 - Several classes of centrally acting convulsant, depressant, anticonvulsant and anxiolytic drugs modulate GABAergic transmission. The post-synaptic receptor with which these drugs interact in an allosteric complex with distinct binding sites for GABA, benzodiazepines, picrotoxinin and related compounds. Convulsants which inhibit GABA transmission (except bicuculline) inhibit competitively the binding of dihydropicrotoxinin (DHP) or t-butylbicyclophosphorothionate (TBPT) to the picrotoxinin site and prevent the allosteric enhancing effect of depressant drugs on GABA and benzodiazepine binding. Depressant drugs give a mixed inhibition of TBPT binding. The possible topography of the picrotoxinin site and its relationship to convulsant/depressant drug action at the benzodiazepine-GABA receptor-ionophore complex is discussed.

AB - Several classes of centrally acting convulsant, depressant, anticonvulsant and anxiolytic drugs modulate GABAergic transmission. The post-synaptic receptor with which these drugs interact in an allosteric complex with distinct binding sites for GABA, benzodiazepines, picrotoxinin and related compounds. Convulsants which inhibit GABA transmission (except bicuculline) inhibit competitively the binding of dihydropicrotoxinin (DHP) or t-butylbicyclophosphorothionate (TBPT) to the picrotoxinin site and prevent the allosteric enhancing effect of depressant drugs on GABA and benzodiazepine binding. Depressant drugs give a mixed inhibition of TBPT binding. The possible topography of the picrotoxinin site and its relationship to convulsant/depressant drug action at the benzodiazepine-GABA receptor-ionophore complex is discussed.

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Convulsant/depressant site of action at the allosteric benzodiazepine-gaba receptor-ionophore complex

Abstract

ASJC Scopus subject areas

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