Modulation of benzodiazepine receptor binding: Insight into pharmacological efficacy

Frederick J. Ehlert; Paul Ragan; Andrew Chen; William R. Roeske; Henry I. Yamamura

doi:10.1016/0014-2999(82)90246-1

Modulation of benzodiazepine receptor binding: Insight into pharmacological efficacy

Frederick J. Ehlert
, Paul Ragan
, Andrew Chen
, William R. Roeske
, Henry I. Yamamura

Research output: Contribution to journal › Article › peer-review

51 Scopus citations

Abstract

The effects of GABA on the binding of analogues of benzodiazepine, triazolopyridazines, β-carbolines and imidazodiazepines were examined in ligand/[³H]flunitrazepan competition experiments. GABA increased the potency of anxiolytics, like flunitrazepam, whereas the potency of benzodiazepine antagonists, like Ro15-1788, was largely insensitive to the influence of GABA. Several other agents including pyrazolopyridines, barbiturates and etomidate caused a chloride dependent enhancement of [³H]flunitrazepam binding but not an enhancement of [³H]propyl-β-carboline-3-carboxylate binding.

Original language	English (US)
Pages (from-to)	249-253
Number of pages	5
Journal	European Journal of Pharmacology
Volume	78
Issue number	2
DOIs	https://doi.org/10.1016/0014-2999(82)90246-1
State	Published - Feb 26 1982

Keywords

Barbiturates
Benzodiazepine receptor agonists and antagonists
Etomidate
GABA
Pyrazolopyridines

ASJC Scopus subject areas

Pharmacology

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10.1016/0014-2999(82)90246-1

Cite this

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title = "Modulation of benzodiazepine receptor binding: Insight into pharmacological efficacy",

abstract = "The effects of GABA on the binding of analogues of benzodiazepine, triazolopyridazines, β-carbolines and imidazodiazepines were examined in ligand/[3H]flunitrazepan competition experiments. GABA increased the potency of anxiolytics, like flunitrazepam, whereas the potency of benzodiazepine antagonists, like Ro15-1788, was largely insensitive to the influence of GABA. Several other agents including pyrazolopyridines, barbiturates and etomidate caused a chloride dependent enhancement of [3H]flunitrazepam binding but not an enhancement of [3H]propyl-β-carboline-3-carboxylate binding.",

keywords = "Barbiturates, Benzodiazepine receptor agonists and antagonists, Etomidate, GABA, Pyrazolopyridines",

author = "Ehlert, \{Frederick J.\} and Paul Ragan and Andrew Chen and Roeske, \{William R.\} and Yamamura, \{Henry I.\}",

note = "Funding Information: The authors thank Dr. William Haefely of Hoffman-LaRoehc, Basle, Switzerland, for providing the Ro-15-1788, Dr. Josee Leysen of Janssen Pharmaceuticals for providing the enantiomers of e\textbackslash{}[omidatc and Dr. Jeffrey Malick of ICI Pharmaceuticals for providing tracazolate. We also thank Susan Yamamura for computer programming assistance. Part of this work was supported by Public Health Service Grants MH-27257, MH-30626, HL-21486 and Program Project Grant HL-20984 and the Arizona Committee to Combat Huntington's Disease.H .I.Y. is a recipient of a USPHS Research Scientist Development Award, Type II (MH-00095), from the National Institute of mental Health, and W.I\textasciitilde{}.R. is a recipient of a usPHS R.esearch Career Development Award (HL-00776) from the National Heart Lung and Blood Institute.",

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doi = "10.1016/0014-2999(82)90246-1",

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AU - Yamamura, Henry I.

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PY - 1982/2/26

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N2 - The effects of GABA on the binding of analogues of benzodiazepine, triazolopyridazines, β-carbolines and imidazodiazepines were examined in ligand/[3H]flunitrazepan competition experiments. GABA increased the potency of anxiolytics, like flunitrazepam, whereas the potency of benzodiazepine antagonists, like Ro15-1788, was largely insensitive to the influence of GABA. Several other agents including pyrazolopyridines, barbiturates and etomidate caused a chloride dependent enhancement of [3H]flunitrazepam binding but not an enhancement of [3H]propyl-β-carboline-3-carboxylate binding.

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Modulation of benzodiazepine receptor binding: Insight into pharmacological efficacy

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