1-(2-pyrimidinyl)piperazine antagonizes GABA-activated currents in cultured spinal neurones of the rat

Stephen M. Smith; David Hughes

doi:10.1016/0006-8993(89)91172-4

1-(2-pyrimidinyl)piperazine antagonizes GABA-activated currents in cultured spinal neurones of the rat

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

Abstract

Buspirone is an anxiolytic drug with an unknown mechanism of action. We have addressed the proposal that its therapeutic effect is due to a metabolite, 1-(2-pyrimidinyl)-piperazine (1-PP), increasing the open probability of γ-aminobutyric acid (GABA)-activated channels. By making whole-cell recordings from cultured spinal neurones we demonstrated that 1-PP, in contrast to flurazepam, actually antagonizes GABA- and glycine-activated currents. These observations are inconsistent with this proposed mechanism of action for buspirone.

Original language	English (US)
Pages (from-to)	366-367
Number of pages	2
Journal	Brain research
Volume	493
Issue number	2
DOIs	https://doi.org/10.1016/0006-8993(89)91172-4
State	Published - Jul 31 1989
Externally published	Yes

Keywords

1-(2-Pyrimidinyl)piperazine
Benzodiazepine
Buspirone
Chloride channel
Glycine
Neuron
Spinal cord
γ-Aminobutyric acid

ASJC Scopus subject areas

General Neuroscience
Molecular Biology
Clinical Neurology
Developmental Biology

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10.1016/0006-8993(89)91172-4

Cite this

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title = "1-(2-pyrimidinyl)piperazine antagonizes GABA-activated currents in cultured spinal neurones of the rat",

abstract = "Buspirone is an anxiolytic drug with an unknown mechanism of action. We have addressed the proposal that its therapeutic effect is due to a metabolite, 1-(2-pyrimidinyl)-piperazine (1-PP), increasing the open probability of γ-aminobutyric acid (GABA)-activated channels. By making whole-cell recordings from cultured spinal neurones we demonstrated that 1-PP, in contrast to flurazepam, actually antagonizes GABA- and glycine-activated currents. These observations are inconsistent with this proposed mechanism of action for buspirone.",

keywords = "1-(2-Pyrimidinyl)piperazine, Benzodiazepine, Buspirone, Chloride channel, Glycine, Neuron, Spinal cord, γ-Aminobutyric acid",

author = "Smith, {Stephen M.} and David Hughes",

note = "Funding Information: We thank Dr. C.A. Forbes for comments on the manuscript and Prof. J.A. Edwardson for support and encouragement. The work was supported in part by an award from the Nuffield Foundation. S.M.S. is a Foulkes Fellow.",

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T1 - 1-(2-pyrimidinyl)piperazine antagonizes GABA-activated currents in cultured spinal neurones of the rat

AU - Smith, Stephen M.

AU - Hughes, David

N1 - Funding Information: We thank Dr. C.A. Forbes for comments on the manuscript and Prof. J.A. Edwardson for support and encouragement. The work was supported in part by an award from the Nuffield Foundation. S.M.S. is a Foulkes Fellow.

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N2 - Buspirone is an anxiolytic drug with an unknown mechanism of action. We have addressed the proposal that its therapeutic effect is due to a metabolite, 1-(2-pyrimidinyl)-piperazine (1-PP), increasing the open probability of γ-aminobutyric acid (GABA)-activated channels. By making whole-cell recordings from cultured spinal neurones we demonstrated that 1-PP, in contrast to flurazepam, actually antagonizes GABA- and glycine-activated currents. These observations are inconsistent with this proposed mechanism of action for buspirone.

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KW - 1-(2-Pyrimidinyl)piperazine

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KW - Buspirone

KW - Chloride channel

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KW - Spinal cord

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1-(2-pyrimidinyl)piperazine antagonizes GABA-activated currents in cultured spinal neurones of the rat

Abstract

Keywords

ASJC Scopus subject areas

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