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

Stephen M. Smith
, David Hughes

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

Funding

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.

Funders
Nuffield Foundation

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

Access to Document

10.1016/0006-8993(89)91172-4

Cite this

@article{1a83482305294e928db8b0e050547ad3,

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.",

year = "1989",

month = jul,

day = "31",

doi = "10.1016/0006-8993(89)91172-4",

language = "English (US)",

volume = "493",

pages = "366--367",

journal = "Brain Research",

issn = "0006-8993",

publisher = "Elsevier BV",

number = "2",

}

TY - JOUR

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.

PY - 1989/7/31

Y1 - 1989/7/31

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.

AB - 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.

KW - 1-(2-Pyrimidinyl)piperazine

KW - Benzodiazepine

KW - Buspirone

KW - Chloride channel

KW - Glycine

KW - Neuron

KW - Spinal cord

KW - γ-Aminobutyric acid

UR - https://www.scopus.com/pages/publications/0024315136

UR - https://www.scopus.com/pages/publications/0024315136#tab=citedBy

U2 - 10.1016/0006-8993(89)91172-4

DO - 10.1016/0006-8993(89)91172-4

M3 - Article

C2 - 2765902

AN - SCOPUS:0024315136

SN - 0006-8993

VL - 493

SP - 366

EP - 367

JO - Brain Research

JF - Brain Research

IS - 2

ER -

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

Abstract

Funding

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this