1-(2-Pyrimidinyl)piperazine antagonizes GABA-activated currents in cultured spinal neurones of the rat.
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 gamma-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.
MRC Neurochemical Pathology Unit, Newcastle General Hospital, U.K.
S M
SM
Smith
D
D
Hughes
D000818:Animals; D002065:Buspirone / Q000031:analogs & derivatives* / Q000494:pharmacology; D002478:Cells, Cultured; D008564:Membrane Potentials / Q000187:drug effects; D051381:Rats; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D005680:gamma-Aminobutyric Acid; C037921:1-(2-pyrimidinyl)piperazine; D002065:Buspirone