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Anticonflict effect of ipsapirone, buspirone and gepirone is not mediated by their common metabolite 1-(2-pyrimidinyl)piperazine

E. Przegaliski

Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, 31-343 Kraków, Poland

E. Tatarczyska

Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, 31-343 Kraków, Poland

E. Chojnacka-Wójcik

Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, 31-343 Kraków, Poland

Pyrimidinylpiperazine anxiolytic drugs-ipsapirone, buspirone and gepirone-dose- dependently increased punished responding in an anticonflict (shock-induced suppression of drinking) paradigm in rats. Similar effect was also produced by their common metabolite 1- (2-pyrimidinyl)piperazine (1-PP). Anticonflict effects of ipsapirone, buspirone and gepirone, administered in maximal doses, were considerably stronger when tested 30 min than 120 min after their administration. Furthermore, anticonflict effects of these drugs, given in subthres hold or medium effective doses, were significantly potentiated by the non-selective drug metabolism inhibitor proadifen. Comparison of these results with literature pharmacokinetic data indicate that the pharmacological effect of ipsapirone, buspirone and gepirone parallels better cerebral concentrations of the parent drugs than 1-PP. Therefore anticonflict activity of the investigated drugs does not seem to be mediated by their common metabolite 1-PP.

Journal of Psychopharmacology, Vol. 3, No. 3, 180-185 (1989)
DOI: 10.1177/026988118900300309


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