The effects of gepirone and 1-(2-pyrimidinyl)-piperazine on levels of corticosterone in rat plasma

G. K. Matheson, Deanna Gage-White, G. White, Deanne Guthrie, Janet Rhoades, Vanessa Dixon

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

It was found that gepirone and 1-(2-pyrimidinyl)-piperazine (1-PP) increased levels of corticosterone in plasma in the intact rat. Gepirone was more potent and more efficacious than its metabolite, 1-PP. The ED50 was 6.4 μmol/kg for gepirone and 65.4 μmol/kg for 1-PP. Forty-five min after intraperitoneal administration, gepirone and 1-PP produced maximum increases in corticosterone of 283% and 211 %, respectively, above control values. The amplitude and duration of the effects of the drugs were dependent on the ongoing activity in the hypothalamic-pituitary-adrenal axis. Consequently, the greatest absolute increases in corticosterone were produced during the afternoon when the activity in the hypothalamic-pituitary-adrenal axis was greatest. A single 10 mg/kg dose of gepirone significantly elevated levels of corticosterone in plasma (313 % after 1 hr) above control values for 2 hr during afternoon trials and for 1 hr (244%) during morning trials. In addition, it was found that the effects of the administration of gepirone and of stress on the levels of corticosterone in plasma were additive. In the light of other work on the hypothalamic-pituitary-adrenal axis, these results suggest that the increased levels of corticosterone, elicited by gepirone, were mediated through a serotonergic action rather than through noradrenergic activity.

Original languageEnglish (US)
Pages (from-to)329-334
Number of pages6
JournalNeuropharmacology
Volume28
Issue number4
DOIs
StatePublished - Apr 1989

Keywords

  • 1-(2-pyrimidinyl)-piperazine
  • anxiolytics
  • BMY-13805
  • corticosterone
  • gepirone
  • serotonin
  • stress

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Drug Discovery
  • Pharmacology

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