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

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

Research output: Contribution to journalArticle

22 Citations (Scopus)

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

Fingerprint

Corticosterone
1-(2-pyrimidinyl)piperazine
gepirone
Pharmaceutical Preparations

Keywords

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

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Drug Discovery
  • Pharmacology

Cite this

The effects of gepirone and 1-(2-pyrimidinyl)-piperazine on levels of corticosterone in rat plasma. / Matheson, G. K.; Gage-White, Deanna; White, Gary; Guthrie, Deanne; Rhoades, Janet; Dixon, Vanessa.

In: Neuropharmacology, Vol. 28, No. 4, 1989, p. 329-334.

Research output: Contribution to journalArticle

Matheson, G. K. ; Gage-White, Deanna ; White, Gary ; Guthrie, Deanne ; Rhoades, Janet ; Dixon, Vanessa. / The effects of gepirone and 1-(2-pyrimidinyl)-piperazine on levels of corticosterone in rat plasma. In: Neuropharmacology. 1989 ; Vol. 28, No. 4. pp. 329-334.
@article{4b2b6b15f5fa4382a1de2592a49564a4,
title = "The effects of gepirone and 1-(2-pyrimidinyl)-piperazine on levels of corticosterone in rat plasma",
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.",
keywords = "1-(2-pyrimidinyl)-piperazine, anxiolytics, BMY-13805, corticosterone, gepirone, serotonin, stress",
author = "Matheson, {G. K.} and Deanna Gage-White and Gary White and Deanne Guthrie and Janet Rhoades and Vanessa Dixon",
year = "1989",
doi = "10.1016/0028-3908(89)90026-9",
language = "English",
volume = "28",
pages = "329--334",
journal = "Neuropharmacology",
issn = "0028-3908",
publisher = "Elsevier Limited",
number = "4",

}

TY - JOUR

T1 - The effects of gepirone and 1-(2-pyrimidinyl)-piperazine on levels of corticosterone in rat plasma

AU - Matheson, G. K.

AU - Gage-White, Deanna

AU - White, Gary

AU - Guthrie, Deanne

AU - Rhoades, Janet

AU - Dixon, Vanessa

PY - 1989

Y1 - 1989

N2 - 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.

AB - 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.

KW - 1-(2-pyrimidinyl)-piperazine

KW - anxiolytics

KW - BMY-13805

KW - corticosterone

KW - gepirone

KW - serotonin

KW - stress

UR - http://www.scopus.com/inward/record.url?scp=0024513343&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0024513343&partnerID=8YFLogxK

U2 - 10.1016/0028-3908(89)90026-9

DO - 10.1016/0028-3908(89)90026-9

M3 - Article

C2 - 2747846

AN - SCOPUS:0024513343

VL - 28

SP - 329

EP - 334

JO - Neuropharmacology

JF - Neuropharmacology

SN - 0028-3908

IS - 4

ER -