Blockade of α2-adrenoceptors by 1-(2-pyrimidinyl)-piperazine (PmP) in vivo and its relation to the activity of buspirone

Giancarlo Bianchi, Silvio Garattini

Research output: Contribution to journalArticle

Abstract

The effect of 1-(2-pyrimidinyl)-piperazine (PmP) and the parent drug, buspirone in counteracting the behavioral and biochemical effects of clonidine were evaluated in the rat. Intraperitoneal or oral administration of PmP, buspirone and yohimbine, but not of prazosin, antagonized the slowing of gastrointestinal motility induced by subcutaneous clonidine (0.1 mg/kg). The does that inhibited the effect of clonidine on the transit time by 50% were 0.5 mg/kg i.p. and 0.7 mg/kg p.o. for PmP, 7 mg/kg i.p. and 9 mg/kg p.o. for buspirone and 0.5 mg/kg i.p. for yohimbine. PmP (0.5 mg/kg) did not block the antitransit effect of clonidine when administered by intracerebroventricular injection. The antitransit effect of a low dose of morphine (0.05 mg/kg i.p.) was not blocked by PmP (2 mg/kg i.p.). The prolongation of the hexobarbital-induced loss of the righting reflex that occurs after clonidine (0.25 mg/kg i.p.) administration was inhibited by pretreatment with PmP (0.1-2 mg/kg p.o.) or yohimbine (1 mg/kg i.p.) but not by pretreatment with prazosin (2 mg/kg i.p.). Buspirone (1-20 mg/kg) also reduced the effect of clonidine after oral administration, with a maximal effect at 5 mg/kg, whereas the same dose administered i.v. had less effect. PmP (2 mg/kg) and buspirone (15 mg/kg) raised the levels of total 3-methoxy-4-hydroxyphenylgycol (MHPG) in rat cerebral cortex, and prevented the decrease in MHPG induced by clonidine. These findings show that buspirone, in doses at which it is active as an anxiolytic, suppresses the central and peripheral effects of clonidine. This action occurs through α2-adrenoceptors and is mediated primarily by the metabolite, PmP.

Original languageEnglish
Pages (from-to)343-350
Number of pages8
JournalEuropean Journal of Pharmacology
Volume147
Issue number3
DOIs
Publication statusPublished - Mar 15 1988

Fingerprint

Buspirone
Clonidine
Adrenergic Receptors
Yohimbine
Prazosin
Oral Administration
Righting Reflex
Hexobarbital
Gastrointestinal Motility
1-(2-pyrimidinyl)piperazine
Anti-Anxiety Agents
Cerebral Cortex
Morphine
Injections

Keywords

  • 1-(2-Pyrimidinyl)-piperazine (PmP)
  • Buspirone
  • Clonidine
  • α-Adrenoceptors

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Blockade of α2-adrenoceptors by 1-(2-pyrimidinyl)-piperazine (PmP) in vivo and its relation to the activity of buspirone. / Bianchi, Giancarlo; Garattini, Silvio.

In: European Journal of Pharmacology, Vol. 147, No. 3, 15.03.1988, p. 343-350.

Research output: Contribution to journalArticle

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abstract = "The effect of 1-(2-pyrimidinyl)-piperazine (PmP) and the parent drug, buspirone in counteracting the behavioral and biochemical effects of clonidine were evaluated in the rat. Intraperitoneal or oral administration of PmP, buspirone and yohimbine, but not of prazosin, antagonized the slowing of gastrointestinal motility induced by subcutaneous clonidine (0.1 mg/kg). The does that inhibited the effect of clonidine on the transit time by 50{\%} were 0.5 mg/kg i.p. and 0.7 mg/kg p.o. for PmP, 7 mg/kg i.p. and 9 mg/kg p.o. for buspirone and 0.5 mg/kg i.p. for yohimbine. PmP (0.5 mg/kg) did not block the antitransit effect of clonidine when administered by intracerebroventricular injection. The antitransit effect of a low dose of morphine (0.05 mg/kg i.p.) was not blocked by PmP (2 mg/kg i.p.). The prolongation of the hexobarbital-induced loss of the righting reflex that occurs after clonidine (0.25 mg/kg i.p.) administration was inhibited by pretreatment with PmP (0.1-2 mg/kg p.o.) or yohimbine (1 mg/kg i.p.) but not by pretreatment with prazosin (2 mg/kg i.p.). Buspirone (1-20 mg/kg) also reduced the effect of clonidine after oral administration, with a maximal effect at 5 mg/kg, whereas the same dose administered i.v. had less effect. PmP (2 mg/kg) and buspirone (15 mg/kg) raised the levels of total 3-methoxy-4-hydroxyphenylgycol (MHPG) in rat cerebral cortex, and prevented the decrease in MHPG induced by clonidine. These findings show that buspirone, in doses at which it is active as an anxiolytic, suppresses the central and peripheral effects of clonidine. This action occurs through α2-adrenoceptors and is mediated primarily by the metabolite, PmP.",
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