Prochlorperazine induces central antinociception mediated by the muscarinic system.

Abstract:

:The antinociceptive effect of the D(2) antagonist prochlorperazine was examined in the mouse hot-plate and abdominal constriction tests. Prochlorperazine (1-2 mg kg(-1) s.c./i.p.) produced an increase of the pain threshold in the mouse hot-plate test. The antinociception produced by prochlorperazine was prevented by the D(2) selective agonist quinpirole, the unselective muscarinic antagonist atropine, the M(1) selective antagonist pirenzepine, and by the choline uptake inhibitor hemicholinium-3 hydrobromide (HC-3). Moreover, prochlorperazine antinociception was abolished by pretreatment with an aODN against the M(1) receptor subtype, administered at the dose of 2 nmol per single i.c.v. injection. By contrast the analgesic effect of prochlorperazine was not prevented by the opioid antagonist naloxone and the GABA(B) antagonist CGP-35348. Prochlorperazine also elicited a dose-dependent increase in ACh release from rat cerebral cortex. In the antinociceptive dose-range, prochlorperazine did not impair mouse performance evaluated by the rota-rod and hole-board tests. On the basis of the above data, it can be postulated that prochlorperazine exerted an antinociceptive effect mediated by a central cholinergic mechanism.

journal_name

Pharmacol Res

journal_title

Pharmacological research

authors

Ghelardini C,Galeotti N,Uslenghi C,Grazioli I,Bartolini A

doi

10.1016/j.phrs.2004.02.005

keywords:

subject

Has Abstract

pub_date

2004-09-01 00:00:00

pages

351-8

issue

3

eissn

1043-6618

issn

1096-1186

pii

S1043661804000507

journal_volume

50

pub_type

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