Prochlorperazine induces central antinociception mediated by the muscarinic system.

The antinociceptive effect of the D2 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 D2 selective agonist quinpirole, the unselective muscarinic antagonist atropine, theM1 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 M1 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 GABAB 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.