Prochlorperazine induces central antinociception mediated by the muscarinic system

  • Ghelardini C
  • Galeotti N
  • Uslenghi C
 et al. 
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Abstract

The antinociceptive effect of the D2antagonist prochlorperazine was examined in the mouse hot-plate and abdominal constriction tests. Prochlorperazine (1-2 mg kg-1s.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 D2selective agonist quinpirole, the unselective muscarinic antagonist atropine, the M1selective 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 M1receptor 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 GABABantagonist 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. © 2004 Elsevier Ltd. All rights reserved.

Author-supplied keywords

  • Acetylcholine
  • HC-3
  • M1muscarinic receptor subtype
  • Prochlorperazine
  • aODN
  • antisense oligodeoxynucleotide
  • dODN
  • degenerate oligodeoxynucleotide
  • hemicolinium-3 hydrobromide
  • i.c.v.
  • i.p.
  • intracerebroventricular
  • intraperitoneal
  • s.c.
  • subcutaneous

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Authors

  • Nicoletta GaleottiUniversity of Florence Department of Neurosciences, Psychology, Drug Area and Child Health

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  • Carla Ghelardini

  • Carla Uslenghi

  • Irene Grazioli

  • Alessandro Bartolini

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