Antinociception induced by SM 32 depends on a central cholinergic mechanism.
The antinociceptive effect of SM 32 was examined in mice by using the hot-plate (10-40 mg kg(-1) i.p; 3-30 microg per mouse i.c.v.) and abdominal constriction (10-30 mg kg(-1) i.p) tests. In the antinociceptive dose-range, SM 32 did not impair mouse spontaneous motility and motor coordination evaluated respectively by the Animex and rota-rod tests. The increase in the pain threshold produced by SM 32 was prevented by dicyclomine, pirenzepine and hemicholinium-3 but not by naloxone and CGP 35348. In vitro experiments showed that the SM 32 amplified electrically- and nicotine-evoked guinea-pig ileum contractions. On the basis of the above data, it can be postulated that SM 32 exerts its antinociceptive effect through a potentiation of central cholinergic transmission.
Ghelardini
C
C
Department of Preclinical and Clinical Pharmacology, University of Florence, Italy.
Galeotti
N
N
Gualtieri
F
F
Novella Romanelli
M
M
Bartolini
A
A
D000700:Analgesics / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D018678:Cholinergic Agents / Q000494:pharmacology*; D002799:Cholinergic Fibers / Q000187:drug effects* / Q000502:physiology; D004025:Dicyclomine / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D006168:Guinea Pigs; D006426:Hemicholinium 3 / Q000494:pharmacology; D007082:Ileum / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008124:Locomotion / Q000187:drug effects; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects*; D009943:Organophosphorus Compounds / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects; D010890:Pirenzepine / Q000494:pharmacology; D014326:Tropanes / Q000032:analysis / Q000494:pharmacology*
C106486:3-alpha-tropyl-2-(phenylthio)butyrate; D000700:Analgesics; D018678:Cholinergic Agents; D018756:GABA Antagonists; D018727:Muscarinic Antagonists; D009292:Narcotic Antagonists; D009943:Organophosphorus Compounds; D014326:Tropanes; D006426:Hemicholinium 3; D009270:Naloxone; D010890:Pirenzepine; D004025:Dicyclomine; C066430:CGP 35348