title: Acetyl-l-carnitine induces muscarinic antinocieption in mice and rats.
abstract: The analgesic activity of acetyl-L-carnitine (ALCAR) in neuropathic pain is well established. By contrast, its potential efficacy in the relief of acute pain has not been reported. The antinociceptive effect of ALCAR was, therefore, examined in the mouse hot-plate and abdominal constriction tests, and in the rat paw-pressure test. ALCAR (100 mg kg(-1) s.c. twice daily for seven days) produced an increase of the pain threshold in both mice and rats. ALCAR was also able to reverse hyperalgesia induced by kainic acid and NMDA administration in the mouse hot-plate test. The antinociception produced by ALCAR was prevented by the unselective muscarinic antagonist atropine, the M(1) selective antagonists pirenzepine and S-(-)-ET126, and by the choline uptake inhibitor hemicholinium-3 (HC-3). By contrast the analgesic effect of ALCAR was not prevented by the opioid antagonist naloxone, the GABA(B) antagonist CGP 35348, the monoamine synthesis inhibitor (alpha)-methyl-p-tyrosine, and the Gi-protein inactivator pertussis toxin. Moreover, ALCAR antinociception was abolished by pretreament with an antisense oligonucleotide (aODN) against the M(1) receptor subtype, administered at the dose of 2 nmol per single i.c.v injection. On the basis of the above data, it can be postulated that ALCAR exerted an antinociceptive effect mediated by a central indirect cholinergic mechanism. In the antinociceptive dose-range, ALCAR did not impair mouse performance evaluated by the rota-rod and hole-board tests.
authors.affiliation: Department of Preclinical and Clinical Pharmacology, University of Florence, Viale G Pieraccini 6, I-50139, Florence, Italy. carla.gherlardini@unifi.it
authors.forename: Carla
authors.initials: C
authors.lastname: Ghelardini
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Galeotti
authors.forename: Menotti
authors.initials: M
authors.lastname: Calvani
authors.forename: Luigi
authors.initials: L
authors.lastname: Mosconi
authors.forename: Raffaella
authors.initials: R
authors.lastname: Nicolai
authors.forename: Alessandro
authors.initials: A
authors.lastname: Bartolini
mesh_terms: D000108:Acetylcarnitine / Q000494:pharmacology*; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D051379:Mice; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000502:physiology*
chemical_list: D000700:Analgesics; D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D000108:Acetylcarnitine