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Antinociceptive profile of the natural cholinesterase inhibitor huperzine A
Author(s) -
Galeotti Nicoletta,
Ghelardini Carla,
Di Cesare Mannelli Lorenzo,
Bartolini Alessandro
Publication year - 2001
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.1200
Subject(s) - huperzine a , mecamylamine , chemistry , pharmacology , (+) naloxone , muscarinic acetylcholine receptor , nociception , cholinesterase , analgesic , physostigmine , acetylcholine , antagonist , receptor , biochemistry , acetylcholinesterase , medicine , enzyme
Abstract The antinociceptive effect of huperzine A, a novel cholinesterase inhibitor, was investigated in the mouse hot‐plate and abdominal constriction tests. Huperzine A induced a dose‐dependent antinociception (70–110 μg kg –1 i.p.) which was prevented by scopolamine (0.1 mg kg –1 i.p.) and S‐(–)‐ET 126 (0.01 μg per mouse i.c.v.), but not by naloxone (1 mg kg –1 i.p.), mecamylamine (2 mg kg –1 i.p.), α‐methyl‐ p ‐tyrosine (100 mg kg –1 i.p.), or CGP 35348 (100 mg kg –1 i.p.). A dose‐dependent inhibition of the antinociception induced by huperzine A (110 μg kg –1 i.p.) was observed after inactivation of the M 1 gene by an antisense oligodeoxyribonucleotide (aODN). This effect was detected 24 h after the last intracerebroventricular injection of aODN. Time‐course experiments revealed that, after the end of the aODN treatment, sensitivity to analgesic drugs progressively appeared, reaching the normal range at 96 h. Huperzine A, at the maximal effective doses, did not produce any alteration of mice motor coordination, as revealed by rota‐rod experiments. These results indicate that huperzine A is endowed by muscarinic antinociceptive properties mediated by the activation of central M 1 muscarinic receptor subtype. Drug Dev. Res. 54:19–26, 2001. © 2001 Wiley‐Liss, Inc.