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Central muscarinic antinociception induced by ET‐142 and SS‐20 in rodents
Author(s) -
Ghelardini Carla,
Galeotti Nicoletta,
Fantetti Lia,
Gualtieri Fulvio,
Dei Silvia,
Scapecchi Serena,
Bartolini Alessandro
Publication year - 1997
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/(sici)1098-2299(199709)42:1<26::aid-ddr2>3.0.co;2-t
Subject(s) - nociception , pirenzepine , chemistry , muscarinic acetylcholine receptor , atropine , (+) naloxone , pharmacology , long term potentiation , cholinergic , morphine , endocrinology , medicine , opioid , receptor , biochemistry
The antinociceptive effects of ET‐142 (10–50 mg kg –1 sc; 10–30 μg per mouse icv) and SS‐20 (10–50 mg kg –1 sc; 5–30 μg per mouse icv) were examined in mice by using the hot‐plate and abdominal constriction tests. A similar antinociceptive profile for both compounds (20–40 mg kg –1 ip) was also observed in rats using the paw pressure test. In the antinociceptive dose‐range, ET‐142 and SS‐20 did not impair mouse gross behavior and motor coordination evaluated, respectively, by the Irwin and rotarod tests. The increase in the pain threshold produced by ET‐142 and SS‐20 was prevented by atropine, dicyclomine, pirenzepine, and hemicholinium‐3, but not by naloxone, atropine methyl bromide, and CGP 35348. In vitro experiments showed that the two investigated compounds amplified electrically evoked guinea pig ileum contractions. On the basis of the above data, it can be postulated that ET‐142 and SS‐20 exert their antinociceptive effect through a potentiation of central cholinergic transmission. Drug Dev. Res. 42:26–34, 1997. © 1997 Wiley‐Liss, Inc.