Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
9920904 | European Journal of Pharmacology | 2005 | 6 Pages |
Abstract
MD-354 (m-chlorophenylguanidine) is a 5-HT3/α2B-adrenoceptor ligand. Both receptors play a role in antinociception. In the mouse tail-flick assay, subcutaneously administered MD-354 was inactive as an analgesic. However, a combination of an inactive dose of clonidine (0.25 mg/kg) with an inactive dose of MD-354 (6 mg/kg) produced a substantial antinociceptive effect (maximal possible effect = 66%). Considering the 5-HT3 receptor partial agonist properties of MD-354, the analgesia enhancing effect of MD-354 on clonidine might be associated, at least in part, with its 5-HT3 receptor agonist or antagonist activity. Combinations of an inactive dose of clonidine (0.25 mg/kg) with 5-HT3 receptor antagonists (tropisetron, zacopride and ondansetron) were examined. Saline-like doses of tropisetron, zacopride and ondansetron significantly enhanced the antinociceptive effect of clonidine (combinations: maximal possible effect = 86%, 82% and 79% respectively), suggesting that MD-354 may enhance the analgesic actions of clonidine, at least in part, through a 5-HT3 receptor antagonist mechanism.
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Authors
Magorzata Dukat, Anna WesoÅowska,