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Eur J Pharmacol. 1988 Feb 9;146(2-3):223-8.

Peripheral analgesic action of clonidine: mediation by release of endogenous enkephalin-like substances.

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1
Department of Pharmacology, University of Minas Gerais, Brazil.

Abstract

Clonidine analgesia was tested on the hyperalgesia induced by intraplantar injection of prostaglandin E2 or carrageenin. The antinociceptive effect of clonidine was dose-dependent and was abolished by local administration of the selective alpha 2-adrenoceptor blocker, yohimbine or of the opioid antagonists naloxone or quaternary nalorphine. St-91, a clonidine analog which does not cross the blood-brain barrier also promoted significant antinociception. Repeated administration of drugs possessing a central mechanism of analgesic action leads to the development of tolerance in this test. Significant analgesic tolerance was observed following repeated (5 days) morphine (8 mg/kg) or high doses of clonidine (0.5 mg/kg). In contrast, no tolerance was detected to the analgesic effect of low doses of clonidine (0.15 mg/kg) or of St-91 (0.5 mg/kg). These results suggest that, in addition to its central analgesic action, clonidine can induce peripheral antinociception by an alpha 2-adrenoceptor-mediated local release of enkephalin-like substances.

PMID:
3163552
DOI:
10.1016/0014-2999(88)90296-8
[Indexed for MEDLINE]

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