Abstract
Oral methylnalorphine (methylnalorphinium) caused a dose-dependent selective inhibition of inflammatory hyper-algesia (measured in the rat by a modified version of the Randall-Selitto test) without affecting the oedema. When subcutaneously injected, repeated doses of morphine for 5 days caused progressive analgesic tolerance. Tolerance was not observed after similar treatment with methylnalorphinium or methylmorphinium. Animals displaying analgesic tolerance to systemic morphine did not exhibit tolerance to the local (intraplantar) injection of morphine, methylnalorphinium or methylmorphinium. In contrast with nalorphine and other opiates, methylnalorphinium did not reduce intestinal transit in mice. Methylnalorphinium, a mixed opiate agonist-antagonist devoid of central effects, might be considered the prototype of an ideal peripheral analgesic since it was orally active, did not affect intestinal transit and did not cause analgesic tolerance.
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