[Analgesic effect of morphine and its metabolites administered by an intracerebroventricular route].
Intraventricular morphine administration is indicated, in some selected cases, to alleviate intractable cancer pain. Our pharmacokinetics data in cerebro-spinal fluid allowed us to formulate the theory of "Front de Recrutement". Then we were able to determine in cisternal and ventricular cerebrospinal fluid the morphine 6-glucuronide concentrations. Morphine 6-glucuronide is the main analgesic metabolite of morphine and its presence in cerebro-spinal fluid could be due to a metabolism of morphine in the central nervous system. Our animal studies showed that the analgesic activity of morphine 6-glucuronide was 27 to 67 times higher than that of morphine. By demonstrating the 6-monoacetyl morphine potency (analgesic metabolite of heroin that is 20 times more potent than morphine), we showed the involvement of the 6 position in the analgesic effect of these opioids. When we compared the morphine-6 concentrations in human cerebro-spinal fluid with the analgesic potency of this metabolite, the morphine-6 glucuronide was responsible of 33% to 67% of the supra-spinal analgesic effect. As heroin, morphine must be considered as a precursor whose metabolites have pharmacologic effects.
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Département de Diagnostic et de traitement de la douleur, Hôpital Lariboisière, Paris.
D000701:Analgesics, Opioid / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D006801:Humans; D007276:Injections, Intraventricular; D009020:Morphine / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D009022:Morphine Derivatives / Q000493:pharmacokinetics / Q000494:pharmacology*
D000701:Analgesics, Opioid; D009022:Morphine Derivatives; C035349:morphine-6-glucuronide; D009020:Morphine
Etudes de l'effet analgésique de la morphine et de ses métabolites administrés par voie intracérébro-ventriculaire.