ANALGESIC EFFECTS OF MORPHINE AND ITS MET ABOLITES AFTER INTRACEREBROVENTRICULAR ADMINISTRATION

Intraventricular morphine administration is indicated, in some selecte d cases, to alleviate intractable cancer pain. Our pharmacokinetics da ta in cerebro-spinal fluid allowed us to formulate the theory of ''Fro nt de Recrutement''. Then we were able to determine in cisternal and v entricular cerebrospinal fluid the morphine 6-glucuronide concentratio ns. Morphine 6-glucuronide is the main analgesic metabolite of morphin e and its presence in cerebro-spinal fluid could be due to a metabolis m of morphine in the central nervous system. Our animal studies showed that the analgesic activity of morphine 6-glucuronide was 27 to 67 ti mes higher than that of morphine. By demonstrating the 6-monoacetyl mo rphine potency (analgesic metabolite of heroin that is 20 times more p otent than morphine), we showed the involvement of the 6 position in t he analgesic effect of these opioids. When we compared the morphine-6 concentrations in human cerebro-spinal fluid with the analgesic potenc y of this metabolite, the morphine-6 glucuronide was responsible of 33 % to 67 % of the supra-spinal analgesic effect. As heroin, morphine m ust be considered as a precursor whose metabolites have pharmacologic effects.