EFFECTS OF NARCOTIC ANALGESICS ON THE UPTAKE AND RELEASE OF 5‐HYDROXYTRYPTAMINE IN RAT SYNAPTOSOMAL PREPARATIONS

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Abstract
1 The effects of various narcotic analgesics on the uptake and release of labelled 5-hydroxytrypta-mine (5-HT) in brain and spinal cord synaptosomes were investigated. 2 Methadone was most active in inhibiting 5-HT uptake (IC50 2.5 × 10−7m). Levorphanol also inhibited 5-HT uptake to a large extent (IC50 8.8 × 10−7m) while dextrorphan, pethidine and pentazocine showed much less activity. Etorphine and morphine had virtually no such activity, with IC50s higher than 10−4 and 10−3m respectively. 3 The same order of potency as ′5-HT releasers' was found when radioactivity was measured in [3H]-5-HT preloaded synaptosomal pellets incubated for 20min with the various narcotics. Methadone, like chlorimipramine, showed a significant effect at a concentration of 10−7m while morphine, at a concentration of 10−4m, had no effect. 4 When 5-HT release was studied by a perfusion technique, which largely prevents reuptake of the released amine, only fenfluramine, an anorectic agent proposed as a 5-HT releaser, significantly increased spontaneous 5-HT release. These data suggest that the apparent 5-HT release induced by various narcotics in traditional incubation techniques may largely depend on their ability to interfere with neurotransmitter reuptake mechanisms. 5 The effects of the various narcotics on 5-HT uptake have no relationship to their relative potency as analgesics in the rat. In the light of their poor effectiveness as 5-HT releasers, it can be concluded that mechanisms other than 5-HT uptake inhibition and release are probably involved in the analgesic effects of these compounds in intact animals.