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EFFECTS OF NARCOTIC ANALGESICS ON THE UPTAKE AND RELEASE OF 5‐HYDROXYTRYPTAMINE IN RAT SYNAPTOSOMAL PREPARATIONS
Author(s) -
MENNINI TIZIANA,
PATACCINI R.,
SAMANIN R.
Publication year - 1978
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1978.tb08643.x
Subject(s) - levorphanol , chemistry , pentazocine , etorphine , pharmacology , dextrorphan , reuptake , potency , morphine , anorectic , serotonin , desipramine , fenfluramine , opioid , dextromethorphan , endocrinology , (+) naloxone , in vitro , biochemistry , antidepressant , medicine , body weight , receptor , hippocampus
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 (IC 50 2.5 × 10 −7 m ). Levorphanol also inhibited 5‐HT uptake to a large extent (IC 50 8.8 × 10 −7 m ) while dextrorphan, pethidine and pentazocine showed much less activity. Etorphine and morphine had virtually no such activity, with IC 50 s higher than 10 −4 and 10 −3 m respectively. 3 The same order of potency as ′5‐HT releasers' was found when radioactivity was measured in [ 3 H]‐5‐HT preloaded synaptosomal pellets incubated for 20min with the various narcotics. Methadone, like chlorimipramine, showed a significant effect at a concentration of 10 −7 m while morphine, at a concentration of 10 −4 m , 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.