Effect of acute and chronic tramadol on [3H]-norepinephrine-uptake in rat cortical synaptosomes.
1 Tramadol hydrochloride is a centrally acting opioid analgesic whose efficacy and potency is only five to ten times lower than that of morphine. Opioid, as well as non-opioid mechanisms, may participate in the analgesic activity of tramadol. 2 [3H]-NE uptake in isolated rat cortical synaptosomes was studied in the presence of tramadol, desipramine, methadone, and morphine. Desipramine and tramadol inhibited synaptosomal [3H]-NE uptake with apparent Kis of 7.3 +/- 0.66 and 1.4 +/- 0.0045 microM, respectively. Methadone was active at a 10-fold higher concentration (Ki: 87 +/- 5.6 microM). In contrast, morphine essentially failed to inhibit [3H]-5-HT uptake (Ki: 0.75 +/- 0.40 M). 3 Methadone, morphine, and tramadol were active in the hot plate test with ED50s of 6.2, 9.3, and 40 mg kg-1, respectively. 4 [3H]-NE uptake was examined in synaptosomes prepared from rats 30 min after receiving a single dose of morphine, methadone or tramadol. Only tramadol (31 mg kg-1, i.p.) decreased uptake of the transmitter, with an ED50 equal to that in the hot plate test. 5 Animals were chronically treated for 15 days with increasing doses of tramadol (20 to 125 mg kg-1, i.p.). Twenty-four hours after the last drug injection, a challenge dose of tramadol (40 mg kg-1, i.p.) was administered. Chronic tramadol was still able to reduce [3H]-NE uptake by 35%. 6 These results further support the hypothesis that [3H]-NE uptake inhibition may contribute to the antinociceptive effects of tramadol. The lack of tolerance in [3H]-NE uptake, together with the absence of behavioural alteration after chronic tramadol treatment proposes that tramadol holds potential over classical opioids in the treatment of pain disorders.
Franceschini
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D
Department of Pharmacology, University of Padua, Italy.
Lipartiti
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M
Giusti
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P
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013574:Synaptosomes / Q000502:physiology; D014147:Tramadol / Q000494:pharmacology*; D014316:Tritium
D000701:Analgesics, Opioid; D014316:Tritium; D014147:Tramadol; D009638:Norepinephrine