The interaction of tetrahydroisoquinoline derivatives with antinociceptive action of morphine and oxotremorine in mice

To extend our earlier data on synergistic action of tetrahydroisoquinolines and morphine, we have investigated the analgesic effects of 1,2,3,4-tetrahydroisoquinoline (TIQ) and its 1-methyl-(1-MeTIQ) and N-methyl (N-MeTIQ) analogs on analgesia induced by morphine and oxotremorine. 1-MeTIQ and N-MeTIQ induced a moderate, delayed and prolonged analgesic action measured in the tail-flick test in CD-1 mice; 1-MeTIQ and TIQ prolonged the opiate (morphine, 2.5 mg/kg i.p.) analgesia while TIQ and N-TIQ potentiated cholinergic (oxotremorine, 0.02 mg/kg i.p.) analgesia. The involvement of the opioid and noradrenergic systems in this effect is discussed.