5-HT-uptake inhibition potentiates antinociception induced by morphine, pethidine, methadone and ketobemidone in rats.

The effect of the specific 5-HT-uptake inhibitor citalopram on the antinociception induced by morphine, pethidine, methadone and ketobemidone was examined in rats by means of the hot plate test. Further the 5-HT-uptake-inhibiting potency of these opioid-receptor stimulants was examined in vitro in rat brain synaptosomes. In doses devoid of antinociceptive activity, citalopram in a dose-dependent manner potentiated the antinociception induced by the four opioid analgesics. The potentiation of the ketobemidone-induced antinociception was not influenced by the spasmolytic agent A 29 (N,N-dimethyl-3,3-diphenyl-1-methylallylamine) which together with ketobemidone constitutes the active substances in Ketogan. The 5-HT-uptake-inhibiting potencies of the opioid receptor stimulants were from 21 to more than 56000 times lower than that of citalopram, the order of potency being methadone greater than pethidine greater than ketobemidone greater than morphine. The results support the suggested role of 5-HT in morphine-induced antinociception and indicate a similar role in the antinociceptive effect induced by other opioid-receptor stimulants.