Antagonism of morphine-induced antinociception by tetrandrine is dependent on serotonergic mechanisms.
'Tetrandrine (TET), a non-specific calcium antagonist, inhibited morphine-induced antinociception in the tail-flick test in mice. This study was undertaken to assess the mechanism of the antagonism of morphine-induced antinociception by TET. Morphine-induced antinociception was prevented by pretreatment with TET in the tail-flick but not in the tail-pinch tests carried out in mice and this antagonism was abolished by pretreatment of a serotonin precursor, 5-hydroxytryptophan (5-HTP), but not by the pretreatment of a noradrenaline precursor, L-dihydroxyphenylalanine (L-DOPA), in the tail-flick test. These results indicate that serotonergic mechanisms are involved in the antagonism of morphine-induced antinociception by TET. On the other hand, the development of morphine-induced analgesic tolerance was not prevented by TET. This result, in agreement with other reports, also indicates the possible dissociation of morphine analgesic effect from its tolerance-inducing effect. In addition, TET suppressed the 5-hydroxytryptamine (5-HT)-induced head twtch response. This result provides additional evidence that TET may modulate serotonergic function and the antagonism of morphine-induced antinociception by TET is dependent on serotonergic mechanisms.
Zhang
Y H
YH
Department of Pharmacology, The School of Basic Medicine, Beijing University, China.
Fang
L H
LH
D000470:Alkaloids / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000037:antagonists & inhibitors*; D000818:Animals; D044182:Benzylisoquinolines; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000037:antagonists & inhibitors*; D010146:Pain / Q000517:prevention & control; D010147:Pain Measurement / Q000187:drug effects; D012701:Serotonin / Q000502:physiology*; D013623:Tail / Q000187:drug effects / Q000502:physiology
D000470:Alkaloids; D000701:Analgesics, Opioid; D044182:Benzylisoquinolines; D002121:Calcium Channel Blockers; C009438:tetrandrine; D012701:Serotonin; D009020:Morphine