Study On The Effects Of Caulis Sinomenii And Sinomenine On The Morphine-dependent Syndromes

Objective : To study on the detoxification effects of Caulis Sinomenii and sinomenine on the morphine-dependent withdrawal syndromes. Methods : By establishing the models of morphine-dependent mice, rats and the isolated ileum of guinea pig, the restraining effects of-Caulis Sinomenii and sinomenine on the withdrawal syndromes in the morphine dependent isolated ileum of guenea pig, morphine-abstinent mice and rats were observed; The rats' hypothalamic monoamine neurotransmitters such as noradrenaline(NA), dopamine (DA) , 5-Hydroxytryptamine (5-HT) were tested by fluorospectrophotometry. The effect of sinomenine on intracellular calcium level was detected by Fluo-3-AM measurements using a laser scanning confocal microscopy(LSCM) in the morphine-dependent human neuroblastemar SK-N-SH cells line. Morphine-dependent neuronal cells were cultured in RPMI1640 medium(containing 10"5mol morphine). A biased procedure induced the strong place preference. The effect of sinomenine on the rewarding property of morphine was observed using a conditioned place preference paradigm in mice. Meanwhile, the change of cAMP content in cerebral cortex was measured by the radioimmunoassay(RIA). A clinical study on compound Qing Feng Teng(Co.QFT) treating 186 cases of heroin addicts was used to investigate the detoxification effects of Caulis Sinomenii. Results Caulis Sinomenii and sinomenine could inhibit the naloxone(Nal)-precipitated withdrawal syndrome in of the morphine-dependent isolated ileum guinea pig, relieve withdrawal syndromes in morphine dependent mice and rats, renew mice's body weight. Sinomenine could decrease the contents of neurotransmitters in the rats' brain." Intracellular calcium level in morphine-dependent cells by naloxone-precipitated was remarkably higher than control ones. Sinomeninecould prevent this effect. Sinomenine effectively suppressed the acquisition of morphine-induced place preference in mice and reduced the contents of cAMP in cerebral cortex of mice. Co.QFT was more effective than Lof in treating acute opiate withdrawal syndrome. The adverse reactions of Co. QFT were slight and it was safe in the clinical using. Conclusion (1) Caulis Sinomenii and sinomenine had curative effects on morphine-depedent withdrawal syndromes, which mechanism may relate to inhibiting neurotransmitters. (2) The effect of sinomenine on tolerant nerve cells demonstrated that its detoxification mechanism was linked with regulation on the calcium level in the morphine-dependent cells. (3) Sinomenine could eliminate the acquisition of morphine-induced place preference in mice and reduce the contents of cAMP in the mouse cerebral cortex. Caulis Sinomenii and sinomenine could be used in treating opiate withdrawal syndrome and psychological dependence. (4) Co.QFT was effective in treating opiate withdrawal and psychological dependence syndromes.