四氢原小檗碱同类物缓解吗啡戒断症状作用的实验研究

目的··：观察四氢原小檗碱同类物（ＴＨＰＢｓ）对吗啡依赖小鼠和大鼠戒断症状的影响。方法··：以连续递增剂量方式ｓｃ盐酸吗啡，建立吗啡依赖小鼠和大鼠模型，ｉｐＴＨＰＢｓ２０ｍｉｎ后，用环丙羟丙吗啡（小鼠５ｍｇ·ｋｇ－１，大鼠２ｍｇ·ｋｇ－１，ｉｐ）催瘾。结果··：小鼠分别ｉｐｌ－四氢巴马汀（ｌ－ＴＨＰ，１５，３０，６０ｍｇ·ｋｇ－１）、ｌ－千金藤啶碱（ｌ－ＳＰＤ，１５，３０，６０ｍｇ·ｋｇ－１）和ｄｌ－四氢巴马汀（ｄｌ－ＴＨＰ，１５，３０，６０ｍｇ·ｋｇ－１）可显著抑制其跳台反应，降低跳台次数，减少体重下降。大鼠分别ｉｐｌ－ＴＨＰ（１０，２０，４０ｍｇ·ｋｇ－１）和ｄｌ－ＴＨＰ（１０，２０，４０ｍｇ·ｋｇ－１）能够抑制１ｈ体重下降，大大改善戒断时的行为表现，减轻腹泻和流涎，症状评分随剂量增加而下降。ｌ－ＳＰＤ抑制大鼠戒断症状作用虽无剂量依赖关系，但１０ｍｇ·ｋｇ－１却可减轻大鼠２４ｈ体重下降。结论··：ＴＨＰＢｓ可缓解吗啡依赖小鼠和大鼠戒断症状，可能具有临床应用价值。

EXPERIMENTAL STUDY OF TETRAHYDROPROTOBERBERINES INHIBITING MORPHINE WITHDRAWAL SYNDROMES

Objective:To study the effects of tetrahydroprotoberberines(THPBs) on the withdrawal syndromes in morphine-dependent mice and rats. Method: Mice and rats were administered (sc) with morphine hydrochloride in increasing doses.Then the withdrawal syndromes precipitated by diprenorphine (5 mg·kg-1 in mice, 2 mg·kg-1 in rats) were observed 20 minutes after THPBs were given (ip). Result: l-THP, dl-THP and l-SPD,at dose 15, 30, 60 mg·kg-1 (ip), respectively, were able to inhibit mice incidence and freguency of jumping and body weight loss significantly. Similarly, behavioral withdrawal syndromes of rats, i.e.enraging, teeth chattering, wet dog shakes,jumping etc, were greatly depressed; diarrhea, salivation and weight loss(1h)were also reduced by l-THP and dl-THP(10, 20, 40 mg·kg-1,ip). Abstinence syndrome scores were decreased as doses were increased. Furthermore,l-SPD 10 mg·kg-1 could reduce rat weight loss at 24 hour, although its effects inhibiting withdrawal syndromes were not dose-related. Conclusion:THPBs could inhibit abstinence syndroms in morphine-dependent mice and rats,which suggested that it may be useful in clinical detoxification.