N-desmethyldiazepam physical dependence in dogs.
N-desmethyldiazepam physical dependence in dogs.
复制标题
N-去甲基地西泮对狗的身体依赖性。
DOI：
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发表时间：
1985
影响因子：
3.5
通讯作者：
T. Pruitt
中科院分区：
文献类型：
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作者：
L. McNicholas;W. Martin;T. Pruitt
通过外科手术植入慢性胃瘘的犬，长期给予N-去甲基安定(32 mg/kg/d)，分4个剂量给药，以达到与依赖地西潘(60 mg/kg/d)犬相当的血浆N-去甲基安定浓度。研究了N-去甲基安定戒断的时间进程，从达到稳定水平后不少于2周开始。突然停用N-去甲基安定后观察到的戒断综合征与安定戒断综合征相似，但在几个重要方面有所不同。在安定依赖的狗中，在停药非常早的时候(大约在最后一剂安定后1-2小时)有一次短暂的震颤，这在N-去甲基安定依赖的狗中看不到。与安定依赖犬相比，N-去甲基安定依赖犬更容易出现戒断症状，如震颤、热脚走路、抽搐和抽搐，食物和水的摄入量减少，体重也减少。依赖N-去甲基安定的狗的整体戒断强度，通过地西潘戒断量表来衡量，比依赖劳拉西潘或地西潘的狗更大。依赖安定或依赖N-去甲基安定的狗的血浆中N-去甲基安定和奥沙西潘的浓度几乎相同，而在依赖地西潘或劳拉西潘的狗中，N-去甲基地西潘或劳拉西潘的血浆浓度分别高出4到10倍。此外，N-脱甲基地西潘和奥沙西潘的血浆浓度下降速度比地西潘和劳拉西潘的下降速度慢得多。这些结果表明，对安定的身体依赖是由N-脱甲基安定的积累和作用造成的。
Dogs, surgically implanted with a chronic gastric fistula, were chronically dosed with N-desmethyldiazepam (32 mg/kg/day) in four divided doses to attain N-desmethyldiazepam plasma levels comparable to those observed in dogs dependent on diazepam (60 mg/kg/day). The time course of N-desmethyldiazepam abstinence was studied, beginning not less than 2 weeks after stabilization levels had been achieved. The abstinence syndrome observed after abrupt discontinuation of N-desmethyldiazepam was similar to the diazepam abstinence syndrome but differed in several important aspects. In diazepam-dependent dogs, there was a short burst of tremor very early in withdrawal (approximately 1-2 hr after the last dose of diazepam) that was not seen in N-desmethyldiazepam-dependent dogs. Signs of abstinence such as tremor, hot foot walking and twitches and jerks were more frequently observed in N-desmethyldiazepam-dependent dogs than in diazepam-dependent dogs as were decreases in food and water intake and in body weight. The overall intensity of abstinence, as measured by the Diazepam Withdrawal Abstinence Scale, was greater in N-desmethyldiazepam-dependent dogs than in dogs dependent on either lorazepam or diazepam. Plasma levels of N-desmethyldiazepam and oxazepam were nearly equal in dogs dependent on diazepam or on N-desmethyldiazepam and were 4 to 10 times greater than the plasma levels of diazepam or lorazepam in diazepam- or lorazepam-dependent dogs, respectively. Furthermore, the plasma levels of N-desmethyldiazepam and oxazepam declined much more slowly than the levels of diazepam and lorazepam. These results suggest that physical dependence on diazepam is caused by the accumulation and actions of N-desmethyldiazepam.(ABSTRACT TRUNCATED AT 250 WORDS)