Roache J D, Griffiths R R
Drug Alcohol Depend. 1986 May;17(1):15-29. doi: 10.1016/0376-8716(86)90032-3.
The present study examined the effects of repeated administration of diazepam (DZ) and triazolam (TZ) on psychomotor performance and subject-rated drug liking. Subjects were 11 males (30-41 years) who had documented histories of drug abuse and who resided on a behavioral pharmacology research ward. Six subjects received 80 mg DZ every third day (3 subjects) or every sixth day (3 subjects) for a total of 3-6 dosing occasions and six subjects received TZ (2.0 or 3.0 mg) every second day (4 subjects) or every third day (2 subjects) for a total of 3-5 dosing occasions. The results showed that on the first dose occasion, the two drugs produced generally similar degrees of psychomotor impairment and subject-rated drug liking. Following the first DZ dose, subsequent doses produced less of an effect (i.e. single-dose tolerance). Across at least the first three dose occasions, progressive tolerance development was observed with DZ but no tolerance was observed with TZ. It is hypothesized that pharmacokinetic differences between DZ and TZ may account for the difference in the development of tolerance.
本研究考察了重复给予地西泮（DZ）和三唑仑（TZ）对精神运动能力和受试者评定的药物喜好程度的影响。受试者为11名男性（30 - 41岁），有药物滥用记录，居住在行为药理学研究病房。6名受试者每三天（3名受试者）或每六天（3名受试者）接受80毫克DZ，共给药3 - 6次；6名受试者每两天（4名受试者）或每三天（2名受试者）接受TZ（2.0或3.0毫克），共给药3 - 5次。结果显示，在首次给药时，两种药物产生的精神运动损害程度和受试者评定的药物喜好程度大致相似。首次给予DZ后，后续剂量产生的效果较小（即单剂量耐受）。至少在前三次给药过程中，观察到DZ有逐渐的耐受性发展，但未观察到TZ有耐受性。据推测，DZ和TZ之间的药代动力学差异可能解释了耐受性发展的差异。
