A rapid, quantitative in vivo assay for narcotic antagonists.

Substance and alcohol actions/misuse Pub Date : 1984-01-01
M J Katovich, J W Simpkins, I C Song, N Bodor, R Tuttle
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Abstract

Tail skin temperature (TST) response of morphine-dependent rats was evaluated as a potential in vivo assay for the activity of narcotic antagonists. Dependency was produced in rats by repeated subcutaneous implantation of morphine-containing pellets and TST was evaluated by thermistor probes attached to the dorsal surface of the tail. TST was determined prior to and following administration of either naloxone (NAL: 0, 0.01, 0.1, 0.5 or 1.0 mg/kg body weight); naltrexone (NALT: 0.001, 0.005, 0.01, 0.02 or 0.1 mg/kg body weight); or 6-Desoxy-6-methylenenaltrexone (DM-NALT: 0.001, 0.005, 0.01, 0.02 or 0.1 mg/kg body weight). Each of the narcotic antagonists caused a dose-dependent increase in tail skin temperature in morphine dependent rats. The initial TST increase was observed by 5 minutes and the maximal TST response occurred 15 to 25 minutes after drug administration. For each drug evaluated, a linear relationship was observed between the dose and maximal change in TST and between the dose and the area under the TST response curve. Determination of ED50 for the TST response revealed the expected relative potency for the narcotic antagonists evaluated: DM-NALT greater than NALT greater than NAL. Thus, the TST-response test is a rapid and quantitative bioassay for the evaluation of compounds for narcotic antagonistic activity.

一种快速、定量的体内麻醉拮抗剂测定方法。
吗啡依赖大鼠的尾皮温度(TST)反应被评估为麻醉拮抗剂活性的潜在体内试验。通过反复皮下植入含吗啡微丸,大鼠产生依赖性,并通过附着在尾巴背表面的热敏电阻探针评估TST。在服用纳洛酮之前和之后测定TST (NAL: 0、0.01、0.1、0.5或1.0 mg/kg体重);纳曲酮(NALT: 0.001、0.005、0.01、0.02或0.1 mg/kg体重);或6-去氧基-6-亚甲曲酮(DM-NALT: 0.001, 0.005, 0.01, 0.02或0.1 mg/kg体重)。每一种麻醉拮抗剂引起吗啡依赖大鼠尾皮温度的剂量依赖性升高。最初TST升高的时间为5分钟,最大TST反应发生在给药后15 ~ 25分钟。对于所评估的每种药物,剂量与TST的最大变化之间以及剂量与TST反应曲线下面积之间存在线性关系。ED50对TST反应的测定揭示了所评估的麻醉拮抗剂的预期相对效力:DM-NALT大于NALT大于NAL。因此,tst反应试验是一种快速和定量的生物测定方法,用于评估化合物的麻醉拮抗活性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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