Hammond D L, Bloss J L
Department of Anesthesia and Critical Care, University of Chicago, IL 60637.
Eur J Pharmacol. 1993 Feb 9;231(2):281-5. doi: 10.1016/0014-2999(93)90461-p.
This study evaluated the antinociceptive activity of an opioid dipeptide arylalkylamide, SC-39566 (2,6-dimethyl-L-tyrosinyl-D-alanyl-(3-phenyl-l-propyl)- amide), in the Rhesus monkey using the discrete trial, intermittent shock titration paradigm. I.m. administration of doses ranging from 12 to 24 mg/kg produced a dose-dependent increase in escape threshold and a dose-dependent rightward shift in the frequency distribution of responses to suprathreshold electrocutaneous stimuli. Although equivalent with respect to efficacy, SC-39566 was only one-fourth to one-sixth as potent as morphine in this paradigm. This study is the first report of the antinociceptive activity of an opioid dipeptide arylalkylamide after systemic administration in the primate.
本研究采用离散试验、间歇性电击滴定范式,评估了阿片类二肽芳基烷基酰胺SC-39566(2,6-二甲基-L-酪氨酰-D-丙氨酰-(3-苯基-1-丙基)酰胺)在恒河猴中的抗伤害感受活性。肌肉注射12至24mg/kg剂量可使逃避阈值呈剂量依赖性增加,对阈上电刺激的反应频率分布呈剂量依赖性右移。尽管在疗效方面相当,但在该范式中,SC-39566的效力仅为吗啡的四分之一至六分之一。本研究是关于阿片类二肽芳基烷基酰胺在灵长类动物全身给药后抗伤害感受活性的首次报道。