Nishida N, Chiba S
Drug Safety Research Laboratories, Takeda Chemical Industries, Ltd., Osaka, Japan.
J Toxicol Sci. 1991 May;16(2):75-86. doi: 10.2131/jts.16.75.
The novel enkephalin analog Tyr-D-Met (O)-Gly-EtPhe-NHNHCOCH3 . AcOH (EK-399) was examined for psychic dependence potential by a self-administration test in rats. Five groups of experimentally naive rats were given an intravenous dose of EK-399 (0.032, 0.064 or 0.125 mg/kg), morphine HCl (0.5 mg/kg) or cocaine HCl (0.5 mg/kg) via a cannula implanted in the jugular vein when they pressed a lever. No animals initiated self-administration of EK-399 in the first 3 or 4 weeks of the experimental period. In contrast, almost all of the animals receiving morphine or cocaine initiated a high rate of self-administration within 1 or 2 weeks. However, when the doses of EK-399 were subsequently decreased, 4 of the 10 animals increased their rate of self-administration slightly. Furthermore, an increase in the rate of EK-399 self-administration was observed in 1 of 4 rats made physically dependent on EK-399. These results suggest that EK-399 has a very weak reinforcing effect on drug-taking behavior, which is slightly enhanced by the development of physical dependence on the compound, and it may possess a low psychic dependence potential.
通过大鼠自我给药试验，对新型脑啡肽类似物酪氨酰-D-蛋氨酸（O）-甘氨酰-乙苯丙氨酸-肼基甲酸甲酯·醋酸（EK-399）的精神依赖性潜力进行了研究。五组初次进行实验的大鼠，在按压杠杆时，通过植入颈静脉的套管静脉注射剂量为0.032、0.064或0.125毫克/千克的EK-399、盐酸吗啡（0.5毫克/千克）或盐酸可卡因（0.5毫克/千克）。在实验期的前3或4周内，没有动物开始自我注射EK-399。相比之下，几乎所有接受吗啡或可卡因的动物在1或2周内开始了高频率的自我给药。然而，当EK-399的剂量随后降低时，10只动物中有4只略微提高了自我给药率。此外，在4只对EK-399产生身体依赖性的大鼠中，有1只出现了EK-399自我给药率的增加。这些结果表明，EK-399对药物摄取行为的强化作用非常弱，对该化合物的身体依赖性的发展会使其略有增强，并且它可能具有较低的精神依赖性潜力。
