Shimada A, Tsuda T, Yanagita T
Department of Pharmacology, Central Institute for Experimental Animals, Kawasaki, Japan.
Jpn J Pharmacol. 1988 Oct;48(2):185-93. doi: 10.1254/jjp.48.185.
The mechanism of antinociceptive interactions among morphine, cocaine and alcohol was studied in mice, guinea pigs and rabbits. In the tail-pressure test in mice, cocaine and alcohol alone showed almost no antinociceptive effects at doses up to 8 mg/kg, s.c., and 4 g/kg, respectively. Alcohol at 2 g/kg, i.g., also did not influence the effect of morphine, while cocaine at 4 mg/kg, s.c., significantly potentiated the antinociceptive effects of not only morphine but also pentazocine. In an analysis of serum and brain concentration levels of morphine in mice, when morphine and cocaine were simultaneously administered at 2 mg/kg, s.c., and 4 mg/kg, s.c., respectively, both serum and brain levels of morphine showed neither increase nor decrease in comparison with the levels in mice administered morphine alone. In myenteric plexus-longitudinal muscle preparations of isolated guinea pig ileum, 1 microM cocaine enhanced the agonistic effects of both pentazocine and ethylketocyclazocine. Furthermore, cocaine as well as ethylketocyclazocine showed naloxone-reversible agonistic effects in isolated rabbit vas deferens. These results indicate that cocaine may potentiate the antinociceptive effects of morphine and pentazocine by acting on the kappa-opioid receptors as an agonist.
在小鼠、豚鼠和兔子身上研究了吗啡、可卡因和酒精之间的抗伤害感受相互作用机制。在小鼠的尾压试验中，单独使用可卡因和酒精，分别在皮下注射剂量高达8毫克/千克和腹腔注射剂量高达4克/千克时，几乎没有抗伤害感受作用。腹腔注射2克/千克酒精也不影响吗啡的作用，而皮下注射4毫克/千克可卡因不仅能显著增强吗啡的抗伤害感受作用，还能增强喷他佐辛的抗伤害感受作用。在对小鼠血清和脑内吗啡浓度水平的分析中，当分别以皮下注射2毫克/千克和4毫克/千克的剂量同时给予吗啡和可卡因时，与单独给予吗啡的小鼠相比，血清和脑内吗啡水平均未升高或降低。在离体豚鼠回肠的肠肌丛-纵肌制备物中，1微摩尔可卡因增强了喷他佐辛和乙基酮环唑辛的激动作用。此外，可卡因以及乙基酮环唑辛在离体兔输精管中表现出纳洛酮可逆的激动作用。这些结果表明，可卡因可能作为激动剂作用于κ-阿片受体，从而增强吗啡和喷他佐辛的抗伤害感受作用。
