Frank G B
Arch Int Pharmacodyn Ther. 1975 Sep;217(1):4-17.
In drug interaction studies on intact mice it was found that naloxone (3mumoles/kg) antagonized the general central nervous system depressant effects of morphine or meperidine. Higher naloxone doses (0.3 and 0.4 mmoles/kg), like the fullagonists, potentiated the loss of the righting reflex produced by phenobarbital. Naloxone (0.3 to 14 muM) antagonized the depressant effects of morphine or meperidine on the compound action potential of frog's sartorius muscles in vitro. Higher naloxone concentration (ED20=0.3 mM, ED100=3.0mM), like the full agonists, depressed action potential production. These results show that high doses of naloxone can duplicate some effects of morphine or meperidine but at low doses it antagonizes the effects of the full agonists. This would suggest that naloxone is a partial agonist with a very low intrinsic activity. These results also indicate that there are opiate drug receptors on excitable cell membranes and that drug activation of these receptors inhibits action potential production.
在对完整小鼠进行的药物相互作用研究中发现，纳洛酮（3微摩尔/千克）可拮抗吗啡或哌替啶对中枢神经系统的一般抑制作用。较高剂量的纳洛酮（0.3和0.4毫摩尔/千克），与完全激动剂一样，可增强苯巴比妥引起的翻正反射消失。纳洛酮（0.3至14微摩尔）可拮抗吗啡或哌替啶对青蛙离体缝匠肌复合动作电位的抑制作用。较高浓度的纳洛酮（ED20 = 0.3毫摩尔，ED100 = 3.0毫摩尔），与完全激动剂一样，可抑制动作电位的产生。这些结果表明，高剂量的纳洛酮可复制吗啡或哌替啶的某些作用，但低剂量时它可拮抗完全激动剂的作用。这表明纳洛酮是一种内在活性非常低的部分激动剂。这些结果还表明，可兴奋细胞膜上存在阿片类药物受体，药物对这些受体的激活会抑制动作电位的产生。
