Sharpe L G
National Institute on Drug Abuse, Addiction Research Center, Baltimore, Maryland.
J Pharmacol Exp Ther. 1991 Mar;256(3):845-9.
The pharmacologic characteristics of a highly selective mu receptor agonist, sufentanil, were studied on the cat's pupillary responses (size, light reflex and fluctuations) measured with an infrared video pupillometer. The pupillary effects of sufentanil were also compared with those of morphine and clonidine, known mydriatics in the cat. Sufentanil (0.3-10 micrograms/kg i.v.) dose-dependently increased pupillary size and decreased light reflex and fluctuations. Naltrexone (10 micrograms/kg i.v.) pretreatment shifted the dose-response curve to the right by a factor of 26 for pupillary size, 9.5 for light reflex and 7.2 for fluctuations (nonvalid bioassay). Equivalent mydriatic doses of sufentanil (1 micrograms/kg), morphine (0.5 mg/kg) and clonidine (10 micrograms/kg) produced divergent effects on the light reflex and fluctuations. At these doses, morphine was more effective than sufentanil in inhibiting fluctuations. Clonidine was a more potent inhibitor of fluctuations but significantly enhanced the light reflex. Sufentanil (compared with morphine in a previous study) was 298 times more potent than morphine as a mydriatic, 100 times more potent in inhibiting the light reflex, and only slightly more potent in inhibiting fluctuations. These results indicate that separate neural mechanisms control the three pupillary components and that mu opioid receptors are more involved in mediating opiate-induced mydriasis than in inhibiting the light reflex and fluctuations in the cat.
使用红外视频瞳孔计测量猫的瞳孔反应(大小、光反射和波动),研究了高选择性μ受体激动剂舒芬太尼的药理学特性。还将舒芬太尼的瞳孔效应与猫体内已知的散瞳剂吗啡和可乐定进行了比较。静脉注射舒芬太尼(0.3 - 10微克/千克)可剂量依赖性地增加瞳孔大小,并降低光反射和波动。纳曲酮(静脉注射10微克/千克)预处理使瞳孔大小的剂量反应曲线右移26倍,光反射右移9.5倍,波动右移7.2倍(无效生物测定)。等效散瞳剂量的舒芬太尼(1微克/千克)、吗啡(0.5毫克/千克)和可乐定(10微克/千克)对光反射和波动产生不同的影响。在这些剂量下,吗啡在抑制波动方面比舒芬太尼更有效。可乐定是更强效的波动抑制剂,但显著增强了光反射。舒芬太尼(与先前研究中的吗啡相比)作为散瞳剂的效力比吗啡高298倍,在抑制光反射方面高100倍,在抑制波动方面仅略强。这些结果表明,不同的神经机制控制着瞳孔的三个组成部分,并且μ阿片受体在介导阿片类药物引起的散瞳方面比在抑制猫的光反射和波动方面更起作用。