Pitts D K, Marwah J
Neuroscience Laboratory, Wayne State University, Detroit, Michigan.
J Pharmacol Exp Ther. 1988 Dec;247(3):815-23.
Agents known to influence adrenergic function were examined for their mydriatic effects in urethane-anesthetized rats. Both the direct acting adrenergic agonist, clonidine, and the "indirect" acting agonists, cocaine, desipramine and amphetamine elicited mydriatic responses. The polar alpha-2 adrenoceptor agonist, 4-hydroxyclonidine, did not elicit a mydriatic response when administered systemically; however, it did produce a pronounced mydriatic response when administered i.c.v. Inasmuch as the selective lipophilic alpha-2 adrenoceptor antagonist, yohimbine, but not the polar alpha adrenoceptor antagonist, phentolamine, reversed the mydriatic effects of clonidine and cocaine, these data suggest that centrally located alpha-2 adrenoceptors elicit the above mydriatic response. The direct acting alpha-2 adrenoceptor agonists, clonidine (i.v.) and 4-hydroxyclonidine (i.c.v.), were the most efficacious of the agents studied in eliciting the mydriatic response. The indirect acting agents, amphetamine, desipramine and cocaine, were less efficacious. The rank order potency (ED-50) of these drugs was as follows: clonidine greater than desipramine greater than cocaine = amphetamine. The mydriatic effects of cocaine were attenuated by yohimbine and reserpine pretreatments. In addition, the local anesthetic, procaine, and the polar cocaine analog, cocaine methiodide, were significantly less efficacious than cocaine. These results suggest that cocaine elicits mydriasis by indirectly acting at central and postsynaptically located alpha-2 adrenoceptors.
研究了已知影响肾上腺素能功能的药物对氨基甲酸乙酯麻醉大鼠的散瞳作用。直接作用的肾上腺素能激动剂可乐定以及“间接”作用的激动剂可卡因、地昔帕明和苯丙胺均引起散瞳反应。极性α-2肾上腺素能受体激动剂4-羟基可乐定全身给药时未引起散瞳反应；然而，脑室内给药时却产生了明显的散瞳反应。由于选择性亲脂性α-2肾上腺素能拮抗剂育亨宾而非极性α肾上腺素能拮抗剂酚妥拉明可逆转可乐定和可卡因的散瞳作用，这些数据表明中枢性α-2肾上腺素能受体引起上述散瞳反应。直接作用的α-2肾上腺素能激动剂可乐定（静脉注射）和4-羟基可乐定（脑室内注射）是所研究药物中引起散瞳反应最有效的药物。间接作用药物苯丙胺、地昔帕明和可卡因的效果较差。这些药物的效价顺序（半数有效剂量）如下：可乐定＞地昔帕明＞可卡因=苯丙胺。育亨宾和利血平预处理可减弱可卡因的散瞳作用。此外，局部麻醉药普鲁卡因和极性可卡因类似物可卡因甲碘化物的效果明显低于可卡因。这些结果表明，可卡因通过间接作用于中枢和突触后α-2肾上腺素能受体引起散瞳。
