Campbell I C, McKernan R M, Smokcum R W, Stephenson J D, Weeramanthri T B
Neuropharmacology. 1984 Dec;23(12A):1385-8. doi: 10.1016/0028-3908(84)90077-7.
In rat brain, the number of beta-adrenoceptors and activity of noradrenaline-dependent adenylate cyclase were examined after treatment with desipramine (7.5 mg kg-1 day-1) for three days alone or in combination with the alpha 2-adrenoceptor antagonist, yohimbine (2 mg kg-1 12 hr-1), or with phenoxybenzamine (7.5 mg kg-1 day-1), which is a more potent inhibitor of alpha 1 than alpha 2-adrenoceptors. The only treatment which significantly decreased the specific binding of the beta-adrenoceptor antagonist, [3H]dihydroalprenolol was the combination of desipramine with yohimbine. Desipramine alone and desipramine with yohimbine also significantly reduced the formation of cyclic AMP in response to incubation with noradrenaline, the response to the drug combination being accounted for by addition of the individual effects of the drugs. The results showed that decreases in the activity of noradrenaline-dependent adenylate cyclase could become apparent before decreases in beta-adrenoceptor numbers. Whether these rapid changes in noradrenaline-dependent adenylate cyclase or in numbers of beta-adrenoceptors which are produced by combination of desipramine with an alpha 2-adrenoceptor antagonist, are of therapeutic value remains to be elucidated.
在大鼠脑中，单独给予地昔帕明（7.5毫克/千克/天，持续三天）或与α2-肾上腺素能受体拮抗剂育亨宾（2毫克/千克，每12小时一次）或与苯氧苄胺（7.5毫克/千克/天）联合使用后，检测β-肾上腺素能受体的数量以及去甲肾上腺素依赖性腺苷酸环化酶的活性。苯氧苄胺是一种对α1-肾上腺素能受体的抑制作用强于α2-肾上腺素能受体的药物。唯一能显著降低β-肾上腺素能受体拮抗剂[3H]二氢阿普洛尔特异性结合的处理是地昔帕明与育亨宾的联合使用。单独使用地昔帕明以及地昔帕明与育亨宾联合使用也显著降低了与去甲肾上腺素孵育后环磷酸腺苷的生成，药物联合使用的反应是由两种药物各自的作用相加所致。结果表明，去甲肾上腺素依赖性腺苷酸环化酶活性的降低可能在β-肾上腺素能受体数量减少之前就已明显显现。地昔帕明与α2-肾上腺素能受体拮抗剂联合使用所产生的去甲肾上腺素依赖性腺苷酸环化酶或β-肾上腺素能受体数量的这些快速变化是否具有治疗价值仍有待阐明。
