Lawlor B A, Sunderland T, Mellow A M, Hill J L, Molchan S E, Murphy D L
Unit on Geriatric Psychopharmacology, National Institute of Mental Health, Bethesda, Md. 20892.
Arch Gen Psychiatry. 1989 Jun;46(6):542-9. doi: 10.1001/archpsyc.1989.01810060064010.
The serotonin agonist m-chlorophenylpiperazine (mCPP) was administered intravenously to 12 patients with Alzheimer's disease and ten age-matched controls. It produced distinct behavioral effects in both treatment groups; however, significantly greater responsivity to mCPP was found in patients with Alzheimer's disease than in controls in measures of psychomotor activation, restlessness, and perceptual abnormalities. Significant and similar increases in plasma prolactin and cortisol levels were found in both patients with Alzheimer's disease and controls following the administration of mCPP vs placebo. Furthermore, blood pressure and pulse changes following mCPP were not significantly different between the groups. Elderly controls, however, did show a significantly greater temperature response following mCPP than did patients with Alzheimer's disease. The overall cognitive effects of mCPP were minimal; however, mCPP produced significantly greater worsening in recent memory and knowledge memory in patients with Alzheimer's disease than in controls. These findings could not be explained by pharmacokinetic differences across populations, because plasma concentrations of mCPP were similar in patients with Alzheimer's disease and controls. The increased behavioral responsivity but unchanged neuroendocrine or other physiologic responsivity to mCPP may be related to damaged brain serotonin neurons or other neuronal systems that interact with serotonin neurons that have been found in postmortem and biopsy studies of patients with Alzheimer's disease.
对12名阿尔茨海默病患者和10名年龄匹配的对照者静脉注射血清素激动剂间氯苯哌嗪（mCPP）。在两个治疗组中它都产生了明显的行为效应；然而，在精神运动激活、烦躁不安和知觉异常的测量中，发现阿尔茨海默病患者对mCPP的反应性明显高于对照者。与安慰剂相比，在给予mCPP后，阿尔茨海默病患者和对照者的血浆催乳素和皮质醇水平均有显著且相似的升高。此外，两组之间mCPP后的血压和脉搏变化无显著差异。然而，老年对照者在给予mCPP后的体温反应比阿尔茨海默病患者显著更大。mCPP的总体认知效应很小；然而，mCPP在阿尔茨海默病患者中导致的近期记忆和知识记忆恶化比对照者显著更严重。这些发现无法用不同人群之间的药代动力学差异来解释，因为阿尔茨海默病患者和对照者的mCPP血浆浓度相似。对mCPP的行为反应性增加但神经内分泌或其他生理反应性未改变，可能与死后和活检研究中在阿尔茨海默病患者中发现的受损脑血清素神经元或其他与血清素神经元相互作用的神经元系统有关。
