Tariot P N, Sunderland T, Weingartner H, Murphy D L, Cohen M R, Cohen R M
Arch Gen Psychiatry. 1986 Aug;43(8):727-32. doi: 10.1001/archpsyc.1986.01800080013002.
There have been conflicting reports on the effects of naloxone hydrochloride in patients with dementia of the Alzheimer type (DAT). In addition, none of the naloxone studies in DAT used doses of 2.0 mg/kg or more, the amount necessary to produce reliable cognitive and behavioral changes in young normal subjects. In a randomized, double-blind, placebo-controlled study, 12 patients with DAT were administered naloxone hydrochloride in doses of 5 micrograms/kg, 0.1 mg/kg, and 2.0 mg/kg, with detailed evaluation of its behavioral and cognitive effects using measures selected for their potential relevance to DAT and the known effects of blockade of endogenous opiate systems. None of the measures of motor performance, attention, memory, learning, or recognition showed improvement with naloxone. Increased inappropriate verbal productions were noted after 0.1 mg/kg of naloxone hydrochloride. Patients became irritably activated after this dose, which may account for the altered verbal behavior in this study and also for some of the changes suggesting cognitive improvement in prior studies. Differences in the sensitivity and dose dependency of the behavioral effects in patients with DAT compared with prior studies in young normal subjects merit further investigation.
关于盐酸纳洛酮对阿尔茨海默型痴呆（DAT）患者的影响，一直存在相互矛盾的报道。此外，在DAT患者中进行的纳洛酮研究均未使用2.0mg/kg或更高的剂量，而这是在年轻正常受试者中产生可靠的认知和行为变化所需的剂量。在一项随机、双盲、安慰剂对照研究中，12名DAT患者分别接受了5微克/千克、0.1毫克/千克和2.0毫克/千克剂量的盐酸纳洛酮，并使用因其与DAT的潜在相关性以及内源性阿片系统阻断的已知作用而选择的测量方法，对其行为和认知效果进行了详细评估。纳洛酮并未使运动表现、注意力、记忆、学习或识别等测量指标得到改善。在给予0.1毫克/千克盐酸纳洛酮后，出现了更多不适当的言语表达。服用该剂量后，患者变得烦躁不安，这可能解释了本研究中言语行为的改变，也解释了先前研究中一些提示认知改善的变化。与先前在年轻正常受试者中的研究相比，DAT患者行为效应的敏感性和剂量依赖性差异值得进一步研究。
