Haase Claus G, Becka Michael, Kuhlmann Jochen, Wensing Georg
Institute of Clinical Pharmacology, Pharma Research Center, Bayer HealthCare AG, D-42096 Wuppertal, Germany.
Prog Neuropsychopharmacol Biol Psychiatry. 2005 May;29(4):549-56. doi: 10.1016/j.pnpbp.2005.01.006.
Assessment of cerebral blood flow velocities (CBFV) can be used as a non-invasive tool to evaluate specific drug effects, like caffeine (CAF), acetazolamide (AA) as well as cognition. Their influences on each others CBFV were evaluated in detail, using a randomized, double-blind, double-dummy, placebo-controlled three-fold cross-over study design in 18 right-handed healthy male volunteers. CBFV (maximal, mean, minimal) and pulsatility index of both middle cerebral arteries were recorded by transcranial Doppler ultrasound simultaneously, during a verbal memory test, oral CAF, intravenous AA or placebo. AA led to increase in CBFV of 25-32%. Caffeine resulted in decreased V(mean) and V(min) of 10-13%. Cognitive stimulation resulted in a slight increase of CBVF of about 4%, but was overruled by effects of AA and CAF. We conclude that pharmacological effects can easily be assessed by TCD during clinical pharmacological studies of vasoactive drugs. However intraindividual variability and effects of neuropsychological stimulation needs to be taken into account.
脑血流速度(CBFV)评估可作为一种非侵入性工具,用于评估特定药物的作用,如咖啡因(CAF)、乙酰唑胺(AA)以及认知功能。使用随机、双盲、双模拟、安慰剂对照的三交叉研究设计,在18名右利手健康男性志愿者中,详细评估了它们对彼此CBFV的影响。在言语记忆测试、口服CAF、静脉注射AA或安慰剂期间,通过经颅多普勒超声同时记录双侧大脑中动脉的CBFV(最大值、平均值、最小值)和搏动指数。AA使CBFV增加25 - 32%。咖啡因使V(平均值)和V(最小值)降低10 - 13%。认知刺激使CBVF轻微增加约4%,但被AA和CAF的作用所掩盖。我们得出结论,在血管活性药物的临床药理学研究中,经颅多普勒(TCD)可轻松评估药物效应。然而,个体内变异性和神经心理刺激的影响需要考虑在内。