Salem S A, McDevitt D G
Clin Pharmacol Ther. 1983 Jan;33(1):52-7. doi: 10.1038/clpt.1983.7.
The central effects of atenolol, a cardioselective beta-adrenoceptor antagonist, were investigated in six healthy men. Two flash-fusion threshold (2FFT), simple reaction time (SRT), digital copying (DCT), symbol-digit modalities (SDMT), and Gibson's spiral maze tests (GSMT) and mood rating scales for tension, alertness, depression, detachment, and anxiety were used. Each subject took 50, 100, 200, and 400 mg atenolol and identical placebo orally in a randomized, double-blind, crossover study and the psychomotor tests were performed at 0, 2, 3, 5, and 8 hr. 2FFT was prolonged at 3 hr after all doses and at 2 and 5 hr with 100, 200, and 400 mg. The maximum effect was achieved with 200 mg and mean 2FFT correlated with mean plasma atenolol concentration. SRTs were prolonged after all doses at between 2 and 5 hr. The DCT and the retest gain of the SDMT were both lower than after placebo at 2 hr with 100, 200, and 400 mg. The time taken to perform the GSMT was not altered by active drug, but the number of errors was lower at 2 hr with 100 and 200 mg. The self-rating mood scales showed a subjective decrease in tension 2 hr after 400 mg. The results show that atenolol exerts central effects in man.
在六名健康男性中研究了心脏选择性β-肾上腺素能受体拮抗剂阿替洛尔的中枢效应。使用了两项闪光融合阈值(2FFT)、简单反应时间(SRT)、数字抄写(DCT)、符号数字模式(SDMT)、吉布森螺旋迷宫测试(GSMT)以及紧张、警觉、抑郁、超脱和焦虑的情绪评定量表。在一项随机、双盲、交叉研究中,每位受试者口服50、100、200和400毫克阿替洛尔以及相同的安慰剂,并在0、2、3、5和8小时进行心理运动测试。所有剂量给药后3小时以及100、200和400毫克剂量给药后2小时和5小时,2FFT延长。200毫克剂量时达到最大效应,平均2FFT与平均血浆阿替洛尔浓度相关。所有剂量给药后2至5小时,SRT延长。100、200和400毫克剂量给药后2小时,DCT和SDMT的复测增益均低于服用安慰剂后。服用活性药物未改变完成GSMT所需的时间,但100和200毫克剂量给药后2小时错误数量减少。自我评定情绪量表显示,400毫克给药后2小时主观紧张感降低。结果表明,阿替洛尔在人体中发挥中枢效应。