Flumazenil discrimination by humans under a two-response and a novel-response procedure

作     者：Smith, BJ Bickel, WK 

作者机构：Univ Vermont Dept Psychiat Burlington VT USA Univ Vermont Dept Psychol Burlington VT 05405 USA 

出 版 物：《JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS》 (药理学与实验治疗学杂志)

年 卷 期：1999年第291卷第3期

页      面：1257-1268页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 100602[医学-中西医结合临床] 10[医学] 

基　　金：NIDA NIH HHS [R01 DA06205] Funding Source: Medline 

主　　题：咖啡因/药理学 中枢神经系统刺激剂/药理学 辨别(心理学)/药物作用 剂量效应关系 药物 氟马西尼/药理学 GABA调节剂/药理学 咪达唑仑/药理学 精神运动性行为/药物作用 三唑仑/药理学 青少年 成年人 女(雌)性 人类 男(雄)性 

摘      要：In this study we assessed the discriminative stimulus, self-reported, and performance effects of flumazenil in humans. The first group (n = 6) was trained to discriminate flumazenil (0.56 mg/70 kg i.v.) from saline and tested with flumazenil (0.10, 0.32, 0.56, and 1.0 mg/70 kg) under a two-response drug discrimination procedure. The second group (n = 8) was trained to discriminate flumazenil (0.56 mg/70 kg i.v.) from saline and tested with flumazenil (0.32, 0.56, and 1.0 mg/70 kg), midazolam (0.10, 0.56, and 1.0 mg/70 kg), and caffeine (75 mg/70 kg) under a novel-response drug discrimination procedure. In both groups, flumazenil was acquired and maintained as a discriminative stimulus. Flumazenil dose-dependently increased flumazenil-appropriate responding and ratings of strength of drug effect and sedation, and decreased ratings of stimulant effects and psychomotor performance. Under the novel-response procedure, midazolam produced dose-dependent increases in flumazenil-appropriate responding. However, midazolam produced 43 and 25% novel responding at the intermediate and highest test doses, respectively. Midazolam dose-dependently increased ratings of strength of drug effect and sedation, and decreased ratings of stimulant effects and psychomotor performance. The magnitude of effects on ratings of strength of drug effect and sedation were comparable after flumazenil and midazolam, but psychomotor performance effects were greater after midazolam than after flumazenil. Caffeine produced mostly saline-appropriate responding. The results indicate that flumazenil has agonist effects similar to those of midazolam;however, novel responding after midazolam, and the greater performance decrement after midazolam, suggest that flumazenil does not act as a traditional benzodiazepine agonist.