Abstract
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.
Footnotes
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Send reprint requests to: Brandi J. Smith, Ph.D., Department of Psychiatry and Behavioral Science, Behavioral Biology Research Center, 5510 Nathan Shock Dr., Suite 3000, Baltimore, MD 21224. E-mail: brandi{at}welchlink.welch.jhu.edu
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↵1 This work was supported by United States Public Service Research Grant RO1 DA06205.
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↵2 Present address: Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, 5510 Nathan Shock Dr., Suite 3000, Baltimore, MD 21224-6823.
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Received for publication May 19, 1999.
- Abbreviations:
- ARCI
- Addiction Research Center Inventory
- FI
- fixed-interval
- VAS
- visual analog scale(s)
- PCAG
- pentobarbital-chlorpromazine-alcohol group scale
- MBG
- morphine-benzedrine
- LSD
- lysergic acid diethylamide
- BG
- benzedrine group scale
- A
- amphetamine
- DSST
- Digit Symbol Substitution Task
- Accepted August 19, 1999.
- The American Society for Pharmacology and Experimental Therapeutics
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