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Intravenous alprazolam challenge in normal subjects

Biochemical, cardiovascular, and behavioral effects

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Abstract

Alprazolam, a novel benzodiazepine derivative is thought to be effective in the treatment of anxiety, panic, and depressive disorders. There is considerable interest in alprazolam's mechanism of action, particularly whether its profile of actions might resemble that of the α2 adrenore-ceptor agonist, clonidine. The present study assessed the biochemical, cardiovascular, and behavioral responses of healthy volunteers to acute intravenous infusions of alprazolam and placebo. Alprazolam reduced ACTH and cortisol while increasing growth hormone. There was a transient reduction in plasma norepinephrine and only modest effects on cardiovascular parameters. Subjects became quite sedated after intravenous alprazolam. This pharmacodynamic profile resembles that previously reported for traditional benzodiazepines, although alprazolam may be a more potent stimulator of growth hormone release. Alprazolam's effects on growth hormone resemble those of clonidine, but unlike clonidine, alprazolam has relatively little effect on plasma catecholamine and cardiovascular parameters. This suggests that α2 mechanisms do not play a primary role in alprazolam's mode of action. Since alprazolam infusion affects three different measures (ACTH/cortisol, growth hormone, and plasma norepinephrine) thought to be dysregulated in depression, challenge with intravenous alprazolam may prove to be a useful “probe” in affective disorders.

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Author notes

  1. Emile D. Risby

    Present address: Department of Psychiatry, Emory University School of Medicine, 30322, Atlanta, GA, USA

  2. Robert N. Golden

    Present address: Department of Psychiatry, University of North Carolina, School of Medicine, 27514, Chapel Hill, NC, USA

Authors and Affiliations

  1. Section of Clinical Pharmacology, Laboratory of Clinical Science, National Institute of Mental Health, Building 10, Room 2D46, 20892, Bethesda, MD, USA

    Emile D. Risby, John K. Hsiao, Robert N. Golden & William Z. Potter

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Risby, E.D., Hsiao, J.K., Golden, R.N. et al. Intravenous alprazolam challenge in normal subjects. Psychopharmacology 99, 508–514 (1989). https://doi.org/10.1007/BF00589900

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