Noradrenergic Function and the Mechanism of Action of Antianxiety Treatment: I. The Effect of Long-term Alprazolam Treatment

doi:10.1001/archpsyc.1985.01790280040004

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Vol. 42 No. 5, May 1985

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Noradrenergic Function and the Mechanism of Action of Antianxiety Treatment

I. The Effect of Long-term Alprazolam Treatment

Dennis S. Charney, MD; George R. Heninger, MD

Arch Gen Psychiatry. 1985;42(5):458-467.

Abstract

• There Is preclinical and clinical evidence suggestingthat one neural mechanism responsible for antipanic efficacyis a reduction in brain noradrenergic function. Alprazolam,a triazolobenzodiazepine, has been demonstrated to have antipanicproperties; however, to our knowledge, its effects on noradrenergicfunction have not been established. To assess whether alprazolamalters noradrenergic function, the effects of alprazolam onbaseline plasma free 3-methoxy-4-hydroxyphenylethyleneglycol(MHPG), and yohimbine-induced increases In plasma MHPG level,anxiety-nervousness, blood pressure, and somatic symptoms werestudied in 14 patients with agoraphobia and panic disorder.Long-term alprazolam treatment significantly reduced plasmaMHPG baseline and blunted the yohimbine-induced increases inplasma MHPG, anxiety-nervousness, and sitting systolic bloodpressure. These observations suggest that the antipanic mechanismof action of alprazolam may be due in part to an interactionbetween benzodiazepine-sensitive and noradrenergic neural systems.

Author Affiliations

From the Clinical Research Unit, Ribicoff Research Facilities, Connecticut Mental Health Center, Department of Psychiatry, Yale University School of Medicine, New Haven.

Footnotes

Accepted for publication Oct 5, 1984.

Reprint requests to Connecticut Mental Health Center, 34 ParkSt, New Haven, CT 06508 (Dr Charney).

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