May 1985

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

Author Affiliations

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

Arch Gen Psychiatry. 1985;42(5):458-467. doi:10.1001/archpsyc.1985.01790280040004

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