Noradrenergic function and the mechanism of action of antianxiety treatment. I. The effect of long-term alprazolam treatment.

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.