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.
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D000328:Adult; D000379:Agoraphobia / Q000188:drug therapy / Q000378:metabolism; D000525:Alprazolam; D014151:Anti-Anxiety Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001008:Anxiety Disorders / Q000188:drug therapy* / Q000378:metabolism; D001569:Benzodiazepines / Q000494:pharmacology* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000097:blood; D008875:Middle Aged; D009638:Norepinephrine / Q000378:metabolism*; D010200:Panic / Q000187:drug effects; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects; D013997:Time Factors; D015016:Yohimbine / Q000494:pharmacology
D014151:Anti-Anxiety Agents; D011942:Receptors, Adrenergic, alpha; D011963:Receptors, GABA-A; D001569:Benzodiazepines; D015016:Yohimbine; D008734:Methoxyhydroxyphenylglycol; D009638:Norepinephrine; D000525:Alprazolam