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October 1989

Idazoxan: A Selective α2-Antagonist and Effective Sustained Antidepressant in Two Bipolar Depressed Patients

Author Affiliations

Section on Clinical Pharmacology National Institute of Mental Health Bethesda, MD 20892

Arch Gen Psychiatry. 1989;46(10):958-959. doi:10.1001/archpsyc.1989.01810100100021

To the Editor.—  We report on the therapeutic and biochemical effects of short- and long-term administration of idazoxan, a selective α2-administration and a putative antidepressant, in three patients with the diagnosis of depression and a history of poor response to standard treatments. The down regulation of central β-receptors in response to increased synaptic norepinephrine (NE) levels has consistently been demonstrated after tricyclic antidepressant1 as well as other effective treatments for depression.2,3 In addition, α2-adrenergic receptors have been shown to down regulate in response to at least some antidepressants.4,5 Furthermore, blockade of α-receptors can accelerate the down regulation of β-receptors by tricyclic antidepressants in rats,6 probably by enhancing intrasynaptic NE through the blockade of prejunctional α2-receptors that normally mediate feedback inhibition of NE release.7 In human studies, however, the addition of yohimbine therapy to patients who had failed to respond

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