Oral yohimbine in human autonomic failure

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Abstract
Yohimbine is an α2-adrenoreceptor antagonist that acts to enhance sympathetic nervous system discharge and potentiate sympathetically mediated cardiovascular reflex responses. We therefore assessed the ability of yohimbine to increase sympathoadrenal discharge and raise blood pressure (BP) in patients with autonomic failure characterized by profound orthostatic hypotension. Yohimbine 5 mg orally in eight seated patients significantly elevated mean systolic BP by 33 mm Hg from 136 ± 15 (mean ± SD) to a maximum of 169 ± 23 mm Hg (p < 0.01), mean diastolic BP by 16 mm Hg from 77 ± 9 to a maximum of 93 ± 15 mm Hg (p < 0.01), and mean heart rate (HR) by 10 beats per minute (BPM) from 68 ± 12 to a maximum of 781 17 BPM (p < 0.01). Plasma norepinephrine (NE) increased from 104 ± 71 to a maximum of 196 ± 182pg/ml(p < 0.05), but plasma epinephrine (E) did not increase significantly (31 ± 18 versus a maximum of 39 ± 21 pg/ml). In five patients given yohimbine 2.5 mg orally, BP, HR, NE, and E tended to increase, but the changes were not significant. Plasma yohimbine levels correlated significantly with the changes in mean arterial pressure (r = 0.61, p < 0.01). Yohimbine raises BP and HR in patients with autonomic failure. These effects are dose- and concentration-dependent and mediated through increased sympathetic discharge. Yohimbine may be useful in the treatment of orthostatic hypotension associated with autonomic failure. It is unique among current modes of therapy for this disorder in that it enhances discharge of the patient's own sympathetic system.