Dissociation of norepinephrine turnover from alpha-2 responses after clorgiline

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Abstract
Responses to intravenous clonidine, a possible central noradrenergic probe, were examined in patients with depression before and after treatment with clorgiline, a selective monoamine oxidase type A inhibitor. Pulse rate, mean arterial blood pressure, plasma norepinephrine, 3‐methoxy‐4‐hydroxyphenylglycol, and growth hormone were measured. Clorgiline treatment (2.5 to 10 mg/day) produced a variable reduction in the hypotensive response to clonidine but did not influence heart rate or plasma norepinephrine responses. Clorgiline markedly reduced the urinary output of norepinephrine and metabolites, indicating a reduced turnover of norepinephrine. None of the measured parameters corresponded with clinical effect. These data suggest that any clorgiline‐induced alterations in α2‐receptor function as measured by responses to clonidine are modest and highly variable. Furthermore, since the variable and inconsistent changes in α2‐receptor function are dissociated from the massive changes in norepinephrine metabolism, regulation of presynaptic α2‐receptors appears unlikely to mediate the effects of clorgiline in patients with depression. Clinical Pharmacology and Therapeutics (1988) 43, 32–38; doi:10.1038/clpt.1988.8