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The treatment of neurogenic orthostatic hypotension with 3,4-DL-threo-dihydroxyphenylserine

A randomized, placebo-controlled, crossover trial

From the Department of Neurology (Dr. Freeman), Beth Israel Deaconess Medical Center Harvard Medical School, Boston, MA; and the Department of Medicine (Drs. Landsberg and Young), Northwestern University Medical School, Northwestern University, Chicago, IL.

Address correspondence and reprint requests to Dr. Roy Freeman, Autonomic and Peripheral Nerve Laboratory, Department of Neurology, Beth Israel Deaconess Medical Center, 1 Deaconess Road, Boston, MA 02215.

OBJECTIVE: To study the therapeutic effect and mechanism of action of 3,4-DL-threo-dihydroxyphenylserine (DL-DOPS) in neurogenic orthostatic hypotension.

METHODS: The blood pressure (BP) response to an orthostatic challenge on DL-DOPS was compared with that of placebo in a randomized, double-blind, placebo-controlled, crossover trial in 10 patients. The mechanism of action of DOPS was studied by measuring forearm vascular resistance and changes in supine and upright plasma DL-DOPS and norepinephrine levels. The effect of DL-DOPS on the quality of life was determined by questionnaire.

RESULTS: DL-DOPS increased the supine (p < 0.001) and upright (p < 0.05) systolic blood pressure (SBP) and diastolic blood pressure (DBP) (both p < 0.01). The peak SBP on DL-DOPS in the supine position occurred 300 minutes after ingestion of the medication. The increase in BP was accompanied by an increase in plasma levels of norepinephrine and DL-DOPS in both the supine and upright positions after DL-DOPS ingestion (p < 0.0001). There was a trend toward improvement in symptoms of orthostatic intolerance.

CONCLUSION: DL-DOPS improved features of neurogenic orthostatic hypotension in patients with central and peripheral autonomic nervous system disease. There was an increase in plasma norepinephrine. No major side effects occurred.

Key words: Orthostatic hypotension—3—4-DL-threo-dihydroxyphenylserine—Autonomic failure.

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