Influence of St John's wort on catecholamine turnover and cardiovascular regulation in humans.
BACKGROUND
St John's wort (Hypericum perforatum) is a popular over-the-counter antidepressant. Its antidepressive effect has been attributed in part to inhibition of monoamine transporters and monoamine oxidase, on the basis of in vitro studies.


METHODS
In a double-blind, randomized, placebo-controlled, crossover study, 16 healthy subjects (11 men and 5 women; mean age, 31 +/- 5 years) ingested either St John's wort (300 mg three times daily) or placebo for 7 days. Imipramine treatment (50 mg three times daily) in 7 subjects served as a positive control. After treatment, physiologic and biochemical tests included cardiovascular reflex testing, graded head-up tilt testing, and plasma catecholamine determinations.


RESULTS
St John's wort had no effect on blood pressure, heart rate, heart rate variability, or blood pressure variability, regardless of the test condition. St John's wort had no effect on plasma concentrations of norepinephrine and its main metabolite, dihydroxyphenylglycol, whereas plasma dihydroxyphenylacetic acid (DOPAC; the main metabolite of dopamine) concentrations increased in every subject (1661 +/- 924 pg/mL versus 1110 +/- 322 pg/mL with placebo, P=.04). In contrast, imipramine increased resting blood pressure (124 +/- 10 mmHg/71 +/- 5 mmHg versus 110 +/- 8 mmHg/61 +/- 6 mmHg with placebo, P=.005 for systolic values and P=.003 for diastolic values) and heart rate (74 +/- 7 beats/min versus 62 +/- 6 beats/min with placebo, P=.005) and elicited a marked orthostatic tachycardia (increase in heart rate of 43 +/- 17 beats/min versus 26 +/- 8 beats/min with placebo, P=.006).


CONCLUSIONS
Our findings challenge the concept that St John's wort elicits a major change in norepinephrine uptake or monoamine oxidase activity in vivo. The consistent increase in plasma DOPAC concentrations might suggest a novel mode of action or an inhibitory effect on dopamine beta-hydroxylase that should be followed up. We propose that a combination of physiologic and biochemical profiling may help better define the mode of action and potential side effects of herbal remedies.
Schroeder
Christoph
C
Franz Volhard Clinical Research Center, Charité-Campus Buch and Helio Klinikum, Berlin, Germany.
Tank
Jens
J
Goldstein
David S
DS
Stoeter
Michael
M
Haertter
Sebastian
S
Luft
Friedrich C
FC
Jordan
Jens
J
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000328:Adult; D000873:Anthracenes; D001341:Autonomic Nervous System / Q000187:drug effects; D002320:Cardiovascular Physiological Phenomena / Q000187:drug effects*; D002395:Catecholamines / Q000097:blood / Q000378:metabolism*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D020902:Hypericum; D007099:Imipramine / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives* / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D010569:Perylene / Q000031:analogs & derivatives* / Q000097:blood; D011187:Posture / Q000502:physiology; D016683:Supine Position / Q000502:physiology
D018759:Adrenergic Uptake Inhibitors; D000873:Anthracenes; D002395:Catecholamines; D020030:Nitric Oxide Donors; D015102:3,4-Dihydroxyphenylacetic Acid; D009599:Nitroprusside; D008734:Methoxyhydroxyphenylglycol; D010569:Perylene; C004965:hypericin; D007099:Imipramine; C010117:3,4-dihydroxyphenylglycol; D009638:Norepinephrine