Comparison of the effects of venlafaxine, desipramine, and paroxetine on noradrenaline‐ and methoxamine‐evoked constriction of the dorsal hand vein

• Published in: British journal of clinical pharmacology Vol. 48; no. 3; pp. 345 - 354
• Main Authors: ABDELMAWLA, A. H, LANGLEY, R. W, SZABADI, E, BRADSHAW, C. M
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01-09-1999; Blackwell Science; Blackwell Science Inc
• Subjects: Adrenergic alpha-Agonists - pharmacology; Adult; Biological and medical sciences; Blood Pressure - drug effects; Cross-Over Studies; Cyclohexanols - pharmacology; desipramine; Desipramine - pharmacology; dorsal hand vein; Double-Blind Method; Drug Interactions; Hand - blood supply; Heart Rate - drug effects; Humans; Male; Medical sciences; Methoxamine - pharmacology; Neuropharmacology; Norepinephrine - pharmacology; Original; paroxetine; Paroxetine - pharmacology; Pharmacology. Drug treatments; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Salivation - drug effects; Serotonin Uptake Inhibitors - pharmacology; Vasoconstriction - drug effects; Veins - drug effects; Veins - physiology; venlafaxine; Venlafaxine Hydrochloride; α1‐adrenoceptors; Desipramine; Psychotropic; α1-Adrenergic receptor; Reuptake inhibitor; Dose activity relation; Piperidine derivatives; Antidepressant agent; Clinical trial; Venlafaxine; Drug interaction; Methoxamine; Human; Paroxetine; Drug combination; Healthy subject; Serotonin; Vasoconstriction; Oral administration; Tricyclic compound; Hand; Norepinephrine; Circulatory system; Hemodynamics; Saliva; Comparative study
• ISSN: 0306-5251; 1365-2125
• DOI: 10.1046/j.1365-2125.1999.00031.x

Aims To examine whether the antidepressant venlafaxine, a novel serotonin‐noradrenaline re‐uptake inhibitor (SNRI), can modify α‐adrenoceptor‐mediated venoconstriction in man. The effects of venlafaxine were compared with those of desipramine, a tricyclic antidepressant with noradrenaline uptake inhibiting properties, and paroxetine, a selective serotonin re‐uptake inhibitor (SSRI), on noradrenaline‐and methoxamine‐evoked venoconstriction using the dorsal hand vein compliance technique.
Methods Fifteen healthy male volunteers participated in five weekly experimental sessions. Each session was associated with a clinically effective dose of an antidepressant or placebo. The following oral dosages were used: venlafaxine 75 mg, venlafaxine 150 mg, desipramine 100 mg, paroxetine 20 mg, or placebo. A double‐blind, cross‐over, balanced design was used. In each session, dose–response curves to both locally infused noradrenaline acid tartrate (0.1–33.33 ng min−1 ) and methoxamine hydrochloride (0.5–121.5 μg min−1 ) were constructed. Systolic and diastolic blood pressure and pulse rate were measured in the supine and erect positions. Salivation was measured by the dental roll technique.
Results Venlafaxine 150 mg and desipramine 100 mg potentiated the venoconstrictor response to noradrenaline (anova of log ED50s: P<0.01; individual comparisons: venlafaxine 150 mg vs placebo: P<0.005; mean difference, 95% CI: −0.49 (−0.81, −0.17); desipramine 100 mg vs placebo: P<0.005; mean difference, 95% CI: −0.34 (−0.60, −0.09) without affecting the response to methoxamine. Neither paroxetine nor placebo had any effects on the venoconstrictor responses. Both doses of venlafaxine increased systolic blood pressure (supine and erect) and venlafaxine 150 mg increased diastolic blood pressure (supine) (anova, P<0.05). Desipramine increased heart rate (P<0.05). Desipramine and both doses of venlafaxine reduced salivation (P<0.025).
Conclusions These results show that, similarly to desipramine 100 mg, venlafaxine 150 mg can potentiate venoconstrictor responses to noradrenaline, consistent with venlafaxine’s ability to block noradrenaline uptake in man. The importance of noradrenaline uptake blockade in these observations is confirmed by the lack of effect of the antidepressants on methoxamine‐evoked venoconstriction and the failure of paroxetine to modify noradrenaline‐evoked venoconstriction.