Comparison of the effects of venlafaxine, desipramine, and paroxetine on noradrenaline- and methoxamine-evoked constriction of the dorsal hand vein.
OBJECTIVE
To examine whether the antidepressant venlafaxine, a novel serotonin-noradrenaline re-uptake inhibitor (SNRI), can modify alpha-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 microg 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.
Abdelmawla
A H
AH
Department of Psychiatry, Queen's Medical Centre, Nottingham NG7 2UH, UK.
Langley
R W
RW
Szabadi
E
E
Bradshaw
C M
CM
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D003511:Cyclohexanols / Q000494:pharmacology*; D003891:Desipramine / Q000494:pharmacology; D004311:Double-Blind Method; D004347:Drug Interactions; D006225:Hand / Q000098:blood supply; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D017374:Paroxetine / Q000494:pharmacology; D012472:Salivation / Q000187:drug effects; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*; D014680:Veins / Q000187:drug effects* / Q000502:physiology; D000069470:Venlafaxine Hydrochloride
D000316:Adrenergic alpha-Agonists; D003511:Cyclohexanols; D003891:Desipramine; D008729:Methoxamine; D009638:Norepinephrine; D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors; D000069470:Venlafaxine Hydrochloride