The International Journal of Neuropsychopharmacology

Effects of different doses of venlafaxine on serotonin and norepinephrine reuptake in healthy volunteers

Pierre Blier a1a3c1, Élise Saint-André a1, Chantal Hébert a1a3, Claude de Montigny a1, Normand Lavoie a2 and Guy Debonnel a1
a1 Department of Psychiatry, McGill University, Montréal, QC, Canada
a2 Department of Urology, McGill University, Montréal, QC, Canada
a3 University of Ottawa Institute of Mental Health Research, Ottawa, ON, Canada

Article author query
blier p   [PubMed][Google Scholar] 
saint-andre e   [PubMed][Google Scholar] 
hebert c   [PubMed][Google Scholar] 
de montigny c   [PubMed][Google Scholar] 
lavoie n   [PubMed][Google Scholar] 
debonnel g   [PubMed][Google Scholar] 


Venlafaxine is generally considered to be a dual 5-HT and NE reuptake inhibitor when it is used at doses above 75 mg/d in humans. While its 5-HT reuptake-inhibiting property has been demonstrated, some controversy still exists regarding the doses of venlafaxine required to inhibit NE reuptake. Healthy male volunteers received, on a double-blind basis, paroxetine (20 mg/d), desipramine (100 mg/d), nefazodone (300 mg/d), or venlafaxine (150 or 300 mg/d) in the last 5 d of a 7-d period of administration. Inhibition of 5-HT reuptake was estimated by determining the degree of depletion of whole-blood 5-HT, while that of NE was assessed by measuring the attenuation of the systolic blood pressure increases produced by intravenous injections of tyramine. Paroxetine, both regimens of venlafaxine, and to a lesser extent desipramine significantly decreased whole-blood 5-HT content. Nefazodone failed to produce any significant change. Desipramine abolished the tyramine pressor response, whereas all other drug regimens left this parameter unaltered. Venlafaxine and paroxetine acted as potent 5-HT reuptake inhibitors in the present study. In contrast, neither the moderate nor the high dose of venlafaxine displayed any significant inhibiting activity in this model assessing NE reuptake in peripheral NE terminals. The validity of the model was confirmed by the potent inhibitory action of desipramine on NE reuptake. While the reasons for this unexpected lack of action remain unclear, venlafaxine appeared to be an effective NE reuptake agent in depressed patients using the same approach.

(Received September 13 2005)
(Reviewed October 30 2005)
(Revised November 14 2005)
(Accepted November 22 2005)
(Published Online May 11 2006)

Key Words: Antidepressant; nefazodone; paroxetine; reuptake inhibition; tyramine.

c1 University of Ottawa Institute of Mental Health Research, Royal Ottawa Hospital, Lady Grey Building, Suite 2043, Ottawa, Ontario, Canada K1Z 7K4. Tel.: 613-722-6521 (ext. 6908) Fax: 613-761-3610 E-mail: