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  • The International Journal of Neuropsychopharmacology, Volume 10, Issue 1
  • February 2007, pp. 41-50

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

  • Pierre Blier (a1) (a2), Élise Saint-André (a1), Chantal Hébert (a1) (a2), Claude de Montigny (a1), Normand Lavoie (a3) and Guy Debonnel (a1)
  • DOI: http://dx.doi.org/10.1017/S1461145705006395
  • Published online: 01 May 2006
Abstract

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.

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Corresponding author
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: pblier@rohcg.on.ca
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The The International Journal of Neuropsychopharmacology
  • ISSN: 1461-1457
  • EISSN: 1469-5111
  • URL: /core/journals/the-international-journal-of-neuropsychopharmacology
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