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Blockade of 5-hydroxytryptamine and noradrenaline uptake by venlafaxine: a comparative study with paroxetine and desipramine.
Full Abstract
1. Venlafaxine is an antidepressant agent which blocks in vitro the reuptake of both 5-HT and NA. The present in vivo electrophysiological studies were undertaken, in the rat, to compare the effects of venlafaxine on 5-HT and NA reuptake to those of the selective 5-HT reuptake inhibitor paroxetine and the selective NA reuptake inhibitor desipramine. 2. Administered acutely, venlafaxine dose-dependently prolonged the time required for a 50% recovery (RT50) of the firing activity of dorsal hippocampus CA3 pyramidal neurons from the suppression induced by microiontophoretic applications of 5-HT and NA. Venlafaxine and paroxetine increased with a similar potency the RT50 values for 5-HT, while desipramine was more potent than venlafaxine at increasing the RT50 values for NA. Moreover, venlafaxine demonstrated a greater potency at increasing the RT50 values for 5-HT compared to that of NA. 3. A two-day treatment with venlafaxine (delivered s.c. by osmotic minipumps) increased the RT50 values for both 5-HT and NA applications. The RT50 values for 5-HT were significantly increased at a dose of 10 mg kg(-1) day(-1), whereas those for NA were increased at a dose of 20 mg kg(-1) day(-1), consistent with the data obtained following the acute administration of venlafaxine. 4. Taken together, these results indicate that, in vivo, venlafaxine blocks both reuptake processes, with a potency greater for the 5-HT than for the NA reuptake process. This dual action, combined with the differential potency of venlafaxine, might constitute the biological substratum responsible for its apparent unique clinical efficacy in major depression.
Author information
Author/s: Béïque, J C (JC); de Montigny, C (C); Blier, P (P); Debonnel, G (G);
Affiliation: Neurobiological Psychiatry Unit, McGill University, Montréal, Canada.
Journal and publication information
Publication Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't
Journal: British journal of pharmacology (Br J Pharmacol), published in ENGLAND. (Language: eng)
Reference: 1998-Oct; vol 125 (issue 3) : pp 526-32
Dates: Created 1999/03/04; Completed 1999/03/04; Revised 2008/11/20;
PMID: 9806336, status: MEDLINE (last retrieved date: 2/18/2009)
Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.
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MeSH headings (categories)
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Associated Chemicals: Adrenergic Uptake Inhibitors (0) ; Cyclohexanols (0) ; Serotonin Uptake Inhibitors (0) ; Desipramine (50-47-5) ; Serotonin (50-67-9) ; Norepinephrine (51-41-2) ; Paroxetine (61869-08-7) ; venlafaxine (93413-69-5)Related articles
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