Research article summary (published Apr 2000):

The role of 5-HT(1A) and 5-HT(1B/1D) receptors on the modulation of acute fluoxetine-induced changes in extracellular 5-HT: the mechanism of action of (+/-)pindolol.

Full Abstract

Some clinical evidence has suggested that (+/-)pindolol can be effective at producing a shortened time to onset of antidepressant activity when co-administered with a serotonin specific reuptake inhibitor (SSRI). This effect has been attributed to the antagonist effects of pindolol at the 5-HT(1A) receptor. In the present study, we compared the pharmacology of (+/-)pindolol, WAY-100635 (a 5-HT(1A) antagonist), GR127935 (a 5-HT(1B/1D) antagonist), and isamoltane (a 5-HT(1B) antagonist), when given acutely in combination with fluoxetine, using in vivo microdialysis in the frontal cortex of the freely moving rat. We have determined that the acute fluoxetine-induced increases in extracellular 5-HT can be augmented by (+/-)pindolol, WAY100635, GR127935 and isamoltane with maximum increases of 216+/-32%, 235+/-49%, 240+/-18% and 171+/-47% of preinjection control levels, respectively. Combination of both 5-HT(1A) and 5-HT(1B/1D) autoreceptor antagonists with fluoxetine produced additive increases in extracellular 5-HT (i.e. WAY100635+GR127935+fluoxetine and WAY100635+isamoltane+fluoxetine produced a four- and five-fold potentiation, respectively), suggesting that this strategy may be useful in further augmenting the action of a SSRI in the treatment of depression. In addition, by comparing the combined administration of (+/-)pindolol with either WAY100635, GR127935 or isamoltane, we have determined that (+/-)pindolol produces much of its acute potentiation of fluoxetine-induced increases in extracellular 5-HT via its action at the 5-HT(1B/D) receptor in addition to any activity it has at the presynaptic 5-HT(1A) receptor.

Author information

Author/s: Dawson, L A (LA); Nguyen, H Q (HQ);

Affiliation: CNS Disorders Division, Wyeth-Ayerst Research, Princeton, NJ 08543-8000, USA. dawson1(-atsign-)war.wyeth.com

Journal and publication information

Publication Type: Journal Article

Journal: Neuropharmacology (Neuropharmacology), published in ENGLAND. (Language: eng)

Reference: 2000-Apr; vol 39 (issue 6) : pp 1044-52

Dates: Created 2000/05/25; Completed 2000/05/25; Revised 2003/11/14;

PMID: 10727715, 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)

This article was linked to the MeSH Headings (categories) shown below.

Animals Autoreceptors - physiology Drug Synergism Extracellular Space - metabolism Fluoxetine - pharmacology Male Microdialysis Oxadiazoles - pharmacology Pindolol - pharmacology Piperazines - pharmacology Propanolamines - pharmacology

Propanolamines - pharmacology Pyridines - pharmacology Rats Rats, Sprague-Dawley Receptor, Serotonin, 5-HT1B Receptor, Serotonin, 5-HT1D Receptors, Serotonin - physiology Receptors, Serotonin, 5-HT1 Serotonin - metabolism Serotonin Antagonists - pharmacology Serotonin Uptake Inhibitors - pharmacology

Note: Bold headings indicate primary MeSH headings or qualifiers.

Associated Chemicals: Autoreceptors (0) ; Oxadiazoles (0) ; Piperazines (0) ; Propanolamines (0) ; Pyridines (0) ; Receptor, Serotonin, 5-HT1B (0) ; Receptor, Serotonin, 5-HT1D (0) ; Receptors, Serotonin (0) ; Receptors, Serotonin, 5-HT1 (0) ; Serotonin Antagonists (0) ; Serotonin Uptake Inhibitors (0) ; Pindolol (13523-86-9) ; WAY 100635 (146714-97-8) ; GR 127935 (148672-13-3) ; Serotonin (50-67-9) ; Fluoxetine (54910-89-3) ; isamoltane (99740-06-4)

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