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Anxiolytic-Like Effects of Escitalopram, Citalopram, and R-Citalopram in Maternally Separated Mouse Pups
The S -enantiomer of citalopram, escitalopram, is a selective serotonin reuptake inhibitor (SSRI) that appears to be responsible for citalopram's antidepressant and anxiolytic effects. Clinically, escitalopram is reported to have fewer adverse side effects than do other SSRIs. This study compar...
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Published in: | The Journal of pharmacology and experimental therapeutics 2004-02, Vol.308 (2), p.474-480 |
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Main Authors: | , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | The S -enantiomer of citalopram, escitalopram, is a selective serotonin reuptake inhibitor (SSRI) that appears to be responsible
for citalopram's antidepressant and anxiolytic effects. Clinically, escitalopram is reported to have fewer adverse side effects
than do other SSRIs. This study compared escitalopram to other antidepressants in a preclinical procedure predicting anxiolytic-like
effects of drugs. Carworth Farms Webster (CFW) mouse pups (7 days old) were separated from the dam and maintained at a temperature
of 34°C. Forty-five minutes after administering citalopram (0.56â10 mg/kg), escitalopram (0.0056â3 mg/kg), R -citalopram (1â10 mg/kg), paroxetine (0.3â3 mg/kg), fluoxetine (1â30 mg/kg), or venlafaxine (3â56 mg/kg) subcutaneously, the
pups were placed individually on a 19.5°C surface for 4 min. Ultrasonic vocalizations (USVs) (30â80 kHz), grid crossing, rolling
(i.e., the pup turned on one side or its back), and colonic temperature were recorded. All the drugs reduced USV emission;
escitalopram was the most potent (ED 50 0.05 mg/kg), followed by paroxetine (0.17 mg/kg), citalopram (1.2 mg/kg), fluoxetine (4.3 mg/kg), R -citalopram (6 mg/kg), and venlafaxine (7 mg/kg) . The doses that decreased USVs differed from those that increased motor activity. Increased grid crossing occurred after low
doses of paroxetine (0.03 or 0.1 mg/kg) and fluoxetine (1 mg/kg), but only after the highest doses of the citalopram enantiomers
and venlafaxine (0.3, 10, and 56 mg/kg, respectively). Except for escitalopram and venlafaxine, high doses of the treatments
increased rolling. R -Citalopram caused a 10-fold rightward shift in escitalopram's dose-effect curve, suggesting that R -citalopram inhibits escitalopram's anxiolytic-like effects. These data support clinical findings that escitalopram is a potent,
well tolerated SSRI with anxiolytic-like effects. |
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ISSN: | 0022-3565 1521-0103 |
DOI: | 10.1124/jpet.103.058206 |