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Sustained administration of the antidepressant venlafaxine in rats: pharmacokinetic and pharmacodynamic findings
- Source :
- Naunyn-Schmiedeberg's Archives of Pharmacology. 363:448-455
- Publication Year :
- 2001
- Publisher :
- Springer Science and Business Media LLC, 2001.
-
Abstract
- Rats were administered venlafaxine (10 mg/kg per day) for 14 days by using subcutaneously implanted osmotic minipumps. The present study assessed the distribution of VEN in different compartments, whether the VEN concentration in the compartments correlated, the effect of VEN on dialysate monoamine levels and on the spontaneous open-field behavior, and possible relations between the pharmacokinetic and pharmacodynamic parameters. The venlafaxine level in serum after sustained treatment was about 25% of the concentration in brain parenchyma and much higher than in brain dialysate. There was a clear correlation between venlafaxine concentrations in blood and brain compartments. The sustained venlafaxine challenge resulted in higher neocortical concentration of serotonin and noradrenaline, lower 5-hydroxyindole-3-acetic acid levels and increased locomotor activity in the central part of the test arena as compared to controls. No correlations were found between the venlafaxine concentration and brain monoamine parameters or the open-field behaviors. We conclude that, although species differences in pharmacokinetic properties for venlafaxine between rat and man exist, the pharmacokinetic correlations found after sustained treatment add information to the in vivo nature of the drug. Also, more studies like the present need to be performed to find the pharmacokinetic/pharmacodynamic interrelations for drugs like VEN.
- Subjects :
- Male
medicine.medical_specialty
Microdialysis
Venlafaxine
Pharmacology
Rats, Sprague-Dawley
Pharmacokinetics
medicine
Animals
Distribution (pharmacology)
Biogenic Monoamines
Tissue Distribution
Psychiatry
Behavior, Animal
business.industry
Body Weight
Venlafaxine Hydrochloride
General Medicine
Cyclohexanols
Rats
Monoamine neurotransmitter
Pharmacodynamics
Ven
Antidepressive Agents, Second-Generation
Antidepressant
Serotonin
business
medicine.drug
Subjects
Details
- ISSN :
- 14321912 and 00281298
- Volume :
- 363
- Database :
- OpenAIRE
- Journal :
- Naunyn-Schmiedeberg's Archives of Pharmacology
- Accession number :
- edsair.doi.dedup.....bd54478160b4d3d0fe2ab48e4b5d0115