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Neurochemical, pharmacokinetic, and behavioral effects of the novel selective serotonin reuptake inhibitor BMS-505130
- Source :
-
Pharmacology, Biochemistry & Behavior . Mar2005, Vol. 80 Issue 3, p521-528. 8p. - Publication Year :
- 2005
-
Abstract
- Abstract: BMS-505130 is a potent and selective serotonin transport inhibitor; K i for binding to the serotonin transporter=0.18 nM (K i values for binding to the norepinephrine and dopamine transporters=4.6 and 2.1 μM, respectively). In platelet serotonin uptake studies BMS-505130 (5 mg/kg, p.o.) produced a robust inhibition of serotonin uptake. In microdialysis studies oral dosing with BMS-505130 produced a dose-dependent increase in cortical serotonin levels that reached a maximal effect of 200% above baseline at a dose of 1 mg/kg, p.o.; the peak serotonin response was transient in nature. Following oral administration, peak plasma concentrations of BMS-505130 reached Tmax at 1.6±0.7 h and then declined to concentrations <10% of Cmax within the following 6 h; plasma half-life following i.v. dosing was 0.46±0.02 h. Parallel microdialysis and pharmacokinetic studies revealed that changes in serotonin levels in the cortex mirrored changes in the brain concentration of BMS-505130. In a behavioral assay known to be sensitive to selective serotonin reuptake inhibitors (SSRIs), mouse tail suspension, BMS-505130 produced a robust response after either oral or intraperitoneal dosing. BMS-505130 exhibits a pharmacological, neurochemical and behavioral profile consistent with a potent SSRI. Moreover, BMS-505130''s short half-life may be advantageous for the treatment of premature ejaculation where an acute effect to delay ejaculation followed by a relatively rapid fall in SSRI plasma concentrations might be desirable. [Copyright &y& Elsevier]
- Subjects :
- *PREMATURE ejaculation
*SEROTONIN uptake inhibitors
*NEUROTRANSMITTERS
*SEROTONIN
Subjects
Details
- Language :
- English
- ISSN :
- 00913057
- Volume :
- 80
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- Pharmacology, Biochemistry & Behavior
- Publication Type :
- Academic Journal
- Accession number :
- 17435629
- Full Text :
- https://doi.org/10.1016/j.pbb.2005.01.007