Dose-dependent influence of buspirone on the activities of selective serotonin reuptake inhibitors in the mouse forced swimming test. Analysis of cis-trans isomers and enantiomers of sertraline by cyclodextrin-modified micellar electrokinetic chromatography. Economic consequences of selective serotonin reuptake inhibitor use with drugs also metabolized by the cytochrome P-450 system. Rx drugs

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Psychopharmacology (Berl). 1998 Jul;138(2):198-206.
Dose-dependent influence of buspirone on the activities of selective serotonin reuptake inhibitors in the mouse forced swimming test.

Redrobe JP, Bourin M.

GIS Medicament, JE 2027 Neurobiologie de l'Anxiete, Faculte de Medecine, Nantes, France.

Recent clinical data suggest that buspirone may enhance the efficacy and/or reduce the latency to therapeutic effect of selective serotonin reuptake inhibitors (SSRIs) in unipolar major depressive disorder. The present study, using the mouse forced swimming test, was performed to investigate further the mechanisms involved in the potential antidepressant-enhancing effects of buspirone. Prior administration of buspirone (0.06 mg kg(-1), i.p.) significantly enhanced the anti-immobility effects of subactive doses of fluvoxamine (4 mg kg(-1), i.p.; P < 0.01), paroxetine (4 mg kg(-1), i.p.; P < 0.01), citalopram (4 mg kg(-1), i.p.; P < 0.01) and sertraline (2 mg kg(-1), i.p.; P < 0.01) in the forced swimming test. However, pretreatment with buspirone did not induce antidepressant-like effects when tested in combination with fluoxetine (4 mg kg(-1), i.p.). Each antidepressant tested reduced immobility time in the forced swimming test [citalopram (16 mg kg(-1), i.p.; P < 0.01), fluoxetine (32 mg kg(-1), i.p.; P < 0.01), fluvoxamine (32 mg kg(-1), i.p.; P < 0.01), paroxetine (16 mg kg(-1), i.p.; P < 0.01) and sertraline (16 mg kg(-1), i.p.; P < 0.01)]. Pretreatment with buspirone (0.5 mg kg(-1), i.p.), or its major metabolite 1-PP (0.5 mg kg(-1), i.p.), attenuated all SSRI-induced anti-immobility effects (P < 0.01). Concomitant studies of locomotor activity ruled out any stimulant or sedative effects of the interactions. The results of the present study suggested that low dose buspirone enhanced the activity of subactive doses of SSRIs in the mouse forced swimming test, probably via an action at 5-HT1A receptors. On the other hand, a high dose of buspirone attenuated the antidepressant-like effects of active doses of these drugs, possibly via the generation of an active metabolite (1-PP) acting at alpha2-adrenoreceptors.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9718290&dopt=Abstract

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J Chromatogr A. 2000 Feb 25;871(1-2):207-15.
Analysis of cis-trans isomers and enantiomers of sertraline by cyclodextrin-modified micellar electrokinetic chromatography.

Lucangioli SE, Hermida LG, Tripodi VP, Rodriguez VP, Lopez EE, Rouge PD, Carducci CN.

Faculty of Pharmacy and Biochemistry, Department of Analytical Chemistry and Physicochemistry, University of Buenos Aires, Junin, Argentina.

In this work development, optimization and validation of a cyclodextrin-modified micellar electrokinetic chromatography (CD-modified MEKC) method is proposed to resolve separation of the sertraline hydrochloride and synthesis-related substances. Sertraline hydrochloride, the cis-(1S,4S) enantiomer form, is used as an antidepressant therapeutic agent. A buffer concentration composed of 20 mM sodium borate, pH 9.0 with 50 mM sodium cholate, 15 mM sulfated beta-cyclodextrin and 5 mM hydroxypropyl-beta-cyclodextrin was found to be the most suitable background electrolyte. Quantitation of the impurities at levels of 0.1% in different samples of the bulk drug was determined. A comparison of the results with those obtained by HPLC methodology was also accomplished. The method proved appropriate for testing the purity of sertraline hydrochloride in bulk drug.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10735301&dopt=Abstract

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Clin Ther. 1998 Jul-Aug;20(4):780-96.
Economic consequences of selective serotonin reuptake inhibitor use with drugs also metabolized by the cytochrome P-450 system.

Ozminkowski RJ, Hylan TR, Melfi CA, Meneades LM, Crown WH, Croghan TW, Robinson RL.

The MEDSTAT Group, Inc., Ann Arbor, Michigan, USA.

Administration of selective serotonin reuptake inhibitors (SSRIs) may increase plasma concentrations of concomitant medications that are also metabolized by the cytochrome P-450 system (CYP-450), in particular by the 2D6 and 3A4 isoenzymes. This may lead to side effects or other clinical events that might be expected to incur higher health-care expenditures. The purpose of this study was to assess whether there was a difference in expenditures during the first 90 days of SSRI therapy with paroxetine or sertraline versus fluoxetine in patients who were also receiving a stable dosage of a nonpsychiatric drug also metabolized by the CYP-450 2D6 or 3A4 isoenzyme systems. A sample of 2445 patients who initiated therapy with an SSRI while receiving a stable dosage of a nonpsychiatric drug was obtained from a private insurance claims database. Multivariate regression techniques were used to estimate total health-care expenditures in the first 90 days after receiving a prescription for an SSRI. After adjusting for nonrandom SSRI prescription patterns and controlling for observable and unobservable characteristics that might correlate with SSRI selection, total health-care expenditures were 95% higher for patients initiating SSRI therapy with sertraline or paroxetine compared with fluoxetine. Results suggest that there are cost differences between SSRIs during concomitant therapy with drugs also metabolized by the CYP-450 system. To determine whether there are additional differences in expenditures across SSRIs, future research should focus on (1) simultaneous initiation of SSRI therapy and a nonpsychiatric drug also metabolized by the CYP-450 enzyme system, and (2) addition of nonpsychiatric drug therapy to stable SSRI therapy. Relationships between additional expenditures, drug interactions, and clinical outcomes should also be assessed directly using medical records and patient interview data that are not available in claims-based files.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9737837&dopt=Abstract

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