sertraline, Zoloft
Sertraline pharmacokinetics and dynamics in adolescents.

Axelson DA, Perel JM, Birmaher B, Rudolph GR, Nuss S, Bridge J, Brent DA.

University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, PA 15213, USA. axelsonda msx.upmc.edu

OBJECTIVE: To determine the pharmacokinetics of sertraline in adolescents and assess its effect on a surrogate marker of serotonin transport. METHOD: Pharmacokinetic parameters of a single 50-mg dose of sertraline were determined in 10 adolescents. Steady-state withdrawal kinetics were determined in 12 adolescents taking 50 mg/day and in 6 adolescents taking 100 to 150 mg/day. Platelet serotonin reuptake was measured before and after 2 weeks of daily 50-mg dosing. RESULTS: The mean steady-state half-life of 50 mg was significantly shorter (15.3 +/- 3.5 hours) than the single-dose half-life (26.7 +/- 5.2 hours; t = 6.4, p < .001) and the steady-state half-life at 100 to 150 mg/day (20.4 +/- 3.4 hours; t = 2.9, p = .01). Platelet serotonin reuptake was inhibited by 61 +/- 15% after approximately 2 weeks of sertraline 50 mg/day. CONCLUSIONS: The half-life of sertraline 50 mg becomes significantly shorter from the initial dose to steady-state, and many adolescents may benefit from twice-per-day dosing. The steady-state half-life increases as the dose increases. The moderate levels of platelet reuptake inhibition at 50 mg/day indicate that most adolescents may need sertraline doses higher than 50 mg/day to attain a therapeutic response.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12218424&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
Sertraline in the treatment of minor depression in nursing home residents: a pilot study.

Rosen J, Mulsant BH, Pollock BG.

Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA 15241, USA.

'Minor' depression affects up to 50% of residents in long-term care facilities and is associated with considerable discomfort, disability and risk of morbidity. Despite the prevalence of this problem, few studies addressing the treatment of these patients have been conducted. In an open clinical trial, 12 nursing home residents who met the DSM-IV description for minor depressive disorder were treated with sertraline for 6 weeks. Adverse effects and clinical response were monitored. All residents tolerated their medication without any significant side-effects. At the completion of the study, the Hamilton Depression Rating Scale and Global Assessment Scale change scores both indicated significant improvement and 75% of the residents met criteria for 'remission'. This preliminary study provides evidence that nursing home residents with minor depression tolerated treatment with sertraline and improved clinically. Copyright 2000 John Wiley & Sons, Ltd.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10679849&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
Comparative study of fluoxetine, sibutramine, sertraline and dexfenfluramine on the morphology of serotonergic nerve terminals using serotonin immunohistochemistry.

Kalia M, O'Callaghan JP, Miller DB, Kramer M.

Department of Biochemistry, Molecular Pharmacology and Anesthesiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA. mkalia msn.com

We compared the effects of treatment with high doses of fluoxetine, sibutramine, sertraline, and dexfenfluramine for 4 days on brain serotonergic nerve terminals in rats. Methylenedioxymethamphetamine (MDMA) and 5,7-dihydroxytryptamine (5,7-DHT) were used as positive controls because both compounds deplete brain serotonin. Food intake and body weight changes were also monitored and yoked, pair-fed animals were used to control for possible changes in morphology due to nutritional deficits. Fluoxetine, sibutramine, sertraline and dexfenfluramine all produced a significant reduction in body weight. Fluoxetine, sibutramine and sertraline treatment resulted in no depletion of brain serotonin but produced morphological abnormalities in the serotonergic immunoreactive nerve network. In contrast, dexfenfluramine and MDMA depleted brain serotonin and produced morphological changes in the serotonin nerve network. These results indicate that even though fluoxetine, sibutramine and sertraline do not deplete brain serotonin, they do produce morphological changes in several brain regions (as identified by serotonin immunohistochemistry). Dexfenfluramine and MDMA, on the other hand, markedly deplete brain serotonin and also produce morphological changes. Collectively, these results lend support to the concept that all compounds acting on brain serotonin systems, whether capable of producing serotonin depletion or not, could produce similar effects on the morphology of cerebral serotonin systems.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10700602&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
Spectrophotometric determination of fluoxetine and sertraline using chloranil, 2, 3 dichloro-5, 6 dicyano benzoquinone and iodine.

Bebawy LI, El-Kousy N, Suddik JK, Shokry M.

National Organization for Drug Control and Research, Egypt.

Spectrophotometric procedures are presented for the determination of two commonly used antidepressant drugs, fluoxetine (I) and sertraline hydrochloride (II). The methods are based mainly on charge transfer complexation reaction of these drugs with either pi acceptors chloranil and 2, 3 dichloro-5, 6-dicyanoquinone (DDQ) or sigma acceptor iodine. The colored products are quantified spectrophotometrically at 550, 450 and 263 nm for fluoxetine and at 450, 455 and 290 nm for sertraline in chloranil, DDQ and iodine methods, respectively. The molar combining ratio and the optimum assay conditions were studied. The methods determine the cited drugs in concentration ranges of 8-640, 16-112 and 7.5-60 microg/ml with mean percentage recoveries of 99.83, 99.76 and 100.00% and R.S.D. of 1.24, 0.95 and 1.13% in fluoxetine and ranges of 16-160, 15-105 and 6-48 microg/ml with mean percentage recoveries of 100.39, 99.78 and 99.69% and R.S.D. of 1.02, 0.81 and 0.57% in sertraline for chloranil, DDQ and iodine methods, respectively. A more detailed investigation of the complex formed was made with respect to its composition, association constant K(AD)c, molar absorptivity xiAD(A) and free energy change deltaG. The proposed methods were applied successfully to the determination of the cited drugs either in pure or dosage forms with good accuracy and precision. The results were compared statistically with those given by the reported methods.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10701920&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
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 source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10735301&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
Effects of antidepressants in adrenergic neurotransmission of human vas deferens.

Medina P, Segarra G, Ballester R, Chuan P, Domenech C, Vila JM, Lluch S.

Departamento de Fisiologia, Universidad de Valencia, Valencia, Spain.

OBJECTIVES: To evaluate the effects of sertraline, fluoxetine, and amitriptyline on the contractile responses of the human vas deferens muscle elicited by norepinephrine, electrical field stimulation, and KCl, because the therapeutic action of antidepressants may be accompanied by sexual dysfunction related to the contractility of the vas deferens smooth muscle. METHODS: Ring segments of the epididymal part of the vas deferens were taken from 32 elective vasectomies and mounted in organ baths for isometric recording of tension. We then studied the effects of sertraline, fluoxetine, and amitriptyline on the neurogenic and agonist-induced contractile responses. RESULTS: Amitriptyline caused concentration-dependent inhibition of neurogenic and norepinephrine-induced contractions. In contrast, only the highest concentration (10(-5) M) of sertraline and fluoxetine reduced the adrenergic contractions. The dihydropyridine calcium antagonist nifedipine (10(-6) M) completely prevented the inhibitory effect of sertraline and fluoxetine on neurogenic and norepinephrine-induced contractions but did not change the inhibition caused by amitriptyline. Sertraline, fluoxetine, and amitriptyline (all at 10(-5) M) attenuated contractions elicited by KCl and reduced contractions induced by CaCl(2) in KCl-depolarized preparations. CONCLUSIONS: The results indicate that sertraline and fluoxetine inhibit vas deferens motility through inhibition of Ca(2+) entry, with no effect on the adrenergic receptors, and amitriptyline acts as an adrenoceptor antagonist and inhibitor of the entry of calcium.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10736518&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
Inhibitory effect of serotonergic drugs on contractile response of the rat vas deferens to electrical nerve stimulation: in vivo study.

Kim SC, Seo KK, Han JH, Lee MY.

Department of Urology and Physiology, College of Medicine, Chung-Ang University, Seoul, Korea.

PURPOSE: To evaluate, in vivo, the inhibitory effects of certain serotonergic drugs on the contractile response of the rat seminal tract to electrical stimulation of the hypogastric nerve. MATERIALS AND METHODS: Twenty-five Sprague Dawley rats (250 to 300 gm. each) were equally divided into 5 groups based on experimental agent; normal saline, clomipramine, sertraline, paroxetine, and fluoxetine. The hypogastric nerve was electrically stimulated and the intraluminal pressure of the vas deferens was measured, both pretreatment and 30 minutes after intravenous injection of four different doses (0.1 to 20 x the therapeutic dose) of each agent. Variations of responses relative to the time after administration of each agent (at 10- and 20-fold concentration) were also observed. RESULTS: All serotonergic drugs caused dose-dependent inhibition of elevation in intraluminal pressure of the vas deferens (p <0.05). The inhibitory effect of clomipramine was significantly better (p <0. 05) than that of fluoxetine at a 1-fold dose, while no significant differences were noted among clomipramine, sertraline and paroxetine. At doses of 10- and 20-fold, clomipramine had the strongest inhibitory effect, followed by sertraline and paroxetine, then fluoxetine (p <0.05). No differences were found in the inhibitory effects of the drugs studied, as a function of the time after injection. CONCLUSIONS: Clomipramine was the most potent drug for inhibition of elevation in intraluminal pressure of the rat vas deferens induced by electrical stimulation of the rat hypogastric nerve. The stronger inhibitory effect of clomipramine than the selective serotonin reuptake blockers suggests a possible peripheral action of clomipramine in addition to its central serotonergic action.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10799244&dopt=Abstract sertraline Zoloft