sertraline, Zoloft
Sertraline, a serotonin-uptake inhibitor, reduces food intake and body weight in lean rats and genetically obese mice.

Nielsen JA, Chapin DS, Johnson JL Jr, Torgersen LK.

Department of Neuroscience, Pfizer Central Research, Groton, CT 06340.

Sertraline was found to inhibit weight gain and decrease food intake without affecting locomotion in rats and genetically obese (ob/ob) mice. Doses of 10, 17.8, and 32 mg/kg, administered intraperitoneally, (bid) significantly reduced the time rats spent in contact with their feeders and body weight in a dose-related manner. During a 5-d bid treatment regimen, vehicle-treated rats gained 37 +/- 3 g (mean +/- SEM), whereas animals treated with 32 mg sertraline/kg lost 34 +/- 4 g. The effects of sertraline on feeding and body weight in rats appeared to be specific because locomotor activity was not altered. In ob/ob mice, sertraline (44 mg/kg, ip, bid) lowered body weight relative to vehicle-treated controls for the duration of a 12-d study. There was no evidence for tolerance to the hypophagic and weight-loss effects of sertraline during either of the chronic dosing studies. These results suggest a potential role for sertraline in the treatment of human obesity.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1728832&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
Clinical implications of the pharmacology of sertraline.

Warrington SJ.

Charterhouse Clinical Research Unit Limited, London, UK.

Sertraline is slowly absorbed after oral administration, with peak plasma concentrations at 6-8 h. Plasma concentrations are linearly related to dose. The elimination half-life is about 32 h; metabolism is by demethylation to an inactive metabolite. Once-daily dosing is recommended, with steady state being reached after about 7 days. The kinetics of sertraline in the elderly and in patients with renal impairment are similar to those in young healthy female volunteers. In young male volunteers, peak plasma concentrations were lower, and elimination half-life shorter, than in elderly men or both groups of women. Nevertheless, no reduction in dosage is recommended for these groups. Sertraline is highly active in animal models of depression, and administration of the drug to healthy human beings causes a selective, dose-related inhibition of 5-hydroxytryptamine (5-HT) uptake into blood platelets. Single doses of sertraline in volunteers caused changes in the quantitative pharmaco-electroencephalogram suggesting antidepressant and anxiolytic actions, with sedative potential evident only at doses of 200 mg or more. Sertraline does not impair psychomotor performance, including simulated car driving, and overall seems neither stimulating nor sedating: an increase in critical flicker fusion threshold suggests a slight alerting effect, whereas subjective tests indicate an increase in perceived sedation at doses of 100 mg or more. No potentiation of the effects of ethanol has been noted in either young or elderly subjects. No adverse effects on the electrocardiogram, blood pressure, or systolic time intervals have been detected, and sertraline lacks anticholinergic action. These studies imply a low probability of adverse central nervous and cardiovascular effects. Sertraline is probably a weak inducer of hepatic microsomal enzyme activity. Sertraline does not affect the clearance of lithium but there may be a pharmacodynamic interaction which leads to increased tremor when the drugs are given together. No clinically relevant effects were noted in the interaction studies with digoxin, atenolol and diazepam. The pharmacokinetics and pharmacodynamics of sertraline are generally favourable. However, caution is needed when sertraline is given to patients receiving lithium or drugs with a low therapeutic ratio, such as corticosteroids, oral hypoglycaemic agents, and warfarin.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1806626&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
Placental passage of antidepressant medications.

Hendrick V, Stowe ZN, Altshuler LL, Hwang S, Lee E, Haynes D.

Mood Disorders Research Program, UCLA Neuropsychiatric Institute and Hospital, University of California-Los Angeles, 300 Medical Plaza, Suite 2345, Los Angeles, CA 90095, USA. vhendric ucla.edu

OBJECTIVE: This study determined the placental transfer of antidepressants and their metabolites. METHOD: A total of 38 pregnant women taking citalopram, fluoxetine, paroxetine, or sertraline participated. Maternal and umbilical cord blood samples were obtained to determine antidepressant and metabolite concentrations. RESULTS: Antidepressant and metabolite concentrations were detectable in 86.8% of umbilical cord samples. The mean ratios of umbilical cord to maternal serum concentrations ranged from 0.29 to 0.89. The lowest ratios were for sertraline and paroxetine; the highest were for citalopram and fluoxetine. Maternal doses of sertraline and fluoxetine correlated with umbilical cord concentrations of these medications. CONCLUSIONS: Umbilical cord concentrations of antidepressants and their metabolites were almost invariably lower than corresponding maternal concentrations. Maternal doses predicted umbilical concentrations of fluoxetine and sertraline. Mean umbilical cord to maternal serum ratios were significantly lower for sertraline than fluoxetine, suggesting that sertraline may produce less fetal medication exposure than fluoxetine near delivery.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12727706&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
Alcohol drinking attenuated by sertraline in rats with 6-OHDA or 5,7-DHT lesions of N. accumbens: a caloric response?

Myers RD, Quarfordt SD.

Department of Pharmacology, School of Medicine, East Carolina University, Greenville, NC 27858.

The purpose of this study was to elucidate further the role of serotonin (5-HT) in the preference for ethyl alcohol induced in the Sprague-Dawley rat by lesions of the N. accumbens. Following a standard preference test for 3-30% alcohol, dopaminergic or serotonergic neurons in the N. accumbens of the rat were lesioned bilaterally by 6-hydroxydopamine (6-OHDA) or 5,7-dihydroxytryptamine (5,7-DHT), respectively. After recovery postoperatively, each rat was offered water and its maximally preferred concentration of alcohol, which ranged from 7% to 11%. Following a 4-day pretest, either the saline control vehicle or the 5-HT reuptake inhibitor, sertraline, was injected subcutaneously in a dose of either 3.0 or 10 mg/kg b.i.d. at 0800 and 2000 h over the next 3 days. Alcohol preference during the injection sequence and for 4 days thereafter was significantly reduced by sertraline in terms of both absolute g/kg and proportion of alcohol to water intakes. Saline was without effect on alcohol drinking. Comparisons of the drinking profiles of serotonergic versus dopaminergic lesioned rats revealed a dose dependent response to sertraline only in the 5,7-DHT lesioned animals. Although sertraline did not alter water drinking, the consumption of food declined significantly during and after its administration with a decline in body weight also observed at the higher dose. These results suggest that in addition to dopaminergic neurons in the N. accumbens, the synaptic activity of 5-HT in this structure contributes to the aberrant drinking of alcohol. However, this interpretation is tempered by the fact that caloric intake was suppressed concomitantly by the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

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sertraline, Zoloft
Role of central serotonergic neurons in the effect of sertraline in rats in the forced swimming test.

Cervo L, Grignaschi G, Rossi C, Samanin R.

Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.

Sertraline, administered i.p. in single doses or as three injections in 24 h, significantly reduced the immobility of rats in the forced swimming test at 64 and 100 mumol/kg. The effect of three doses of 64 mumol/kg in 24 h was not modified in animals treated i.p. with metergoline (5 mg/kg) 3 h before testing. I.c.v. administration of 150 micrograms 5,7-dihydroxytryptamine, which depleted brain serotonin, or infusion of 6 micrograms 6-hydroxydopamine in the locus coeruleus, which markedly depleted noradrenaline in terminal regions, was also ineffective. The effect of 64 mumol/kg sertraline, once daily for 7 days, was not modified by i.c.v. 5,7-dihydroxytryptamine. The effect of three doses of 64 mumol/kg sertraline in 24 h was instead completely antagonized by 100 mg/kg sulpiride given 90 min before testing. The exact mechanism of this effect and its relevance for the favourable effects of sertraline in human depression remain to be clarified.

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sertraline, Zoloft
Sertraline and cocaine-induced locomotion in mice. I. Acute studies.

Reith ME, Wiener HL, Fischette CT.

Center for Neurochemistry, N.S. Kline Institute for Psychiatric Research, New York, NY 10035.

The present study assessed the behavioral and pharmacokinetic interaction between the serotonin uptake blocker sertraline and cocaine in C57BL/6ByJ mice. Pretreatment with sertraline (1-32 mg/kg IP) did not affect the total amount of spontaneous locomotor activity during 50 min following administration of cocaine (15-40 mg/kg IP). At doses of sertraline (16 and 32 mg/kg) much higher than those found to inhibit ex vivo neuronal uptake of serotonin by 50% (1-2 mg/kg), the peak of cocaine-induced locomotor activity was shifted towards a later time. A similar effect was seen after pretreatment with serotonin uptake blockers other than sertraline, and also after desipramine. Sertraline (16 and 32 mg/kg), given 60 min prior to cocaine, did not affect levels of cocaine in brain and plasma, and cocaine administration did not alter the brain level of sertraline. Although female mice were more responsive to cocaine than male mice, they were not different in their response to sertraline.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2057535&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
Sertraline and cocaine-induced locomotion in mice. II. Chronic studies.

Reith ME, Fischette CT.

Center for Neurochemistry, N.S. Kline Institute for Psychiatric Research, New York, NY 10035.

The effects of repeated treatment with the serotonin uptake blocker sertraline on cocaine-induced locomotion in female C57BL/6ByJ mice were examined in three paradigms. First, when animals were treated for 2 weeks with a daily injection of 8 mg/kg IP of sertraline (or placebo) and challenged with cocaine (25 mg/kg IP) 1 h after the final sertraline injection, their cocaine-induced locomotion was the same as that of placebo-pretreated controls. Second, animals were treated for 2 weeks with cocaine (25 mg/kg IP once a day) (or saline) and then for 2 weeks with sertraline (8 mg/kg IP once a day) (or placebo). Locomotion induced by cocaine (25 mg/kg IP) administered 1 h after the final sertraline (placebo) injection was higher in cocaine- than saline-pretreated mice (sensitization), but there was no difference between sertraline- and placebo-pretreated animals. Third, daily treatment with sertraline (8 mg/kg IP) did not change the locomotor stimulatory effect of cocaine (25 mg/kg IP) administered after a 3-week continuous infusion of cocaine (22 mg/kg/day SC) by osmotic minipumps or after three, four, or seven injections of cocaine (15 or 25 mg/kg IP). After cocaine administration (25 mg/kg IP), animals pretreated repeatedly with sertraline (8 mg/kg IP once a day for 2 weeks) had the same plasma or brain levels of cocaine as those pretreated with placebo; there was no difference between cocaine- and saline-treated mice in brain levels of sertraline or desmethylsertraline.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2057536&dopt=Abstract sertraline Zoloft