Sertraline HCl

Sertraline hydrochloride is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class.

Spectrophotometric Determination of the Antidepressants Sertraline and Paroxetine HCl using 2,4-Dinitrofluorobenzene.[Pubmed:23675200]

Int J Biomed Sci. 2010 Sep;6(3):252-9.

A simple and sensitive spectrophotometric method was developed for the determination of each of sertraline (SER) and paroxetine HCl (PXT) in dosage forms. The method is based upon reaction of PXT and SER with 2,4-dinitrofluorobenzene (DNFB) to form colored products. The absorbance of the products were measured at 375and 390 nm for SER and PXT respectively. The absorbance concentration plots were rectilinear over the concentration rang of 1-10 and 2-20 mug/mL with lower detection limits (LOD) of 0.11 and 0.28 mug/mL and quantification limits (LOQ) of 0.32 and 0.85 mug/mL for SER and PXT, respectively. The developed method was successfully applied for the determination of SER and PXT in dosage forms. The common excipients and additives did not interfere in their determinations. There was no significant difference between the results obtained by the proposed and the reference methods regarding Student t-test and the variance ratio F-test respectively. A proposal of the reaction pathway was postulated.

Concurrent administration of donepezil HCl and sertraline HCl in healthy volunteers: assessment of pharmacokinetic changes and safety following single and multiple oral doses.[Pubmed:15496220]

Br J Clin Pharmacol. 2004 Nov;58 Suppl 1:25-33.

AIM: This study evaluated the safety and pharmacokinetics (PK) of donepezil HCl and Sertraline HCl when administered separately and in combination. METHODS: This was a randomized, open-label, three-period crossover study. In consecutive dosing periods separated by washout periods of > or = 3 weeks, healthy volunteers received either oral donepezil HCI 5 mg once daily for 15 days, oral Sertraline HCl 50 mg once daily for 5 days followed by 10 days of once-daily Sertraline HCl 100 mg, or the simultaneous administration of oral donepezil HCl and Sertraline HCl. Plasma donepezil and sertraline concentrations were determined by high performance liquid chromatography/mass spectrometry. Safety was evaluated by physical and laboratory evaluations and the monitoring of adverse events (AEs). RESULTS: A total of 19 volunteers (16 male and three female) were enrolled. Three male subjects withdrew from the study prematurely due to AEs (one case of nausea/stomach cramps and one case of eosinophilia during combination treatment, and one upper respiratory tract infection during treatment with Sertraline HCl alone). In subjects who completed all three treatment periods (n = 16), the concurrent administration of donepezil HCl and Sertraline HCl did not alter the steady-state (day 15) PK parameters of donepezil HCl. A small (< 12%) but statistically significant (P = 0.02) increase in donepezil C(max) was seen after single doses of Sertraline HCl and donepezil HCl on day 1 but this was not thought to be clinically meaningful. No significant differences in the t(max) or AUC(0-24 h) of donepezil were observed between the donepezil HCl only or donepezil HCl plus Sertraline HCl groups on day 1. No significant changes in sertraline PK parameters were observed either on day 1 (single dose) or on day 15 (steady state) when Sertraline HCl was co-administered with donepezil HCl. Generally, the concurrent administration of donepezil HCl and Sertraline HCl was well tolerated, with no serious AEs reported during the study. Some digestive system AEs tended to occur more frequently during combination treatment than with either treatment alone, but there was no statistically significant increase in the incidence of any individual AE. The most common AEs during the combination therapy were nausea and diarrhoea, which were rated as mild or moderate in severity. These AEs were also reported during the administration of each drug alone. CONCLUSIONS: The co-administration of once-daily oral donepezil HCl 5 mg for 15 days and once-daily oral Sertraline HCl (50 mg for 5 days increased to 100 mg for 10 days) did not result in any clinically meaningful pharmacokinetic interactions, and no unexpected AEs were observed.

Pharmacology of sertraline: a review.[Pubmed:3045112]

J Clin Psychiatry. 1988 Aug;49 Suppl:40-5.

Sertraline is a member of a new class of psychotherapeutic agents that selectively inhibit serotonin reuptake in the brain. Animal studies have demonstrated that inhibition of serotonin reuptake leads to enhanced serotonergic neurotransmission and indirectly results in a down-regulation of beta-adrenoceptors. The preclinical pharmacology of sertraline predicts antidepressant activity without accompanying anticholinergic, cardiotonic, or sedative side effects. Recent laboratory and clinical observations pertaining to body weight and obsessive compulsive disorder suggest the possibility of broader clinical indications for selective serotonin reuptake blockers such as sertraline.

Sertraline, 1S,4S-N-methyl-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-naphthylamine, a new uptake inhibitor with selectivity for serotonin.[Pubmed:6310078]

J Pharmacol Exp Ther. 1983 Sep;226(3):686-700.

Sertraline [1S,4S-N-methyl-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-naphthylamine] was found to be a highly selective and potent competitive inhibitor of synaptosomal serotonin uptake. Sertraline also selectively reduced ex vivo uptake of serotonin and strongly antagonized the serotonin-depleting action of p-chloroamphetamine, indicating potent blockade of serotonin uptake in vivo. Acute and repeated dosing of sertraline decreased serotonin content of whole blood. Sertraline only weakly inhibited rat heart uptake of i.v. [3H]norepinephrine. In substantiation of selective blockade of serotonin uptake, sertraline potentiated various symptoms of 5-hydroxytryptophan but did not reverse reserpine-induced hypothermia. Sertraline was a very weak inhibitor of [3H]quinuclidinyl benzilate binding to rat brain membranes in vitro and did not produce anticholinergic effects in mice in vivo. Sertraline was well tolerated in mice, rats and dogs, with no locomotor stimulant effects in rats or untoward cardiovascular effects in dogs. The major metabolite, N-demethylsertraline, was also a selective serotonin uptake blocker. Sertraline strongly reduced immobility of mice in the Porsolt swim test for antidepressants. After repeated dosing in rats, sertraline diminished the cyclic AMP response of limbic forebrain adenylate cyclase to norepinephrine, as well as the binding of [3H]dihydroalprenolol to cortical membranes. It is proposed that selective blockade of serotonin reuptake can induce activation of norepinephrine neurons and subsequent down-regulation of norepinephrine receptors and that sertraline, a highly selective inhibitor of serotonin uptake, may be an efficacious antidepressant without anticholinergic or cardiovascular side-effects.