Sertraline HCl(CAS 79559-97-0) is a 5-HT antagonist with Ki
of 13 nM.
Sertraline exhibits better selectivity for inhibiting 5-HT uptake relative to NE uptake than fluvoxamine, zimelidine, norzimelidine, fluoxetine or chlorimipramine. However, Sertraline is less selective for blocking 5-HT uptake, relative to DA uptake than these agents.
Sertraline HCl (32μmol/kg i.p.) inhibits serotonin uptake into striatal synaptosomes from rats by more than 50%. Sertraline HCl is 6 times more potent than chlorimipramine and 60 times more potent than amitriptyline in reversing the 5-HT depletion elicited by PCA. Acute and repeated dosing of sertraline decreased serotonin content of whole blood. Sertraline HCl strongly reduces immobility of mice in the Porsolt swim test for antidepressants.
Sertraline free base is also available as I009444
1:Br J Clin Pharmacol. 2004 Nov;58 Suppl 1:25-33. Concurrent administration of donepezil HCl and sertraline HCl in healthy volunteers: assessment of pharmacokinetic changes and safety following single and multiple oral doses.Nagy CF,Kumar D,Perdomo CA,Wason S,Cullen EI,Pratt RD, PMID: 15496220 PMCID: PMC1884554 DOI: 10.1111/j.1365-2125.2004.01801.x<br />
<span>Abstract:</span> 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.