Improving the antidepressant action of sertraline by co-crystallization with the antioxidant agent coumarin 3-carboxylic acid. Structural determinations.

G.E. ESCUDERO; C.H. LAINO; GUSTAVO ETCHEVERRÍA; O.E.PIRO; N. MARTINI; RODRÍGUEZ AN; J..J. MARTÍNEZ MEDINA; L. L. LÓPEZ TÉVEZ; E. G. FERRER; P. A. M. WILLIAMS

CHEMICO-BIOLOGICAL INTERACTIONS

ELSEVIER IRELAND LTD

Lugar: Dublin; Año: 2016 vol. 249 p. 46 - 55

0009-2797

To improve the antidepressant action of sertraline a new salt with coumarin-3-carboxylate anion (SerHCCA)has been synthesized by two different methods and characterized by FTIR spectroscopy andstructural determinations by X-ray diffraction methods. The new salt is stabilized by strong intermolecularH-bonds involving the protonated amine group of SerH and the deprotonated carboxylate groupof CCA. These findings can be correlated with the interpretation of the infrared spectrum. The salt,sertraline (SerHCl) and the sodium salt of coumarin-3-carboxylate (NaCCA) were orally administeredmale Wistar rats (10 mg/kg, based on sertraline). Rats were evaluated in separate groups by means of theforced swimming (FST). SerH-CCA produced antidepressant effects in a magnitude that exceeded SerHClindividual effects. None of these treatments affected activity levels by the open field OFT tests. We havealso determined that the ion pair also improve the binding to bovine serum albumin (BSA) of the drugbut retain its antimicrobial activity. It is reasonable to conclude that the replacement of chloride anion bya large organic anion in sertraline strengthens the pharmacological action of the native drug, binding toBSA with higher activity and retaining the antimicrobial activity of the antidepressant compound.