title: Improving the antidepressant action and the bioavailability of sertraline by co-crystallization with coumarin 3-carboxylate. Structural determination.
abstract: To improve the antidepressant action of sertraline a new salt with coumarin-3-carboxylate anion (SerH-CCA) has been synthesized by two different methods and characterized by FTIR spectroscopy and structural determinations by X-ray diffraction methods. The new salt is stabilized by strong intermolecular H-bonds involving the protonated amine group of SerH and the deprotonated carboxylate group of 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 administered male Wistar rats (10 mg/kg, based on sertraline). Rats were evaluated in separate groups by means of the forced swimming (FST). SerH-CCA produced antidepressant effects in a magnitude that exceeded SerHCl individual effects. None of these treatments affected activity levels by the open field OFT tests. We have also determined that the ion pair also improve the binding to bovine serum albumin (BSA) of the drug but retain its antimicrobial activity. It is reasonable to conclude that the replacement of chloride anion by a large organic anion in sertraline strengthens the pharmacological action of the native drug, binding to BSA with higher activity and retaining the antimicrobial activity of the antidepressant compound.
authors.affiliation: Instituto de Bioquímica y Farmacia (IByF), Centro de Investigación e Innovación Tecnológica (CENIIT), Universidad Nacional de La Rioja, Av. Luis Vernet y Apóstol Felipe, 5300, La Rioja, Argentina.
authors.forename: Graciela E
authors.initials: GE
authors.lastname: Escudero
authors.affiliation: Instituto de Biotecnología, Centro de Investigación e Innovación Tecnológica (CENIIT), Universidad Nacional de La Rioja, Av. Luis Vernet y Apóstol Felipe, 5300, La Rioja, Argentina.
authors.forename: Carlos H
authors.initials: CH
authors.lastname: Laino
authors.affiliation: Departamento de Física, Facultad de Ciencias Exactas, Universidad Nacional de La Plata and IFLP(CONICET, CCT La Plata), C.C. 67, 1900, La Plata, Argentina.
authors.forename: Gustavo A
authors.initials: GA
authors.lastname: Echeverría
authors.affiliation: Departamento de Física, Facultad de Ciencias Exactas, Universidad Nacional de La Plata and IFLP(CONICET, CCT La Plata), C.C. 67, 1900, La Plata, Argentina.
authors.forename: Oscar E
authors.initials: OE
authors.lastname: Piro
authors.affiliation: Centro de Química Inorgánica (CEQUINOR, CONICET, UNLP)-Departamento de Química- Facultad de Ciencias Exactas, Universidad Nacional de La Plata, 47 y 115- C.C.962- (B1900AVV), 1900, La Plata, Argentina.
authors.forename: Nancy
authors.initials: N
authors.lastname: Martini
authors.affiliation: Universidad Nacional del Chaco Austral, Com. Fernández 755, CP 3700, Presidencia Roque Sáenz Peña, Chaco, Argentina.
authors.forename: Ailén N
authors.initials: AN
authors.lastname: Rodríguez
authors.affiliation: Universidad Nacional del Chaco Austral, Com. Fernández 755, CP 3700, Presidencia Roque Sáenz Peña, Chaco, Argentina.
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Martínez Medina
authors.affiliation: Universidad Nacional del Chaco Austral, Com. Fernández 755, CP 3700, Presidencia Roque Sáenz Peña, Chaco, Argentina.
authors.forename: Libertad L
authors.initials: LL
authors.lastname: López Tévez
authors.affiliation: Centro de Química Inorgánica (CEQUINOR, CONICET, UNLP)-Departamento de Química- Facultad de Ciencias Exactas, Universidad Nacional de La Plata, 47 y 115- C.C.962- (B1900AVV), 1900, La Plata, Argentina.
authors.forename: Evelina G
authors.initials: EG
authors.lastname: Ferrer
authors.affiliation: Centro de Química Inorgánica (CEQUINOR, CONICET, UNLP)-Departamento de Química- Facultad de Ciencias Exactas, Universidad Nacional de La Plata, 47 y 115- C.C.962- (B1900AVV), 1900, La Plata, Argentina. Electronic address: williams@quimica.unlp.edu.ar.
authors.forename: Patricia A M
authors.initials: PA
authors.lastname: Williams
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D000928:Antidepressive Agents / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000494:pharmacology; D001682:Biological Availability; D003374:Coumarins / Q000737:chemistry*; D003460:Crystallization / Q000379:methods; D003863:Depression / Q000188:drug therapy; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D020280:Sertraline / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000494:pharmacology; D013550:Swimming / Q000502:physiology; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D000890:Anti-Infective Agents; D000928:Antidepressive Agents; D003374:Coumarins; D020280:Sertraline; C104227:coumarin-3-carboxylic acid
keywords: Antidepressants; BSA binding; Sertraline-coumarin-3-carboxylate; Structural determination; Wistar rat tests