RESUMEN
In the current study the ability of copper complex to exert multiple biological activities is combined with the pharmacological action of sertraline (SerH2Cl, antidepressant drug). The hydrated and anhydrous forms of the tetrachlorocuprate(II) salts, namely (SerH2)2[CuCl4]·½H2O and (SerH2)2[CuCl4], were synthesized and characterized by physicochemical methods. The crystal structures were determined by X-ray diffraction methods. The hydrate complex crystallizes in the monoclinic P21 space group with a=8.0807(2) Å, b=36.2781(8) Å, c=12.6576(3) Å, ß=95.665(2)°, and Z=4 molecules per unit cell and the un-hydrate in P21 with a=13.8727(6) Å, b=7.5090(3) Å, c=18.618(1) Å, ß=104.563(6)°, and Z=2. It has been suggested that Cu(II) ions might be critical in the development of mood disorders, showed potent biocidal activity, and also acted as analgesic adjuvant. To improve sertraline efficiency, the antidepressant and analgesic activities of the complex have been assessed in rats denoting a marked synergistic effect. Antithyroid and antimicrobial activities were also evaluated. Because depressive disorders and hyperthyroidism diseases led to an oxidative stress state, antioxidant capability has also been tested. The complex behaved as a good superoxide radical scavenger (IC50=6.3×10-6M). The ability of the complex to act as bromoperoxidase mimic was assessed. A pseudo-first order constant of k=0.157±0.007min-1 has been determined. The complex evidences promising biological-pharmacological activities and the albumin binding studies showed a Kb of 2.90×103M-1 showing an improvement in the uptake of sertraline by albumin at 8h incubation (time required for effective interaction of sertraline with the protein).
Asunto(s)
Analgésicos , Antiinfecciosos , Antidepresivos , Complejos de Coordinación , Cobre , Sertralina , Analgésicos/síntesis química , Analgésicos/química , Analgésicos/farmacología , Animales , Antiinfecciosos/síntesis química , Antiinfecciosos/química , Antiinfecciosos/farmacología , Antidepresivos/síntesis química , Antidepresivos/química , Antidepresivos/farmacología , Bovinos , Complejos de Coordinación/síntesis química , Complejos de Coordinación/química , Cobre/química , Cobre/farmacología , Masculino , Ratas , Ratas Wistar , Sertralina/química , Sertralina/farmacologíaRESUMEN
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.
Asunto(s)
Antidepresivos/química , Antidepresivos/farmacocinética , Cumarinas/química , Sertralina/química , Sertralina/farmacocinética , Animales , Antiinfecciosos/química , Antiinfecciosos/farmacocinética , Antiinfecciosos/farmacología , Antidepresivos/farmacología , Disponibilidad Biológica , Cristalización/métodos , Depresión/tratamiento farmacológico , Masculino , Actividad Motora/efectos de los fármacos , Ratas , Ratas Wistar , Sertralina/farmacología , Natación/fisiología , Difracción de Rayos X/métodosRESUMEN
The antidepressant effect of simple Zn(II) salts has been proved in several animal models of depression. In this study, a coordination metal complex of Zn(II) having a sulfur containing ligand is tested as antidepressant for the first time. Forced swimming test method on male Wistar rats shows a decrease in the immobility and an increase in the swimming behavior after treatment with [Zn(S-Met)2] (S-Met=S-methyl-l-cysteine) being more effective and remarkable than ZnCl2. The thiobarbituric acid and the pyranine consumption (hydroxyl and peroxyl radicals, respectively) methods were applied to evaluate the antioxidant activity of S-Met and [Zn(S-Met)2] showing evidence of attenuation of hydroxyl but not peroxyl radicals activities. UV-vis studies on the inhibition of acid phosphatase enzyme (AcP) demonstrated that S-methyl-l-cysteine did not produce any effect but, in contrast, [Zn(S-Met)2] complex behaved as a moderate inhibitor. Finally, bioavailability studies were performed by fluorescence spectroscopy denoting the ability of the albumin to transport the complex.
Asunto(s)
Antidepresivos/farmacología , Cisteína/análogos & derivados , Inhibidores Enzimáticos/farmacología , Depuradores de Radicales Libres/farmacología , Zinc/química , Animales , Antidepresivos/química , Cisteína/química , Cisteína/farmacología , Inhibidores Enzimáticos/química , Depuradores de Radicales Libres/química , Masculino , Ratas , Ratas Wistar , NataciónRESUMEN
OBJECTIVES: Recent evidence associates omega-3 fatty acids (O3) with pain reduction. The aim of this work was to evaluate the antinociceptive effect of O3, either alone or in combination with morphine after acute and chronic administration in rats. As well, a new pharmaceutical mixture that allows the concomitant administration of O3 and morphine as an oral solution was developed. METHODS: Animals were fed on a control or an experimental diet supplemented with O3. They were subjected to the hot-plate test to assess analgesic effect and tolerance to the analgesic effect of morphine. The open-field test was carried out to determine if the differences in the response latency can be related to non-specific sedative effects. KEY FINDINGS: O3 dietary supplementation increased the response latency compared with the control group. Acute treatment with morphine in these groups resulted in an additive antinociceptive effect not related to locomotor activity. Chronic coadministration of morphine with O3 attenuated the development of tolerance. Oral administration of the new pharmaceutical mixture showed analgesic activity with a subtherapeutic dose of morphine. CONCLUSION: This finding suggests a role for O3 as adjuncts to opioids in pain therapy and might contribute to the reduction of the occurrence of morphine side-effects.
Asunto(s)
Analgésicos/farmacología , Ácidos Grasos Omega-3/administración & dosificación , Morfina/farmacología , Analgesia/métodos , Animales , Sinergismo Farmacológico , Quimioterapia Combinada/métodos , Tolerancia a Medicamentos/fisiología , Calor/efectos adversos , Masculino , Dolor/tratamiento farmacológico , Manejo del Dolor/métodos , Dimensión del Dolor/métodos , Ratas WistarRESUMEN
Mayor depression, obsessive-compulsive panic, social anxiety disorders are common diseases that are usually treated with sertraline hydrochloride which is the active ingredient of the well known drugs as Zoloft and Lustral. In this work, we presented a more complete vibrational characterization of the solid phase FT-IR spectra of Sertraline hydrochloride and its sertraline-iodine product in which the conformational space of the molecules was investigated performing molecular dynamic simulations within an NVT ensemble. Geometrical, electronic and vibrational properties were calculated with the density functional theory. Comparison of the simulated spectra with the experimental spectra provides important information about the ability of the computational method to describe the vibrational modes of both molecules. In addition, for the first time we present the evaluation of anti-thyroid activity of sertraline hydrochloride by using the Lang's method. Also, with the aim to evaluate the antidepressant effect of its iodine product we demonstrated for this compound the toxic effect towards the male Wistar rats.