In the current study the ability of copper complex to exert multiple biological activities is combined with the pharmacological action of sertraline (SerHCl, antidepressant drug). The hydrated and anhydrous forms of the tetrachlorocuprate(II) salts, namely (SerH)[CuCl]·½HO and (SerH)[CuCl], were synthesized and characterized by physicochemical methods. The crystal structures were determined by X-ray diffraction methods. The hydrate complex crystallizes in the monoclinic P2 space group with a=8.0807(2) Å, b=36.2781(8) Å, c=12.6576(3) Å, β=95.665(2)°, and Z=4 molecules per unit cell and the un-hydrate in P2 with a=13.8727(6) Å, b=7.5090(3) Å, c=18.618(1) Å, β=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 (IC=6.3×10M). The ability of the complex to act as bromoperoxidase mimic was assessed. A pseudo-first order constant of k=0.157±0.007min has been determined. The complex evidences promising biological-pharmacological activities and the albumin binding studies showed a K of 2.90×10M showing an improvement in the uptake of sertraline by albumin at 8h incubation (time required for effective interaction of sertraline with the protein).
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-Met¼S-methyl-L-cysteine) being more effective and remarkable than ZnCl 2 . 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. UVvis studies on the inhibition of acid phosphatase enzyme (AcP) demonstrated that S-methyl-Lcysteine 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.
Background: Magnesium is an essential element related with biochemistry of the brain and different types of depression have been associated with its deficiency. Methods: The structure of a novel magnesium bis(DL-pyroglutamate) (Mg(DL-pGlu) 2 ) was elucidated by X-ray crystallography. Wistar rats were used in the in vivo experiments. The antidepressant-like effect was assessed by the forced swim test (FST) and the antinociceptive activity was evaluated using hot plate test. In both, non-specific effects were evaluated by the open field test. Anti-thyroid activity was examined using Lang's method. Albumin binding behavior was evaluated by 3D fluorescence spectroscopy.Results: For the Mg(DL-pGlu) 2 complex (30 mg/kg), the FST test on Wistar rats revealed a decrease of 22% in the immobility time and an increment of 106% in the swimming time. The compound alters neither the locomotor activity nor the body weight after chronic administration. At the same dose, it showed antinociceptive activity, increasing the response latency. It blocks iodination reactions generating a charge transfer complex with iodine hence indicating anti-thyroid activity (K c = 45366.5 AE 29 M À1 ). Albumin 3D fluorescence spectroscopy experiments showed intensity increase of peak A and decrease of peak B. Conclusions: The results showed that the new compound produced a lowering of the immobility time and an increment of the swimming ability of the rats. The compound is able to increase the response latency in 70.0%, to capture iodine (anti-thyroid activity) and to interact with albumin through covalent type of interaction of the free NH groups.
A study was conducted in two groups of healthy volunteers to assess whether the time of administration (10 min before the meal versus 60 min after the meal) influences the pharmacokinetics and absorption kinetics of a slow-release theophylline product (Teonova). In the first group (Group A, n = 10), the drug was given in a paired-sample design as a single dose of 600 mg before and after breakfast with an interval of at least 1 week between the two administrations. In the second group (Group B, n = 10), Teonova was given by the same study design before and after dinner. In all cases, time curves of theophylline plasma levels were determined by collecting serial blood samples 24 h after dosing and analysed pharmacokinetically through model-independent methods. In Group A, curves obtained before and after the meal were fully superimposable, and no difference was found between the pharmacokinetic parameters determined in either condition. The same result was obtained in Group B. Our results indicate that, after single dose, the two different times of administration that we tested were equivalent in pharmacokinetic terms.
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