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The compound N-(3-(phenylselanyl)prop-2-yn-1-yl)benzamide (SePB), which combines a selenium atom and a benzamide nucleus in an organic structure, has demonstrated a fast antidepressant-like effect in mice. This action is influenced by the serotonergic system and represents a promising development in the search for novel antidepressant drugs to treat major depressive disorder (MDD), which often resists conventional treatments. This study aimed to further explore the mechanism underlying the antidepressant-like effect of SePB by investigating the involvement of the dopaminergic and noradrenergic systems in the tail suspension test (TST) in mice and evaluating its pharmacokinetic profile in silico. Preadministration of the dopaminergic antagonists haloperidol (0.05 mg/kg, intraperitoneally (i.p.)), a nonselective antagonist of dopamine (DA) receptors, SCH23390 (0.01 mg/kg, subcutaneously (s.c.)), a D1 receptor antagonist, and sulpiride (50 mg/kg, i.p.), a D2/3 receptor antagonist, before SePB (10 mg/kg, intragastrically (i.g.)) prevented the anti-immobility effect of SePB in the TST, demonstrating that these receptors are involved in the antidepressant-like effect of SePB. Administration of the noradrenergic antagonists prazosin (1 mg/kg, i.p.), an α1-adrenergic antagonist, yohimbine (1 mg/kg, i.p.), an α2-adrenergic antagonist, and propranolol (2 mg/kg, i.p.), a ß-adrenergic antagonist, did not block the antidepressant-like effect of SePB on TST, indicating that noradrenergic receptors are not involved in this effect. Additionally, the coadministration of SePB and bupropion (a noradrenaline/dopamine reuptake inhibitor) at subeffective doses (0.1 and 3 mg/kg, respectively) produced antidepressant-like effects. SePB also demonstrated good oral bioavailability and low toxicity in computational absorption, distribution, metabolism, excretion, and toxicity (ADMET) analyses. These findings suggest that SePB has potential as a new antidepressant drug candidate with a particular focus on the dopaminergic system.

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Choosing an appropriate treatment for chronic pain remains problematic, and despite the available medication for its treatment, still, many patients complain about pain and appeal to the use of cannabis derivatives for pain control. However, few data have been provided to clinicians about the pharmacokinetic drug-drug interactions of cannabinoids with other concomitant administered medications. Therefore, the aim of this brief review is to assess the interactions between cannabinoids and pain medication through drug transporters (ATP-binding cassette superfamily members) and/or metabolizing enzymes (cytochromes P450 and glucuronyl transferases).

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We conducted a narrative literature review on studies that specifically addressed the pharmacokinetics of antidepressants in patients on hemodialysis. The search included the MEDLINE, LILACS, and Web of Knowledge databases and combined Medical Subject Headings and free-text search terms for chronic kidney disease, end-stage renal disease, renal replacement therapy, depression, and antidepressants; it was limited to studies conducted in humans, with no language or time constraints. The search yielded 212 studies. After screening titles and abstracts, 32 studies were read in full and 11 ultimately met the inclusion criteria and were included in the review. Most of the studies showed no difference in the pharmacokinetics of antidepressant drugs between patients with normal renal function and patients undergoing hemodialysis. However, studies with fluvoxamine and amitriptyline showed that variations in albumin levels might affect serum concentrations of these agents. The included studies have several limitations, and there are many obstacles to the adequate treatment of depression in patients undergoing hemodialysis. Further studies on this topic are needed to support proper treatment of these patients, improving their quality of life and reducing mortality.

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We conducted a narrative literature review on studies that specifically addressed the pharmacokinetics of antidepressants in patients on hemodialysis. The search included the MEDLINE, LILACS, and Web of Knowledge databases and combined Medical Subject Headings and free-text search terms for chronic kidney disease, end-stage renal disease, renal replacement therapy, depression, and antidepressants; it was limited to studies conducted in humans, with no language or time constraints. The search yielded 212 studies. After screening titles and abstracts, 32 studies were read in full and 11 ultimately met the inclusion criteria and were included in the review. Most of the studies showed no difference in the pharmacokinetics of antidepressant drugs between patients with normal renal function and patients undergoing hemodialysis. However, studies with fluvoxamine and amitriptyline showed that variations in albumin levels might affect serum concentrations of these agents. The included studies have several limitations, and there are many obstacles to the adequate treatment of depression in patients undergoing hemodialysis. Further studies on this topic are needed to support proper treatment of these patients, improving their quality of life and reducing mortality.

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INTRODUCTION: Depression is a serious mood disorder and is one of the most common mental illnesses. Despite the availability of several classes of antidepressants, a substantial percentage of patients are unresponsive to these drugs, which have a slow onset of action in addition to producing undesirable side effects. Some scientific evidence suggests that cyclodextrins (CDs) can improve the physicochemical and pharmacological profile of antidepressant drugs (ADDs). The purpose of this paper is to disclose current data technology prospects involving antidepressant drugs and cyclodextrins. AREAS COVERED: We conducted a patent review to evaluate the antidepressive activity of the compounds complexed in CDs, and we analyzed whether these complexes improved their physicochemical properties and pharmacological action. The present review used 8 specialized patent databases for patent research, using the term 'cyclodextrin' combined with 'antidepressive agents' and its related terms. We found 608 patents. In the end, considering the inclusion criteria, 27 patents reporting the benefits of complexation of ADDs with CDs were included. EXPERT OPINION: The use of CDs can be considered an important tool for the optimization of physicochemical and pharmacological properties of ADDs, such as stability, solubility and bioavailability.

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Se desarrolló una experiencia en una pacientede cambio entre dos marcas comerciales de lamotrigina: Lamictal (referencia) y Epilepax (test). Esto fue motivado por notificaciones sobre sospecha de falta de eficacia de una de las citadas presentaciones farmacéuticas utilizada en el Hospital Vilardebó. Se realizó la comparación de las curvas salivales de lamotrigina versus tiempo para las dos marcas, determinándose parámetros clínicos, farmacocinéticos y de seguridad. La experiencia de cambio entre las dos marcas en la paciente no evidenció diferencias en ninguno de los parámetros mencionados.

An experience was developed in a patient of change between two commercial brands of lamotrigine: Lamictal (reference) and Epilepax (test). This was motivated by notifications on suspicion of lack of efficacy of one of the aforementioned pharmaceutical presentations used in the Vilardebó Hospital. The comparison of salivary curves of lamotrigine versus time for the two brands was made, determining clinical, pharmacokinetic and safety parameters. The experience of change between the two brands in the patient did not show any differences in any of the mentioned parameters.

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Se desarrolló una experiencia en una pacientede cambio entre dos marcas comerciales de lamotrigina: Lamictal (referencia) y Epilepax (test). Esto fue motivado por notificaciones sobre sospecha de falta de eficacia de una de las citadas presentaciones farmacéuticas utilizada en el Hospital Vilardebó. Se realizó la comparación de las curvas salivales de lamotrigina versus tiempo para las dos marcas, determinándose parámetros clínicos, farmacocinéticos y de seguridad. La experiencia de cambio entre las dos marcas en la paciente no evidenció diferencias en ninguno de los parámetros mencionados.

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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.

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This work describes the development of a simple, sensitive and selective method based on high-performance liquid chromatography coupled to tandem mass spectrometry (LC-MS-MS) to determine antipsychotics (olanzapine, quetiapine, clozapine, haloperidol and chlorpromazine) along with antidepressants (mirtazapine, paroxetine, citalopram, sertraline, imipramine, clomipramine and fluoxetine), anticonvulsants (carbamazepine and lamotrigine) and anxiolytics (diazepam and clonazepam) in plasma samples obtained from schizophrenic patients. The samples were prepared by protein precipitation. The target drugs were separated on an XSelect SCH C18 column (100 mm × 2.1 mm × 2.5 µm) within 8.0 min by means of gradient elution. The drugs were then detected on a quadrupole tandem mass spectrometer equipped with an electrospray ionization source, operating in the multiple reactions monitoring mode and in the positive ionization mode. The LC-MS-MS method was linear range from subtherapeutic to toxic concentrations with lower limit of quantification values ranged from 0.2 to 5.0 ng mL(-1), precision with coefficient of variation values lower than 12%, and accuracy ranged from 90 to 108%. The developed method enabled successful analysis of the target drugs in plasma samples obtained from 51 schizophrenic patients. Therapeutic drug monitoring revealed that many of the evaluated schizophrenic patients presented altered plasma concentrations of the analyzed drugs. These altered concentrations resulted from pharmacokinetic interactions among the medications prescribed to treat schizophrenia.

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The purpose of this study was to investigate cyclobenzaprine pharmacokinetics and to evaluate bioequivalence between two different tablet formulations containing the drug. An open, randomized, crossover, single-dose, two-period, and two-sequence design was employed. Tablets were administered to 23 healthy subjects after an overnight fasting and blood samples were collected up to 240 hours after drug administration. Plasma cyclobenzaprine was quantified by means of an LC-MS/MS method. Pharmacokinetic parameters related to absorption, distribution, and elimination were calculated. Cyclobenzaprine plasma profiles for the reference and test products were similar, as well as absorption pharmacokinetic parameters AUC (reference: 199.4 ng ∗ h/mL; test: 201.6 ng ∗ h/mL), Cmax (reference: 7.0 ng/mL; test: 7.2 ng/mL), and T(max) (reference: 4.5 h; test: 4.6 h). Bioequivalence was evaluated by means of 90% confidence intervals for the ratio of AUC (93%-111%) and C(max) (93%-112%) values for test and reference products, which were within the 80%-125% interval proposed by FDA. Cyclobenzaprine pharmacokinetics can be described by a multicompartment open model with an average rapid elimination half-life (t(1/2)ß) of 3.1 hours and an average terminal elimination half-life (t(1/2)γ) of 31.9 hours.

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