Fast-Acting Black-Phosphorus-Assisted Depression Therapy with Low Toxicity.

A black phosphorus (BP)-nanosheet-based drug-delivery system containing a therapeutic drug (Fluoxetine, Flu) is synthesized. According to subsequent behavioral, biochemical, and electrophysiological analysis, BP-Flu, after irradiated with near-infrared light (808 nm), can significantly reduce the therapy time of depression. Meanwhile, the inherent biotoxicity of Flu is also alleviated.

Molecular determinants of chemical modulation of two-pore domain potassium channels.

The K+ ion channels comprising the two-pore domain (K2P) family have specific biophysical roles in generating the critical regulatory K+ current. Ion flow through K2P channels and, implicitly, channel regulation is mediated by diverse metabolic and physical inputs such as mechanical stimulation, interaction with lipids or endogenous regulators, intra- or extracellular pH, and phosphorylation, while their function can be finely tuned by chemical compounds. In the latter category, some drug-channel interactions can lead to side effects or have clinical action, while identifying novel chemical modulators of K2Ps is an area of intense research. Due to their cellular and therapeutic importance, much attention was turned to these channels in recent years and several experimental approaches have pinpointed the molecular determinants of K2P chemical modulation. Given their unique structural features and properties, chemical modulators act on K2P channels in multiple and diverse ways. In this review, the particularities of K2P modulation by chemical compounds, such as binding modality, affinity, or position, are identified, synthesized, and linked to structural and functional properties in order to refer to how activators and blockers modify channel function and vice versa, focusing on specificity related to protein structure (and its modification) and cross-linking information among different subfamilies.

Photo-Fenton degradation of the pharmaceuticals ciprofloxacin and fluoxetine after anaerobic pre-treatment of hospital effluent.

This work evaluated the photo-Fenton degradation of two pharmaceuticals extensively used in human medicine, ciprofloxacin (CIP), and fluoxetine (FLU) when present in an anaerobic pre-treated hospital effluent (HE) at low concentration (100 µg L-1). Operational parameters such as concentration of hydrogen peroxide, iron, and initial pH as well as the effect of iron citrate complex were evaluated considering the degradation of the pharmaceuticals. Iron citrate complex (Fecit) influenced significantly FLU degradation at pH 4.5 achieving 80 % after 20 min, while with iron nitrate only 36 % degradation was obtained after the same time. However, only a slight effect was observed on CIP degradation, achieving 86 % with Fecit and 75 % with Fe(NO3)3, after 20 min. Samples of HE used in this work were previously treated in an anaerobic reactor followed by sand filtration; however, the presence of pharmaceuticals was detected. Degradation of both FLU and CIP was significantly hindered when present in HE, due to the relatively high content of organic (39.6 mg L-1) and inorganic (12.5 mg L-1) carbon, which may have consumed ·OH in side reactions. However, the iron cycle reduction was not affected by the matrix in the presence of citrate. Despite the recalcitrance of the matrix (no total organic carbon removal), it was possible to achieve over 50 % degradation of both pharmaceuticals after 90 min.

Evaluation of the stability of fluoxetine in pluronic lecithin organogel and the determination of an appropriate beyond-use date.

Fluoxetine is a commonly prescribed psychotropic medication for a variety of behavioral diagnoses in veterinary practice, and fluoxetine in Pluronic lecithin organogel has been used successfully in treating inappropriate urine spraying in felines. Historically, pharmacists have assigned a variety of beyond-use dates to extemporaneously compound drugs in Pluronic lecithin organogel. The objective of this study was to evaluate the stability of fluoxetine in Pluronic lecithin organogel over a period of six months and to determine an appropriate beyond-use date. A stability-indicating high-performance liquid chromatography method for fluoxetine in Pluronic lecithin organogel was validated in our laboratory. Fluoxetine-Pluronic lecithin organogel 50 mg/mL was prepared by a local compounding pharmacy and analyzed by high-performance liquid chromatograph at 0, 7, 14, 21, 28, 45, 60, 90, and 180 days. Physical stability was also assessed by visual observation. At each time point percent of initial concentration was calculated. The beyond-use date was determined as the time period that the samples maintained at least 90 percent of the initial concentration. At 180 days, the mean percent of initial concentration was 99 +/- 1.5 and, visually, the fluoxetine-Pluronic lecithin organogel retained the original color and consistency, without detectable separation of the different phases of Pluronic lecithin organogel. Since fluoxetine was physically stable and retained greater than 90 percent of initial concentration in Pluronic lecithin organogel for 180 days when stored at room temperature and protected from light, a beyond-use date of 180 days is appropriate.

Fluoxetine: a case history of its discovery and preclinical development.

INTRODUCTION: Depression is a multifactorial mood disorder with a high prevalence worldwide. Until now, treatments for depression have focused on the inhibition of monoaminergic reuptake sites, which augment the bioavailability of monoamines in the CNS. Advances in drug discovery have widened the therapeutic options with the synthesis of so-called selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine. AREAS COVERED: The aim of this case history is to describe and discuss the pharmacokinetic and pharmacodynamic profiles of fluoxetine, including its acute effects and the adaptive changes induced after long-term treatment. Furthermore, the authors review the effect of fluoxetine on neuroplasticity and adult neurogenesis. In addition, the article summarises the preclinical behavioural data available on fluoxetine's effects on depressive-like behaviour, anxiety and cognition as well as its effects on other diseases. Finally, the article describes the seminal studies validating the antidepressant effects of fluoxetine. EXPERT OPINION: Fluoxetine is the first selective SSRI that has a recognised clinical efficacy and safety profile. Since its discovery, other molecules that mimic its mechanism of action have been developed, commencing a new age in the treatment of depression. Fluoxetine has also demonstrated utility in the treatment of other disorders for which its prescription has now been approved.

Synthesis of some tropane derivatives of anticipated activity on the reuptake of norepinephrine and/or serotonin.

A variety of tropane derivatives 14a-g were prepared via the reaction of the alcohol analogs 12a and 12b with substituted fluorobenzenes 13a-f. The prepared compounds were tested for their activity and selectivity toward the norepinephrine transporter (NET) and serotonin transporter (SERT) using yohimbine-induced mortality and 5-hydroxytryptophan-induced neurotoxicity in mice, respectively. All the tested compounds were found to be NE and 5-HT reuptake inhibitors except 14d which exhibited selective 5-HT reuptake inhibition activity.

The spermicidal and antitrichomonas activities of SSRI antidepressants.

The study investigated spermicidal and antitrichomonas activities of selective serotonin reuptake inhibitor (SSRI) antidepressants with a view to generate new lead for development of dual-function spermicidal microbicides, which is an urgent global need. Fluoxetine, Sertraline, and Fluvoxamine exhibited both spermicidal and anti-STI (antitrichomonas) activities in vitro, whereas Paroxetine and Citalopram showed only the spermicidal activity. Fluoxetine exhibited better activity profile than the other antidepressant drugs with its spermicidal and antitrichomonas activities being comparable to that of the OTC contraceptive Nonoxynol-9. The non-detergent nature of Fluoxetine and a much lower spermicidal ED50 value (than N-9) may add considerably to its merit as a candidate for microbicidal contraceptive. Thus, the antidepressants exhibiting both spermicidal and antitrichomonas activities might provide useful lead for the development of novel, dual-function spermicidal contraceptives.

Simultaneous quantification of fluoxetine, norfluoxetine, and desipramine using gas chromatography with nitrogen-phosphorus detection.

The combination of fluoxetine (FLU) and desipramine (DMI) has been reported to be useful for the treatment of depression, and these drugs are also known to undergo a metabolic drug-drug interaction because of their effects on cytochrome P-450 2D6. A procedure that separates these two drugs and norfluoxetine (NFLU), the N-demethylated metabolite of FLU, and that allows simultaneous quantification of their levels would be of value and has been developed in our laboratories. The procedure involves an initial extraction into ethyl acetate after basification of the homogenate. The organic phase is retained and taken to dryness; the residue is reconstituted in water and acetylated with acetic anhydride under slightly basic conditions. Ethyl acetate is then used to extract the acetylated compounds from the aqueous medium. The organic layer is taken to dryness and the residue reconstituted in toluene. An aliquot of the solution in toluene is injected directly into a gas chromatograph equipped with a nitrogen-phosphorus detector, a fused silica capillary column, and an integrator/printer. Maprotiline is added to the initial homogenate and carried through the procedure as the internal standard. The assay is rapid and sensitive and has been applied successfully to liver and brain tissue taken from rats treated with FLU, DMI, or the combination.