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Medicinal chemistry is a science applied to the search and discovery of new therapeutic agents for the treatment of various diseases. Therefore, promising structures have been identified; one of these structures is the piperazine moiety, a cyclic molecule containing two nitrogen atoms in positions 1 and 4 as well as four carbon atoms. Many piperazine derivatives have central pharmacological activity that mainly involves the activation of the monoamine pathway. Thus, piperazine derivatives have been the subject of research for many central therapeutic applications, including antipsychotic, antidepressant and anxiolytic applications. Benzylpiperazine is the prototype of piperazine derivatives; this substance is the main component of recreational drugs, partly due to its stimulant and euphoric effects. This paper describes some piperazine derivatives used therapeutically as antipsychotic (clozapine), antidepressant (vortioxetine) and anxiolytic (buspirone) drugs. [ABSTRACT FROM AUTHOR]

Aim: The aim of this paper is to clarify the inconsistent findings in the association between antidepressant use and the risk of epithelial ovarian cancer (EOC). Methods: This study is a meta‐analysis of observational studies retrieved from the PubMed, EMBASE, and Web of Science databases prior to August 15, 2017. Two researchers independently screened studies and extracted study characteristics and risk estimates. The odds ratios (OR) and 95% confidence intervals (CI) of EOC risk were summarized using an inverse variance weighted random‐effects model. Heterogeneity between studies was assessed with the I2 statistic. Results: Eight case–control studies involving 7878 EOC cases and 73 913 controls were identified. Compared with non‐use, use of antidepressants was not significantly associated with EOC risk (summarized OR = 1.10, 95% CI: 0.91–1.32, I2 = 74.4%). Similar null results were also observed in the use of selective serotonin reuptake inhibitors (OR = 1.04, 95% CI = 0.80–1.35), tricyclic antidepressants (OR = 1.01, 95% CI = 0.79–1.30), and other antidepressant drugs (OR = 0.91, 95% CI = 0.74–1.12). Subgroup analyses of study characteristics, stratified by the type of control subjects, geographic location, exposure assessment, number of cases, and adjustment for potential confounders, showed that the ORs were broadly consistent across strata. The OR per 1 year‐increment of duration was 0.99 (95% CI = 0.94–1.05, I2 = 40.0%, P = 0.154). Additionally, the OR for the greatest intensity of antidepressant use compared with never use was 0.82 (95% CI = 0.70–0.98, I2 = 0%, P = 0.489). Furthermore, no evidence of publication bias was detected through Funnel plots as well as Egger's and Begg's tests. Conclusions: There is no association between antidepressant use and EOC risk. Further prospective studies are warranted to confirm these findings. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is one of the most disabling diseases worldwide and is becoming a significant public health threat. Current treatments forMDDprimarily consist of monoamine-targeting agents and have limited efficacy. However, the glutamate neurotransmitter system has recently come into focus as a promising alternative for novel antidepressant treatments. We review the current data on the glutamate NMDA receptor antagonist ketamine, which has been shown in clinical trials to act as a rapid antidepressant inMDD.We also examine ketamine efficacy on dimensions of psychopathology, including anhedonia, cognition, and suicidality, consistent with theNIMH Research Domain Criteria initiative. Other aspects of ketamine reviewed in this paper include safety and efficacy, different administration methods, and the risks of misuse of ketamine outside of medical settings. Finally, we conclude with a discussion of glutamatergic agents other than ketamine currently being tested as novel antidepressants. [ABSTRACT FROM AUTHOR]

This paper presents commentaries on whether Starling's law applies to the esophagus; whether erythromycin affects esophageal motility; the relationship between hypertensive lower esophageal sphincter and vigorous achalasia; whether ethnic- and gender-based norms affect diagnosis and treatment of esophageal motor disorders; health care and epidemiology of chest pain; whether normal pH excludes esophageal pain; the role of high-resolution manometry in noncardiac chest pain; whether pH-impedance should be included in the evaluation of noncardiac chest pain; whether there are there alternative therapeutic options to PPI for treating noncardiac chest pain; and the usefulness of psychological treatment and alternative medicine in noncardiac chest pain. [ABSTRACT FROM AUTHOR]

In this paper an attempt is described to measure the cost differential between treating episodes of overdose on older antidepressants (e.g. TCAs) and those involving newer antidepressants (e.g. SSRIs). Data is presented showing that it is possible to demonstrate a marked cost differential between older and newer agents; although there are difficulties in precisely quantifying the difference. The limitations of the data are discussed and recommendations made for the methodology of a larger, more sensitive, study. Copyright © 1999 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background and Purpose Experimental Approach Key Results Conclusions and Implications Demand for new antidepressants has resulted in a re‐evaluation of the therapeutic potential of psychedelic drugs. Several tryptamines found in psilocybin‐containing “magic” mushrooms share chemical similarities with psilocybin. Early work suggests they may share biological targets. However, few studies have explored their pharmacological and behavioural effects.We compared baeocystin, norbaeocystin and aeruginascin with psilocybin to determine if they are metabolized by the same enzymes, similarly penetrate the blood–brain barrier, serve as ligands for similar receptors and modulate behaviour in rodents similarly. We also assessed the stability and optimal storage and handling conditions for each compound.In vitro enzyme kinetics assays found that all compounds had nearly identical rates of dephosphorylation via alkaline phosphatase and metabolism by monoamine oxidase. Further, we found that only the dephosphorylated products of baeocystin and norbaeocystin crossed a blood–brain barrier mimetic to a similar degree as the dephosphorylated form of psilocybin, psilocin. The dephosphorylated form of norbaeocystin was found to activate the 5‐HT2A receptor with similar efficacy to psilocin and norpsilocin in in vitro cell imaging assays. Behaviourally, only psilocybin induced head twitch responses in rats, a marker of 5‐HT2A‐mediated psychedelic effects and hallucinogenic potential. However, like psilocybin, norbaeocystin improved outcomes in the forced swim test. All compounds caused minimal changes to metrics of renal and hepatic health, suggesting innocuous safety profiles.Collectively, this work suggests that other naturally occurring tryptamines, especially norbaeocystin, may share overlapping therapeutic potential with psilocybin, but without causing hallucinations. [ABSTRACT FROM AUTHOR]