Clinical pharmacology, efficacy, and safety of orexin receptor antagonists for the treatment of insomnia disorders.

Introduction: The last two decades have witnessed a rapid increase in the knowledge about the role of the orexin system, particularly in the regulation of wakefulness and arousal. Dual orexin receptor antagonists (DORAs) have been approved for the treatment of insomnia disorders (suvorexant, lemborexant) and drugs with a distinctive profile (daridorexant) or orexin-2 receptor selectivity (seltorexant) are in development.

Areas Covered: This review discusses pharmacokinetics (PK), pharmacodynamics (PD), efficacy, and safety properties of orexin receptor antagonists (ORAs).

Assessment of the pulmonary CYP1A1 metabolism of mavoglurant (AFQ056) in rat.

1. AFQ056 phenotyping results indicate that CYP1A1 is responsible for the formation of the oxidative metabolite, M3. In line with the predominant assumption that CYP1A1 is mainly expressed in extrahepatic tissues, only traces of M3 were detected in hepatic systems.

Comparison of Tunable Diode Laser Absorption Spectroscopy and Isothermal Micro-calorimetry for Non-invasive Detection of Microbial Growth in Media Fills.

Two methods were investigated for non-invasive microbial growth-detection in intact glass vials as possible techniques for automated inspection of media-filled units. Tunable diode laser absorption spectroscopy (TDLAS) was used to determine microbially induced changes in O2 and CO2 concentrations within the vial headspaces. Isothermal microcalorimetry (IMC) allowed the detection of metabolic heat production.

Clinical pharmacology, efficacy, and safety aspects of sphingosine-1-phosphate receptor modulators.

Introduction: Sphingosine-1-phosphate (S1P) receptor modulators, of which one has received marketing approval and several others are in clinical development, display promising potential in the treatment of a spectrum of autoimmune diseases.

Areas Covered: Administration of S1P1 receptor modulators leads to functional receptor antagonism triggering sustained inhibition of the egress of lymphocytes from lymphoid organs. First-dose administration is associated with transient cardiovascular effects.

Risk of Seizures Associated with Antidepressant Use in Patients with Depressive Disorder: Follow-up Study with a Nested Case-Control Analysis Using the Clinical Practice Research Datalink.

Introduction: Antidepressant use has been associated with an increased risk of seizures. Evidence on the association between antidepressant use at therapeutic doses and seizures mainly comes from clinical trials that were not designed to investigate this potential relationship.

Objective: The objective of this study was to assess the risk of first-time seizures in association with exposure to antidepressants in patients with depressive disorders.