Uncertainties remain about whether vortioxetine is indeed a clinically multimodal antidepressant or whether it is effectively "[just] another selective serotonin reuptake inhibitor".Antagonism of the 5-HT3 receptor has been found to enhance the increase in brain serotonin levels produced by serotonin reuptake inhibition in animal studies. Whether or not the 5-HT3 receptor antagonism of vortioxetine likewise does this in humans or contributes to its clinical antidepressant efficacy is unclear. SSRIs and 5-HT1A receptor agonists often produce nausea as a side effect, whereas 5-HT3 receptor antagonists like ondansetron are antiemetics and have been found to be effective in treating SSRI-induced nausea. It was thought that the 5-HT3 receptor antagonism of vortioxetine would reduce the incidence of nausea relative to SSRIs. However, clinical trials found significant and dose-dependent rates of nausea with vortioxetine that appeared to be comparable to those found with the SNRI duloxetine. Pharmacokinetics
Vortioxetine is well-absorbed when taken orally and has an oral bioavailability of 75%. It is systemically detectable after a single oral dose by 0.781 hours. Peak levels of vortioxetine are reached within 7 to 11 hours post-dose with single or multiple doses. Steady-state levels of vortioxetine are generally reached within 2 weeks of administration, with 90% of individuals reaching 90% of steady state after 12 days of administration. Steady-state peak levels of vortioxetine with doses of 5, 10, and 20 mg/day were 9, 18, and 33 ng/mL, respectively. The accumulation index of vortioxetine (area-under-the-curve levels after a single dose versus at steady state) is 5 to 6.
Fosdenopterin (or cyclic pyranopterin monophosphate, cPMP), sold under the brand name Nulibry, is a medication used to reduce the risk of death due to a rare genetic disease known as molybdenum cofactor deficiency type A.The most common side effects include complications related to the intravenous line, fever, respiratory infections, vomiting, gastroenteritis, and diarrhea.Fosdenopterin was approved for medical use in the United States in February 2021,  It is the first medication approved by the U.S. Food and Drug Administration (FDA) for the treatment of molybdenum cofactor deficiency type A. and in the European Union in September 2022. Medical uses
Fosdenopterin is indicated to reduce the risk of mortality in people with molybdenum cofactor deficiency  (MoCD) type A. Mechanism of action
People with molybdenum cofactor deficiency type A cannot produce cyclic pyranopterin monophosphate (cPMP) in their body. Fosdenopterin is an intravenous medication that replaces the missing cPMP. cPMP is a precursor to molybdopterin, which is required for the enzyme activity of sulfite oxidase, xanthine dehydrogenase/oxidase and aldehyde oxidase. History
Fosdenopterin was developed at the German universities TU Braunschweig and the University of Cologne.The effectiveness of fosdenopterin for the treatment of MoCD-A was demonstrated in thirteen treated participants compared to eighteen matched, untreated participants. The participants treated with fosdenopterin had a survival rate of 84% at three years, compared to 55% for the untreated participants.The U.S. Food and Drug Administration (FDA) granted the application for fosdenopterin priority review, breakthrough therapy, and orphan drug designations along with a rare pediatric disease priority review voucher.