Approximately 90% of the dose is excreted in urine within 24 hours and less than 1% of the dose is recovered in feces.The elimination half-life of instant-release viloxazine is 2 to 5 hours (2–3 hours in the most reliable studies) and the half-life of extended-release viloxazine is 7.02 ± 4.74 hours. Chemistry
Viloxazine is a racemic compound with two stereoisomers, the (S)-(–)-isomer being five times as pharmacologically active as the (R)-(+)-isomer. History
Viloxazine was discovered by scientists at Imperial Chemical Industries when they recognized that some beta blockers inhibited serotonin reuptake inhibitor activity in the brain at high doses. To improve the ability of their compounds to cross the blood brain barrier, they changed the ethanolamine side chain of beta blockers to a morpholine ring, leading to the synthesis of viloxazine. : 610 : 9  It was first described in the scientific literature as early as 1972.The medication was first marketed in 1974. Viloxazine was not approved for medical use by the FDA. In 1984, the FDA granted the medication an orphan designation for treatment of cataplexy and narcolepsy with the tentative brand name Catatrol. For unknown reasons however, it was never approved or introduced for these uses in the United States. Viloxazine was withdrawn from markets worldwide in 2002 for commercial reasons unrelated to efficacy or safety.As of 2015, Supernus Pharmaceuticals was developing extended release formulations of viloxazine as a treatment for ADHD and major depressive disorder under the names SPN-809 and SPN-812. Viloxazine was approved for the treatment of ADHD in the United States in April 2021.
Research
Viloxazine has undergone two randomized controlled trials for nocturnal enuresis (bedwetting) in children, both of those times versus imipramine. By 1990, it was seen as a less cardiotoxic alternative to imipramine, and to be especially effective in heavy sleepers.In narcolepsy, viloxazine has been shown to suppress auxiliary symptoms such as cataplexy and also abnormal sleep-onset REM without really improving daytime somnolence. In a cross-over trial (56 participants) viloxazine significantly reduced EDS and cataplexy.Viloxazine has also been studied for the treatment of alcoholism, with some success.While viloxazine may have been effective in clinical depression, it did relatively poorly in a double-blind randomized controlled trial versus amisulpride in the treatment of dysthymia. References
External links
"Viloxazine". Drug Information Portal. U.S. National Library of Medicine. Clinical trial number NCT03247530 for "Evaluation of SPN-812 ER Low Dose in Children With ADHD" at ClinicalTrials.gov
Clinical trial number NCT03247543 for "Evaluation of SPN-812 ER High Dose in Children With ADHD" at ClinicalTrials.gov