Viloxazine in ADHD

Viloxazine ((±)-2-[(2-ethoxyphenoxy)methyl]morpholine hydrochloride; C13H20NO3Cl) has been used in the United States since April 2021 to treat ADHD in children and depression. It was used in Europe from 1976 to 2006 as an antidepressant and off-label for enuresis and narcolepsy.

Viloxazine acts as a¹²

• selective norepinephrine reuptake inhibitor
  • thereby increasing dopamine and norepinephrine in the PFC
• Serotonin 5-HT2B receptor antagonist
• Serotonin 5-HT2C receptor agonist
• weak serotonin 5-HT7 receptor antagonist
• weak α1B-adrenoceptor antagonist
• weak β2-adrenoceptor antagonist

Viloxazine has been shown to increase serotonin levels in the PFC.³.However, it does not appear to act as a serotonin reuptake inhibitor.
It does not increase the release of norepinephrine.

Viloxazine markedly increases plasma levels of the adenosine A1 and A2 antagonist theophylline.⁴⁵

It is conceivable that part of the effect of viloxazine in ADHD may be due to the dopamine-enhancing effect of the adenosine antagonist theophylline.

Side effects:

Viloxazine should be avoided in those with a tendency to epilepsy
Increased suicidal tendencies were reported in a small proportion of child subjects.
Viloxazine must not be taken during or if pregnancy is intended, It may harm the fetus.

Dismantling

Viloxazine is metabolized by CYP2D6, UGT1A9, and UGT2B15.⁶ Possibly also by CYP1A2.