Collated from TripSit, Pharmacology, DrugCentral, DailyMed. Where sources differ (e.g. dosing), Compare shows them side by side.
NRI that was used as an antidepressant in some European countries, and had a pronouced stimulant effect similar to amphetamines without any signs of dependence. Withdrawn in the early 2000s.TS
Oral
Route dataTripSit
| Threshold | Light | Common | Strong | Heavy |
|---|---|---|---|---|
| — | 50–75 mg | 75–150 mg | — | —+ |
| Onset | 15–30 minutes |
|---|---|
| Total | 3–6 hours |
🧬 Receptor activityPHDC
| Target | Action | Affinity | Source | |
|---|---|---|---|---|
| Norepinephrine transporter | — | Ki 170 nM | CHEMBL | TargetNorepinephrine transporter Action— AffinityKi 170 nM SourceCHEMBL |
| Sodium-dependent serotonin transporter | — | Ki 16500 nM | CHEMBL | TargetSodium-dependent serotonin transporter Action— AffinityKi 16500 nM SourceCHEMBL |
| Sodium-dependent dopamine transporter | — | Ki 48000 nM | CHEMBL | TargetSodium-dependent dopamine transporter Action— AffinityKi 48000 nM SourceCHEMBL |
| Sodium-dependent noradrenaline transporter (SLC6A2) | Antagonist | 6.7 IC50 | DRUGCENTRAL | TargetSodium-dependent noradrenaline transporter (SLC6A2) ActionAntagonist Affinity6.7 IC50 SourceDRUGCENTRAL |
| Sodium-dependent dopamine transporter (SLC6A3) | — | 6.81 Kd | DRUGCENTRAL | TargetSodium-dependent dopamine transporter (SLC6A3) Action— Affinity6.81 Kd SourceDRUGCENTRAL |
| Sodium-dependent serotonin transporter (SLC6A4) | — | 4.76 Kd | DRUGCENTRAL | TargetSodium-dependent serotonin transporter (SLC6A4) Action— Affinity4.76 Kd SourceDRUGCENTRAL |
| Transporter (Slc6a2) | — | 6.77 Ki | DRUGCENTRAL | TargetTransporter (Slc6a2) Action— Affinity6.77 Ki SourceDRUGCENTRAL |
Mechanism of actionPHDM
Attention Deficit Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder in children characterized by inattention and hyperactivity. In current literature, the pathophysiology of ADHD is understood to involve the imbalance of neurotransmitters, especially dopamine (DA) and norepinephrine (NE). The mechanism of action of viloxazine has not been fully elucidated; however, viloxazine is believed to work by modulating the monoaminergic neurotransmitter systems. Viloxazine is a selective and moderate norepinephrine reuptake inhibitor that binds to the norepinephrine transporter and inhibits the reuptake of norepinephrine. It thereby increases extracellular norepinephrine levels across several brain regions. Viloxazine potentiates serotonergic effects: it was shown to enhance neuronal sensitivity to serotonin and increase serotonin levels in the brain. _In vitro_, viloxazine is an antagonist at 5-HT<sub>2B</sub> receptors and an agonist 5-HT<sub>2C</sub> receptors. 5-HT<sub>2B</sub> receptors expressed on GABAergic interneurons are involved in tonic inhibitory control of serotonin neurons that innervate the medial prefrontal context; thus, antagonism of 5-HT<sub>2B</sub> receptors may result in disinhibition and enhanced serotonin release in the brain region. There is conflicting evidence in the literature that viloxazine increases dopamine levels in the brain via direct or indirect effects. For example, the norepinephrine transporter is also involved in the reuptake of dopamine in the prefrontal cortex and stimulation of 5-HT<sub>2C</sub> receptors facilitates DA release and enhances dopaminergic transmission in the brain. As dopamine dysregulation in the prefrontal cortex and amygdala is implicated in ADHD pathophysiology, the impact of viloxazine on dopamine levels may contribute to its mechanism of action. However, there is insufficient evidence to conclude this. Viloxazine has a negligible impact on dopamine in the nucleus accumbens and is not associated with an abuse risk.
PharmacodynamicsPHDM
Viloxazine is a serotonin-norepinephrine modulating agent that has been used as a treatment for depression and Attention Deficit Hyperactivity Disorder (ADHD). Although it is not a stimulant agent, viloxazine produces amphetamine-like CNS stimulant effects without a risk for drug abuse or dependence. Viloxazine does not produce sedative anticholinergic or adrenergic effects.
Pharmacokinetics
Half-lifePH
The mean (± SD) half-life of viloxazine was 7.02 (± 4.74) hours.
AbsorptionPHDM
Viloxazine is rapidly absorbed following oral administration. The relative bioavailability of viloxazine extended-release relative to an immediate-release formulation was about 88%. Viloxazine Cmax and AUC increase proportionally over a dosage range from 100 mg to 600 mg once daily. The Cmax ranges between 540 and 1600 ng/mL. Following administration of a single 200 mg dose, the median Tmax was approximately five hours, with a range of three to nine hours. Steady-state was reached after two days of once-daily administration, and no accumulation was observed. A high-fat meal decreases Cmax and AUC by about 9% and 8%, respectively, and delays Tmax by two hours.
Viloxazine is primarily excreted via renal elimination. After administration of radiolabeled viloxazine, 90% of the dose was recovered in urine within the first 24 hours post-dose. Less than 1% of the dose is excreted in the feces. About 12-15% of the total drug is eliminated as unchanged parent drug.
The volume of distribution was 0.73 ± 0.28 L/kg following intravenous administration.
The clearance rate was 124 ± 11 mL/hour/kg following intravenous administration.
MetabolismPH
Viloxazine undergoes CYP2D6-mediated 5-hydroxylation to form 5-hydroxyviloxazine. This metabolite can be glucuronidated by UGT1A9 and UGT2B15 to form 5-hydroxyviloxazine glucuronide, which is the major metabolite detected in plasma. Viloxazine can also be glucuronidated to form Viloxazine N-carbamoyl glucuronide.
Protein bindingPH
Viloxazine is 76-82% bound to human plasma proteins over the blood concentration range of 0.5 mcg/mL to 10 mcg/mL.
Plan a dose of Viloxazine
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