VILOXAZINE

Details

Stereochemistry	RACEMIC
Molecular Formula	C13H19NO3
Molecular Weight	237.2949
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

CCOC1=CC=CC=C1OCC2CNCCO2

InChI

InChIKey=YWPHCCPCQOJSGZ-UHFFFAOYSA-N

InChI=1S/C13H19NO3/c1-2-15-12-5-3-4-6-13(12)17-10-11-9-14-7-8-16-11/h3-6,11,14H,2,7-10H2,1H3

HIDE SMILES / InChI

Molecular Formula	C13H19NO3
Molecular Weight	237.2949
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	0 / 1
E/Z Centers	0
Optical Activity	( + / - )

Description

Viloxazine is a selective norepinephrine reuptake inhibitor that has a long history of clinical use in Europe as an antidepressant. An immediate-release formulation was approved for the treatment of depression in the UK in 1974, and was subsequently marketed there and in several European countries for 30 years with no major safety concerns. In April of 2021, the United States Food and Drug Administration (FDA) approved the use of viloxazine (QELBREE), developed by Supernus Pharmaceuticals, for the treatment of attention-deficit/hyperactivity disorder (ADHD) in pediatric and adult patients. Approval was based on positive results from a series of short-term phase III clinical trials in which viloxazine improved the severity of ADHD symptoms in children and adolescents with diagnosed ADHD. Viloxazine is available as extended-release capsules for once-daily oral administration.

CNS Activity

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Sodium-dependent noradrenaline transporter 39	Inhibitor 8,504
Sodium-dependent noradrenaline transporter 39	Inhibitor 8,504		2300.0 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Attention Deficit Hyperactivity Disorder 2	Primary		Approved 8,583	QELBREE

C_max

Value	Dose	Analyte	Population
1.33 μg/mL	200 mg single, oral	VILOXAZINE plasma	Homo sapiens
1.66 μg/mL	200 mg 1 times / day steady-state, oral	VILOXAZINE plasma	Homo sapiens
1.34 μg/mL	200 mg single, oral	VILOXAZINE plasma	Homo sapiens
1.21 μg/mL	200 mg single, oral	VILOXAZINE plasma	Homo sapiens
1.22 μg/mL	200 mg single, oral	VILOXAZINE plasma	Homo sapiens
2.83 μg/mL	400 mg single, oral	VILOXAZINE plasma	Homo sapiens
3.06 μg/mL	400 mg single, oral	VILOXAZINE plasma	Homo sapiens
3.25 μg/mL	400 mg single, oral	VILOXAZINE plasma	Homo sapiens
4.65 μg/mL	400 mg single, oral	VILOXAZINE plasma	Homo sapiens
8 μg/mL	900 mg 1 times / day steady-state, oral	VILOXAZINE plasma	Homo sapiens
6.59 μg/mL	900 mg 1 times / day steady-state, oral	VILOXAZINE plasma	Homo sapiens

AUC

Value	Dose	Analyte	Population
27.3 μg × h/mL	200 mg single, oral	VILOXAZINE plasma	Homo sapiens
24.7 μg × h/mL	200 mg 1 times / day steady-state, oral	VILOXAZINE plasma	Homo sapiens
25.64 μg × h/mL	200 mg single, oral	VILOXAZINE plasma	Homo sapiens
24.45 μg × h/mL	200 mg single, oral	VILOXAZINE plasma	Homo sapiens
23.68 μg × h/mL	200 mg single, oral	VILOXAZINE plasma	Homo sapiens
61.84 μg × h/mL	400 mg single, oral	VILOXAZINE plasma	Homo sapiens
67.59 μg × h/mL	400 mg single, oral	VILOXAZINE plasma	Homo sapiens
80.38 μg × h/mL	400 mg single, oral	VILOXAZINE plasma	Homo sapiens
117.5 μg × h/mL	400 mg single, oral	VILOXAZINE plasma	Homo sapiens
134.32 μg × h/mL	900 mg 1 times / day steady-state, oral	VILOXAZINE plasma	Homo sapiens
106.89 μg × h/mL	900 mg 1 times / day steady-state, oral	VILOXAZINE plasma	Homo sapiens

T_1/2

Value	Dose	Co-administered	Analyte	Population
7.02 h	200 mg single, oral		VILOXAZINE plasma	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
24.3%			VILOXAZINE plasma	Homo sapiens

Doses

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Dose	Population	Adverse events
400 mg 1 times / day steady, oral Highest studied dose	unhealthy	Other AEs: somnolence...
600 mg 1 times / day steady, oral Highest studied dose	unhealthy	Disc. AE: Somnolence, Fatigue...
100 mg 1 times / day steady-state, oral Studied dose	unhealthy	Disc. AE: Fatigue, Tachycardia...
200 mg 1 times / day steady, oral Studied dose	unhealthy	Disc. AE: Somnolence, Abdominal pain...
200 mg 1 times / day steady-state, oral Studied dose	unhealthy	Disc. AE: Somnolence, Abdominal pain...

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AEs

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AE	Significance	Dose	Population
somnolence	1 patient	400 mg 1 times / day steady, oral Highest studied dose	unhealthy
Depression	1% Disc. AE	600 mg 1 times / day steady, oral Highest studied dose	unhealthy
Dizziness	1% Disc. AE	600 mg 1 times / day steady, oral Highest studied dose	unhealthy
Fatigue	1% Disc. AE	600 mg 1 times / day steady, oral Highest studied dose	unhealthy
Tachycardia	1% Disc. AE	600 mg 1 times / day steady, oral Highest studied dose	unhealthy

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Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2,252 substrate 1,946	inhibitor 2,438 inducer 440	substrate 1,388 inhibitor 2,507	inhibitor 2,217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C8 1,057 OAT1 725 OATP1B1 1,079 OAT3 747 OATP1B3 961 CYP2B6 926 CYP1A2 2,153 MATE2-K 77 OCT2 779 BCRP 910 P-gp 1,741 CYP2C19 2,057 MATE1 415	OCT 4 OAT 5 OATP1B3 435 BCRP 697 MATE 2 P-gp 2,052 UGT1A9 423 CYP2B6 776 UGT2B15 236 UGT1A1 479 OATP1B1 503 UGT1A3 470 CYP1A2 1,197 UGT1A6 343 UGT1A4 399 UGT2B7 456	CYP1A2 832 CYP2B6 669 CYP3A4/5 133 CYP1A1 151

Drug as perpetrator

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Target	Modality	Activity
MATE2-K 77	inhibitor 4,027	no [IC50 3300 uM]
CYP2C19 2,141	inhibitor 4,027	no [IC50 >1010 uM]
CYP2C8 1,117	inhibitor 4,027	no [IC50 >1010 uM]
CYP2C9 2,497	inhibitor 4,027	no [IC50 >1010 uM]
BCRP 985	inhibitor 4,027	no [IC50 >150 uM]

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Drug as victim

Show entries

Target	Modality	Activity	Metabolite
UGT1A4 399	substrate 4,014		5-hydroxyviloxazine 2
BCRP 697	substrate 4,014	no
MATE 2	substrate 4,014	no
OAT 5	substrate 4,014	no
OATP1B1 503	substrate 4,014	no

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Tox targets

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Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2,263	inhibitor 2,237

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PubMed

Show entries

Title	Date	PubMed
[Comparative evaluation of the therapeutic efficacy of the antidepressants adepren, linamiphen and emovit].	1986	3716711
Stereochemistry and drug efficacy and development: relevance of chirality to antidepressant and antipsychotic drugs.	2002	12553493
Contribution of sleep research to the development of new antidepressants.	2005	16416706
Development of a solid phase extraction for 13 'new' generation antidepressants and their active metabolites for gas chromatographic-mass spectrometric analysis.	2005 Dec 9	16314157
Enhancing central noradrenergic function in depression: is there still a place for a new antidepressant?	2005 Mar	18568121

Showing 1 to 5 of 7 entries

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Patents

Sample Use Guides

In Vivo Use Guide

Treatment of Attention Deficit Hyperactivity Disorder in adults: Recommended starting dosage is 200 mg once daily. May titrate in increments of 200 mg weekly, to maximum recommended dosage of 600 mg once daily.

Route of Administration: Oral

In Vitro Use Guide

Viloxazine exhibits an inhibitory effect on NE uptake, with an inhibitory constant (Ki) of 2300 nM in rat hypothalamic synaptosomes uptake assay.