viloxazine

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/10/02 03:22:32」(JST)

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Viloxazine

Systematic (IUPAC) name
(RS)-2-[(2-ethoxyphenoxy)methyl]morpholine
Clinical data
Legal status	Not a controlled substance
Routes of administration	Oral, intravenous (infusion)
Pharmacokinetic data
Biological half-life	2-5 hours
Excretion	Renal
Identifiers
CAS Registry Number	46817-91-8 35604-67-2 (HCl salt)
ATC code	N06AX09
PubChem	CID: 5666
ChemSpider	5464 Y
UNII	5I5Y2789ZF Y
KEGG	D08673 Y
ChEMBL	CHEMBL306700 Y
Chemical data
Formula	C13H19NO3
Molecular mass	237.295 g/mol
SMILES O(c1ccccc1OCC)CC2OCCNC2
InChI 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 Y Key:YWPHCCPCQOJSGZ-UHFFFAOYSA-N Y
N (what is this?)  (verify)

Viloxazine (Vivalan, Emovit, Vivarint, Vicilan) is a morpholine derivative and is a selective norepinephrine reuptake inhibitor (NRI). It was used as an antidepressant in some European countries, and produced a stimulant effect that is similar to the amphetamines, except without any signs of dependence. It was discovered and brought to market in 1976 by Imperial Chemical Industries and was withdrawn from the market in the early 2000s for business reasons.

Uses

Viloxazine hydrochloride was used in some European countries for the treatment of clinical depression.

Side effects

Side effects included nausea, vomiting, insomnia, loss of appetite, increased erythrocyte sedimentation, EKG and EEG anomalies, epigastric pain, diarrhea, constipation, vertigo, orthostatic hypotension, edema of the lower extremities, dysarthria, tremor, psychomotor agitation, mental confusion, inappropriate secretion of antidiuretic hormone, increased transaminases, seizure, (there were three cases worldwide, and most animal studies (and clinical trials that included epilepsy patients) indicated the presence of anticonvulsant properties, so was not completely contraindicated in epilepsy,) and increased libido.

Drug interactions

Viloxazine increased plasma levels of phenytoin by an average of 37%. It also was known to significantly increase plasma levels of theophylline and decrease its clearance from the body, sometimes resulting in accidental overdose of theophylline.

Mechanism of action

Viloxazine, like imipramine, inhibited norepinephrine reuptake in the hearts of rats and mice; unlike imipramine, it did not block reuptake of norepinephrine in either the medullae or the hypothalami of rats. As for serotonin, while its reuptake inhibition was comparable to that of desipramine (i.e., very weak), viloxazine did potentiate serotonin-mediated brain functions in a manner similar to amitriptyline and imipramine, which are relatively potent inhibitors of serotonin reuptake. Unlike any of the other drugs tested, it did not exhibit any anticholinergic effects.

It was also found to up-regulate GABA_B receptors in the frontal cortex of rats.

Chemical properties

It 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. The drug was first marketed in 1976. It was never approved by the FDA, but the FDA granted it an orphan designation (but not approval) for cataplexy and narcolepsy in 1984. It was withdrawn from markets worldwide in 2002 for business reasons.

As of 2015, Supernus Pharmaceuticals was developing formulations of viloxazine as a treatment for ADHD and major depressive disorder under the names SPN-809 and SPN-812.

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.

See also

• Teniloxazine
• Reboxetine

References

English Journal

• Characterizing the interaction between enantiomers of eight psychoactive drugs and highly sulfated-β-cyclodextrin by counter-current capillary electrophoresis.

• Asensi-Bernardi L, Escuder-Gilabert L, Martín-Biosca Y, Sagrado S, Medina-Hernández MJ.SourceDepartamento de Química Analítica, Universidad de Valencia, Burjassot, Valencia, Spain.
• Biomedical chromatography : BMC.Biomed Chromatogr.2013 Jun 4. doi: 10.1002/bmc.2935. [Epub ahead of print]
• The estimation of apparent binding constants and limit mobilities of the complexes of the enantiomers that characterize the interaction of enantiomers with chiral selectors, in this case highly sulfated β-cyclodextrin, was approached using a simple and economic electrophoretic modality, the complet
• PMID 23733214

• The effects of most commonly prescribed second generation antidepressants on driving ability: a systematic review : 70th Birthday Prof. Riederer.

• Brunnauer A, Laux G.Sourcekbo-Inn-Salzach-Klinikum (gGmbH), Academic Hospital of Psychiatry Psychotherapy, Psychosomatic Medicine and Neurology, 83512, Wasserburg/Inn, Germany. alexander.brunnauer@iskl.de
• Journal of neural transmission (Vienna, Austria : 1996).J Neural Transm.2013 Jan;120(1):225-32. doi: 10.1007/s00702-012-0833-8. Epub 2012 Jun 9.
• Driving a car is vital for the functional autonomy of patients to take part in activities of daily living. Both psychopathologic symptoms and psychopharmacologic treatment may impair driving ability. This article provides a systematic review of published studies (1980-2011) on commonly prescribed ne
• PMID 22684419

• Determination of antidepressants in human postmortem blood, brain tissue, and hair using gas chromatography-mass spectrometry.

• Wille SM, De Letter EA, Piette MH, Van Overschelde LK, Van Peteghem CH, Lambert WE.SourceLaboratory of Toxicology, Ghent University, Harelbekestraat 72, 9000 Ghent, Belgium.
• International journal of legal medicine.Int J Legal Med.2009 Nov;123(6):451-8. doi: 10.1007/s00414-008-0287-6. Epub 2008 Oct 7.
• A gas chromatographic-mass spectrometric (GC-MS) method in positive ion chemical ionization mode in combination with a solid phase extraction was optimized for new-generation antidepressants and their metabolites in postmortem blood, brain tissue, and hair. Twelve antidepressants and their active me
• PMID 18839201

Japanese Journal

• Carbamazapine-viloxazine interaction in patients with epilepsy

• J Neurol Neurosurg Psychiatry 49, 1142-1145, 1986
• NAID 30041963354

• Increased serum carbamazepine levels by viloxazine in epileptic patients

• Epilepsia 25, 482-485, 1984
• NAID 30030241385

• 非三環系抗うつ剤Vivalan(Viloxazine Hydrochloride)の使用経験

• 精神医学 20(11), p1251-1261, 1978-11
• NAID 40002057204

Related Links

• Viloxazine - Wikipedia, the free encyclopedia

Viloxazine (Vivalan, Emovit, Vivarint, Vicilan) is a bicyclic antidepressant morpholine derivative that acts as a selective norepinephrine reuptake inhibitor ( NRI). It is a racemic compound with two stereoisomers, the (S)-(–)-isomer being five ...

• Viloxazine, sleep, and subjective feelings - Springer

The sleep of eight volunteers (mean age 55) was recorded electrophysiologically while viloxazine 200mg was taken daily for 3 weeks, preceded and followed by a week of matching blanks. The volunteers also made ratings of their feelings on ...