Viloxazine

Viloxazine

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Systematic (IUPAC) name
(RS)-2-[(2-ethoxyphenoxy)methyl]morpholine
Clinical data
Routes of administration	Oral, intravenous (infusion)
Legal status
Legal status	Not a controlled substance
Pharmacokinetic data
Excretion	Renal
Identifiers
CAS Number	46817-91-8 46817-91-8 35604-67-2 (HCl salt)
ATC code	N06AX09 (WHO)
PubChem	CID 5666
Chemical data
Formula	C13H19NO3
Molar mass	237.295 g/mol[[]]

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 times as pharmacologically active as the (R)-(+)-isomer.

Uses

Approved

Viloxazine hydrochloride was approved in Italy, Belgium, the United States, England, Ireland, Germany, Portugal, Spain, the former Yugoslavia, France, Slovakia, for the treatment of clinical depression.

Unapproved/Off-Label/Investigational

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. {ref Vignatelli L, D'Alessandro R, Candelise L. Antidepressant drugs for narcolepsy. Cochrane Database of Systematic Reviews 2007, Issue 4. Art. No.: CD003724. DOI: 10.1002/14651858.CD003724.pub3}

Viloxazine has also been studied for the treatment of alcoholism, with some success.

While viloxazine may be effective in clinical depression, it did relatively poorly in a double-blind randomized controlled trial versus amisulpride in the treatment of dysthymia, according to Leon and colleagues at the University of Valle in Colombia.

Mechanism of Action

In 1976, Lippman and Pugsley reported that viloxazine, like imipramine, inhibited norepinephrine reuptake in the hearts of rats and mice; unlike imipramine, (or desipramine or amitriptyline, for that matter) it did not block reuptake of norepinephrine in neither the medullae nor 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 is also known to up-regulate GABA_B receptors in the frontal cortex.

Side Effects

Side effects include 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 is not completely contraindicated in epilepsy), and increased libido.

Drug Interactions

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

References

1. ^ "SID 180462-- PubChem Substance Summary". Retrieved 5 November 2005. 
2. ^ "MEDLINE subject headings for Viloxazine". Retrieved 5 November 2005. 
3. ^ Biam (1999) VILOXAZINE CHLORHYDRATE, MORPHOLINES [online] Available from: http://www.biam2.org/www/Sub3399.html Accessed on 5 November 2005. (French)
4. ^
5. ^
6. ^ 【合法】個人輸入代行薬【未認可】 (The relevant section is English)
7. ^
8. ^
9. ^ Biam (1999) see Biam, 1999.
10. ^ AstraZeneca Slovensko (2000). "VIVALAN tbl obd". Retrieved 2005-11-05. 
11. ^ AstraZeneca International (2003). "Vivalan (viloxazine hydrochloride)". Retrieved 2005-11-06. 
12. ^
13. ^ Yurdakök M, Kinik E, Güvenç H, Bedük Y (1987). "Viloxazine versus imipramine in the treatment of enuresis". The Turkish Journal of Pediatrics. 29 (4): 227–30. PMID 3332732. CS1 maint: Multiple names: authors list (link)
14. ^
15. ^ Guilleminault C, Mancuso J, Salva MA; et al. (1986). "Viloxazine hydrochloride in narcolepsy: a preliminary report". Sleep. 9 (1 Pt 2): 275–9. PMID 3704453. CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
16. ^
17. ^ Altamura AC, Mauri MC, Girardi T, Panetta B (1990). "Alcoholism and depression: a placebo controlled study with viloxazine". International Journal of Clinical Pharmacology Research. 10 (5): 293–8. PMID 2079386. CS1 maint: Multiple names: authors list (link)
18. ^
19. ^
20. ^ see Lippman and Pugsley, 1976.
21. ^
22. ^ see Biam, 1999.
23. ^
24. ^
25. ^
26. ^
27. ^ Laaban JP, Dupeyron JP, Lafay M, Sofeir M, Rochemaure J, Fabiani P (1986). "Theophylline intoxication following viloxazine induced decrease in clearance". European Journal of Clinical Pharmacology. 30 (3): 351–3. doi:10.1007/BF00541543. PMID 3732375. CS1 maint: Multiple names: authors list (link)

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