Viloxazine

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Viloxazine
Clinical data
Routes of
administration		Oral, intravenous (infusion)[1]
ATC code
Legal status
Legal status
  • Not a controlled substance
Pharmacokinetic data
ExcretionRenal[2]
Identifiers
CAS Number
PubChem CID
E number{{#property:P628}}
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Chemical and physical data
FormulaC13H19NO3
Molar mass237.295 g/mol

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [6]

Overview

Viloxazine (Emovit®, Vivalan®, Vivarint®, Vicilan®) is a bicyclic antidepressant[7] morpholine derivative that inhibits the reuptake of norepinephrine.[8] It is a racemic compound with two isomers, the S(-)-isomer being five times as pharmacologically active as the R(+)-isomer.[9]

Uses

Approved

Viloxazine hydrochloride was approved in Italy, Belgium, the United States, England, Ireland, Germany, Portugal, Spain, the former Yugoslavia, France,[10] Slovakia,[11] for the treatment of clinical depression.[12]

Unapproved/off-Label/investigational

Viloxazine has undergone two randomized controlled trials for nocturnal enuresis (bed-wetting) in children, both of those times versus imipramine.[13],[14] By 1990, it was seen as a less cardiotoxic alternative to imipramine, and to be especially effective in heavy sleepers.[15]

In narcolepsy, viloxazine has been shown to suppress auxiliary symptoms such as cataplexy and also abnormal sleep-onset REM[16] without really improving daytime somnolence.[17]

Viloxazine has also been studied for the treatment of alcoholism, with some success.[18]

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.[19]

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.[20] Unlike any of the other drugs tested, it did not exhibit any anticholinergic effects.[21]

It is also known to up-regulate GABAB receptors in the frontal cortex.[22]

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,[23] (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[24]), and increased libido.[25]

Drug interactions

Viloxazine is known to increase plasma levels of phenytoin by an average of 37%.[26] It is also known to significantly increase plasma levels of theophylline and decrease its clearance from the body,[27] sometimes resulting in accidental overdose of theophylline.[28]

References

  1. ^ "SID 180462-- PubChem Substance Summary". Retrieved 5 November. Unknown parameter |accessyear= ignored (|access-date= suggested) (help); Check date values in: |accessdate= (help)
  2. ^ "MEDLINE subject headings for Viloxazine". Retrieved 5 November. Unknown parameter |accessyear= ignored (|access-date= suggested) (help); Check date values in: |accessdate= (help)
  3. ^ Biam (1999) VILOXAZINE CHLORHYDRATE, MORPHOLINES [online] Available from: http://www.biam2.org/www/Sub3399.html Accessed on 5 November 2005. (French)
  4. ^ Case DE, Reeves PR (1975). "The disposition and metabolism of I.C.I. 58,834 (viloxazine) in humans". Xenobiotica. 5 (2): 113–29. PMID 1154799. List of Library Holdings Worldwide
  5. ^ Bouchard JM, Strub N, Nil R (1997). "Citalopram and viloxazine in the treatment of depression by means of slow drop infusion. A double-blind comparative trial". Journal of Affective Disorders. 46 (1): 51–8. PMID 9387086. Fulltext options List of Library Holdings Worldwide
  6. ^ 【合法】個人輸入代行薬【未認可】 (The relevant section is English)
  7. ^ Muller-Oerlinghausen B, Ruther E. "Clinical profile and serum concentration of viloxazine as compared to amitriptyline." Pharmakopsychiatr Neuropsychopharmakol. 1979 Jul;12(4):321-37. PMID 386390
  8. ^ Danchev ND, Rozhanets VV, Zhmurenko LA, Glozman OM, Zagorevskii VA (1984). "[Behavioral and radioreceptor analysis of viloxazine stereoisomers]". Biulleten' Eksperimental'noi Biologii i Meditsiny. 97 (5): 576–8. [Article in Russian] PMID 6326891 List of Library Holdings Worldwide
  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. ^ Attenburrow AA, Stanley TV, Holland RP (1984). "Nocturnal enuresis: a study". The Practitioner. 228 (1387): 99–102. PMID 6364124. List of Library Holdings Worldwide
  13. ^ Yurdakok M, Kinik E, Guvenc H, Beduk Y (1987). "Viloxazine versus imipramine in the treatment of enuresis". The Turkish Journal of Pediatrics. 29 (4): 227–30. PMID 3332732. List of Library Holdings Worldwide
  14. ^ Libert MH (1990). "[The use of viloxazine in the treatment of primary enuresis]". Acta Urologica Belgica. 58 (1): 117–22. [Article in French] PMID 2371930 List of Library Holdings Worldwide
  15. ^ Guilleminault C, Mancuso J, Salva MA, Hayes B, Mitler M, Poirier G, Montplaisir J (1986). "Viloxazine hydrochloride in narcolepsy: a preliminary report". Sleep. 9 (1 Pt 2): 275–9. PMID 3704453. List of Library Holdings Worldwide
  16. ^ Mitler MM, Hajdukovic R, Erman M, Koziol JA (1990). "Narcolepsy". Journal of Clinical Neurophysiology. 7 (1): 93–118. PMID 1968069. List of Library Holdings Worldwide
  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. List of Library Holdings Worldwide
  18. ^ Leon CA, Vigoya J, Conde S, Campo G, Castrillon E, Leon A (1994). "[Comparison of the effect of amisulpride and viloxazine in the treatment of dysthymia]". Acta Psiquiatrica y Psicologica de America Latina. 40 (1): 41–9. [Article in Spanish] PMID 8053353 List of Library Holdings Worldwide
  19. ^ Lippman W, Pugsley TA. (1976). "Effects of viloxazine, an antidepressant agent, on biogenic amine uptake mechanisms and related activities". Canadian Journal of Physiology and Pharmacology. 54 (4): 494–509. PMID 974878. List of Library Holdings Worldwide
  20. ^ see Lippman and Pugsley, 1976.
  21. ^ Lloyd KG, Thuret F, Pilc A (1985). "Upregulation of gamma-aminobutyric acid (GABA) B binding sites in rat frontal cortex: a common action of repeated administration of different classes of antidepressants and electroshock". Journal of Pharmacology & Experimental Therapeutics. 235 (1): 191–9. PMID 2995646. List of Library Holdings Worldwide
  22. ^ see Biam, 1999.
  23. ^ Edwards JG, Glen-Bott M (1984). "Does viloxazine have epileptogenic properties?". Journal of Neurology, Neurosurgery, and Psychiatry. 47 (9): 960–4. PMID 6434699. List of Library Holdings Worldwide
  24. ^ Chebili S, Abaoub A, Mezouane B, Le Goff JF (1998). "[Antidepressants and sexual stimulation: the correlation]". L'Encephale. 24 (3): 180–4. [Article in French] PMID 9696909 List of Library Holdings Worldwide
  25. ^ F Pisani, A Fazio, C Artesi, M Russo, R Trio, G Oteri, E Perucca and R Di Perri (1992). "Elevation of plasma phenytoin by viloxazine in epileptic patients: a clinically significant drug interaction". Journal of Neurology, Neurosurgery, and Psychiatry. 55 (2): 126–127. PMID 1538217. List of Library Holdings Worldwide
  26. ^ Perault MC, Griesemann E, Bouquet S, Lavoisy J, Vandel B (1989). "A study of the interaction of viloxazine with theophylline". Therapeutic Drug Monitoring. 11 (5): 520–2. PMID 2815226. List of Library Holdings Worldwide
  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. PMID 3732375. List of Library Holdings Worldwide


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