Viloxazine

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Viloxazine
Viloxazine.svg
Systematic (IUPAC) name
(RS)-2-[(2-ethoxyphenoxy)methyl]morpholine[1]
Clinical data
Legal status Not a controlled substance
Routes Oral, intravenous (infusion)[2]
Pharmacokinetic data
Excretion Renal[3]
Identifiers
CAS number 46817-91-8 N 46817-91-8[4]
35604-67-2 (HCl salt)
ATC code N06AX09
PubChem CID 5666
ChemSpider 5464 YesY
UNII 5I5Y2789ZF YesY
KEGG D08673 YesY
ChEMBL CHEMBL306700 YesY
Chemical data
Formula C13H19NO3 
Mol. mass 237.295 g/mol
 N (what is this?)  (verify)

Viloxazine (Vivalan, Emovit, Vivarint, Vicilan) is a bicyclic antidepressant[5] morpholine derivative that acts as a selective norepinephrine reuptake inhibitor (NRI).[6] It is a racemic compound with two stereoisomers, the (S)-(–)-isomer being five times as pharmacologically active as the (R)-(+)-isomer.[7]

Uses[edit]

Approved[edit]

Viloxazine hydrochloride was approved in Italy, Belgium, England, Ireland, Germany, Portugal, Spain, the former Yugoslavia, France, Slovakia,[8] for the treatment of clinical depression.[9]

Unapproved/off-Label/investigational[edit]

Viloxazine has undergone two randomized controlled trials for nocturnal enuresis (bedwetting) in children, both of those times versus imipramine.[10],[11] By 1990, it was seen as a less cardiotoxic alternative to imipramine, and to be especially effective in heavy sleepers.[12]

In narcolepsy, viloxazine has been shown to suppress auxiliary symptoms such as cataplexy and also abnormal sleep-onset REM[13] without really improving daytime somnolence.[14]

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.[15]

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.[16]

Mechanism of action[edit]

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 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.[17] Unlike any of the other drugs tested, it did not exhibit any anticholinergic effects.[18]

It is also known to up-regulate GABAB receptors in the frontal cortex.[19]

Side effects[edit]

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,[20]) and increased libido.[21]

Drug interactions[edit]

Viloxazine is known to increase plasma levels of phenytoin by an average of 37%.[22] It is also known to significantly increase plasma levels of theophylline and decrease its clearance from the body,[23] sometimes resulting in accidental overdose of theophylline.[24]

See also[edit]

References[edit]

  1. ^ "SID 180462-- PubChem Substance Summary". Retrieved 5 November 2005. 
  2. ^ "MEDLINE subject headings for Viloxazine". Retrieved 5 November 2005. 
  3. ^ Case DE, Reeves PR (February 1975). "The disposition and metabolism of I.C.I. 58,834 (viloxazine) in humans". Xenobiotica 5 (2): 113–29. doi:10.3109/00498257509056097. PMID 1154799. 
  4. ^ Bouchard JM, Strub N, Nil R (October 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. doi:10.1016/S0165-0327(97)00078-5. PMID 9387086. 
  5. ^ 【合法】個人輸入代行薬【未認可】 (The relevant section is English[citation needed])
  6. ^ Müller-Oerlinghausen B, Rüther E (July 1979). "Clinical profile and serum concentration of viloxazine as compared to amitriptyline". Pharmakopsychiatrie, Neuro-Psychopharmakologie 12 (4): 321–37. doi:10.1055/s-0028-1094627. PMID 386390. 
  7. ^ Danchev ND, Rozhanets VV, Zhmurenko LA, Glozman OM, Zagorevskiĭ VA (May 1984). "Behavioral and radioreceptor analysis of viloxazine stereoisomers" [Behavioral and radioreceptor analysis of viloxazine stereoisomers]. Biulleten' Eksperimental'noĭ Biologii i Meditsiny (in Russian) 97 (5): 576–8. PMID 6326891. 
  8. ^ AstraZeneca Slovensko (2000). "VIVALAN tbl obd". Retrieved 2005-11-05. [dead link]
  9. ^ AstraZeneca International (2003). "Vivalan (viloxazine hydrochloride)". Retrieved 2005-11-06. 
  10. ^ Attenburrow AA, Stanley TV, Holland RP (January 1984). "Nocturnal enuresis: a study". The Practitioner 228 (1387): 99–102. PMID 6364124. 
  11. ^ 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. 
  12. ^ Libert MH (1990). "The use of viloxazine in the treatment of primary enuresis" [The use of viloxazine in the treatment of primary enuresis]. Acta Urologica Belgica (in French) 58 (1): 117–22. PMID 2371930. 
  13. ^ 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. 
  14. ^ Mitler MM, Hajdukovic R, Erman M, Koziol JA (January 1990). "Narcolepsy". Journal of Clinical Neurophysiology 7 (1): 93–118. doi:10.1097/00004691-199001000-00008. PMC 2254143. PMID 1968069. 
  15. ^ 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. 
  16. ^ León CA, Vigoya J, Conde S, Campo G, Castrillón E, León A (March 1994). "Comparison of the effect of amisulpride and viloxazine in the treatment of dysthymia" [Comparison of the effect of amisulpride and viloxazine in the treatment of dysthymia]. Acta Psiquiátrica Y Psicológica de América Latina (in Spanish) 40 (1): 41–9. PMID 8053353. 
  17. ^ Lippman W, Pugsley TA (August 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. doi:10.1139/y76-069. PMID 974878. 
  18. ^ see Lippman and Pugsley, 1976.
  19. ^ Lloyd KG, Thuret F, Pilc A (October 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". The Journal of Pharmacology and Experimental Therapeutics 235 (1): 191–9. PMID 2995646. 
  20. ^ Edwards JG, Glen-Bott M (September 1984). "Does viloxazine have epileptogenic properties?". Journal of Neurology, Neurosurgery, and Psychiatry 47 (9): 960–4. doi:10.1136/jnnp.47.9.960. PMC 1027998. PMID 6434699. 
  21. ^ Chebili S, Abaoub A, Mezouane B, Le Goff JF (1998). "Antidepressants and sexual stimulation: the correlation" [Antidepressants and sexual stimulation: the correlation]. L'Encéphale (in French) 24 (3): 180–4. PMID 9696909. 
  22. ^ Pisani F, Fazio A, Artesi C, et al. (February 1992). "Elevation of plasma phenytoin by viloxazine in epileptic patients: a clinically significant drug interaction". Journal of Neurology, Neurosurgery, and Psychiatry 55 (2): 126–7. doi:10.1136/jnnp.55.2.126. PMC 488975. PMID 1538217. 
  23. ^ Perault MC, Griesemann E, Bouquet S, Lavoisy J, Vandel B (September 1989). "A study of the interaction of viloxazine with theophylline". Therapeutic Drug Monitoring 11 (5): 520–2. doi:10.1097/00007691-198909000-00005. PMID 2815226. 
  24. ^ 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.