Viloxazine

Drugbox
IUPAC_name = "2- [(2-ethoxyphenoxy)methyl] morpholine"ref|iupacformula

---

CAS_number=46817-91-8
CAS_supplemental= [http://www.nlm.nih.gov/cgi/mesh/2006/MB_cgi?term=46817-91-8&rn=1 46817-91-8] ref|cas_from_MeSH 35604-67-2 (HCl salt)ref|cas_from_biam
ATC_prefix=N06
ATC_suffix=AX09
ATC_supplemental=
PubChem=5666
DrugBank=
C = 13 | H = 19 | N = 1 | O = 3
molecular_weight = 237.295 g/mol
bioavailability=
metabolism =
elimination_half-life=
excretion = Renalref|renal
pregnancy_category =
legal_status = Not a controlled substance
routes_of_administration= Oral, intravenous (infusion)ref|intravenous

Viloxazine (Emovit, Vivalan, Vivarint, Vicilan) is a bicyclic antidepressantref|bicyclic morpholine derivative that inhibits the reuptake of norepinephrine.ref|nari It is a racemic compound with two isomers, the S(-)-isomer being five times as pharmacologically active as the R(+)-isomer.ref|isomer

Uses

Approved

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

Unapproved/off-Label/investigational

Viloxazine has undergone two randomized controlled trials for nocturnal enuresis (bed-wetting) in children, both of those times versus imipramine.ref|Attenburrow_et_al_1984^,ref|Yurdakok_et_al_1987 By 1990, it was seen as a less cardiotoxic alternative to imipramine, and to be especially effective in heavy sleepers.ref|Libert_1990

In narcolepsy, viloxazine has been shown to suppress auxiliary symptoms such as cataplexy and also abnormal sleep-onset REMref|narcolepsy_1 without really improving daytime somnolence.ref|narcolepsy_2

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.ref|alcoholism

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.ref|dysthymia

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.ref|viloxazine_serotonin Unlike any of the other drugs tested, it did not exhibit any anticholinergic effects.ref|viloxazine_anti-anticholinergic

It is also known to up-regulate GABA_B receptors in the frontal cortex.ref|gaba-frontal-cortex

ide 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,ref|biam2 (there were three cases worldwide, and most animal studies (and clinical trials that included epilepsy patients) indicated the presence of "anti"convulsant properties, so is not completely contraindicated in epilepsyref|seizure_risk), and increased libido.ref|Chebili_et_al_1998

Drug interactions

Viloxazine is known to increase plasma levels of phenytoin by an average of 37%.ref|phenytoin It is also known to significantly increase plasma levels of theophylline and decrease its clearance from the body,ref|theophylline_1 sometimes resulting in accidental overdose of theophylline.ref|theophylline_2

References

# cite web | url=http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=180462 | title=SID 180462-- PubChem Substance Summary | accessdate=5 November | accessyear=2005
# cite web | url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=mesh&dopt=Full&list_uids=68014745 | title=MEDLINE subject headings for Viloxazine | accessdate=5 November | accessyear=2005
# Biam (1999) VILOXAZINE CHLORHYDRATE, "MORPHOLINES" [online] Available from: http://www.biam2.org/www/Sub3399.html Accessed on 5 November 2005. (French)
# cite journal | author=Case DE, Reeves PR | title=The disposition and metabolism of I.C.I. 58,834 (viloxazine) in humans | journal=Xenobiotica | volume=5 | issue=2 | year=1975 | pages=113–29 | pmid=1154799 [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&list_uids=1154799&dopt=ExternalLink&ExternalLink=libs List of Library Holdings Worldwide]
# cite journal | author=Bouchard JM, Strub N, Nil R | title=Citalopram and viloxazine in the treatment of depression by means of slow drop infusion. A double-blind comparative trial | journal=Journal of Affective Disorders | volume=46 | issue=1 | year=1997 | pages=51–8 | pmid=9387086 | doi=10.1016/S0165-0327(97)00078-5 [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&list_uids=9387086&dopt=ExternalLink Fulltext options] [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&list_uids=9387086&dopt=ExternalLink&ExternalLink=libs List of Library Holdings Worldwide]
# [http://life7.2ch.net/test/read.cgi/utu/1075695229/ 【合法】個人輸入代行薬【未認可】] (The relevant section is English)
# 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
# cite journal | author=Danchev ND, Rozhanets VV, Zhmurenko LA, Glozman OM, Zagorevskii VA | title= [Behavioral and radioreceptor analysis of viloxazine stereoisomers] | journal=Biulleten' Eksperimental'noi Biologii i Meditsiny | volume=97 | issue=5 | year=1984 | pages=576–8 [Article in Russian] PMID 6326891 [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&list_uids=6326891&dopt=ExternalLink&ExternalLink=libs List of Library Holdings Worldwide]
# Biam (1999) "see" Biam, 1999.
# cite web | author=AstraZeneca Slovensko | year=2000 | url=http://www.astrazeneca.sk/produkt/cns/VIVALAN.asp | title=VIVALAN tbl obd | accessdate=2005-11-05
# cite web | author=AstraZeneca International | year=2003 | url=http://www.astrazeneca.com/productbrowse/4_78.aspx | title=Vivalan (viloxazine hydrochloride) | accessdate=2005-11-06
# cite journal | author=Attenburrow AA, Stanley TV, Holland RP | title=Nocturnal enuresis: a study | journal=The Practitioner | volume=228 | issue=1387 | year=1984 | pages=99–102 | pmid=6364124 [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&list_uids=6364124&dopt=ExternalLink&ExternalLink=libs List of Library Holdings Worldwide]
# cite journal | author=Yurdakok M, Kinik E, Guvenc H, Beduk Y | title=Viloxazine versus imipramine in the treatment of enuresis | journal= The Turkish Journal of Pediatrics | volume=29 | issue=4 | year=1987 | pages=227–30 | pmid=3332732 [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&list_uids=3332732&dopt=ExternalLink&ExternalLink=libs List of Library Holdings Worldwide]
# cite journal | author=Libert MH | title= [The use of viloxazine in the treatment of primary enuresis] | journal= Acta Urologica Belgica | volume=58 | issue=1 | year=1990 | pages=117–22 [Article in French] PMID 2371930 [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&list_uids=2371930&dopt=ExternalLink&ExternalLink=libs List of Library Holdings Worldwide]
# cite journal | author=Guilleminault C, Mancuso J, Salva MA, Hayes B, Mitler M, Poirier G, Montplaisir J | title=Viloxazine hydrochloride in narcolepsy: a preliminary report | journal=Sleep | volume=9 | issue=1 Pt 2 | year=1986 | pages=275–9 | pmid=3704453 [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&list_uids=3704453&dopt=ExternalLink&ExternalLink=libs List of Library Holdings Worldwide]
# cite journal | author=Mitler MM, Hajdukovic R, Erman M, Koziol JA | title=Narcolepsy | journal=Journal of Clinical Neurophysiology | volume=7 | issue=1 | year=1990 | pages=93–118 | pmid=1968069 | doi=10.1097/00004691-199001000-00008 [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&list_uids=1968069&dopt=ExternalLink&ExternalLink=libs List of Library Holdings Worldwide]
# cite journal | author=Altamura AC, Mauri MC, Girardi T, Panetta B | title=Alcoholism and depression: a placebo controlled study with viloxazine | journal=International journal of clinical pharmacology research | volume=10 | issue=5 | year=1990 | pages=293–8 | pmid=2079386 [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&list_uids=2079386&dopt=ExternalLink&ExternalLink=libs List of Library Holdings Worldwide]
# cite journal | author=Leon CA, Vigoya J, Conde S, Campo G, Castrillon E, Leon A | title= [Comparison of the effect of amisulpride and viloxazine in the treatment of dysthymia] | journal=Acta Psiquiatrica y Psicologica de America Latina | volume=40 | issue=1 | year=1994 | pages=41–9 [Article in Spanish] PMID 8053353 [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&list_uids=8053353&dopt=ExternalLink&ExternalLink=libs List of Library Holdings Worldwide]
# cite journal | author=Lippman W, Pugsley TA. | title=Effects of viloxazine, an antidepressant agent, on biogenic amine uptake mechanisms and related activities | journal=Canadian Journal of Physiology and Pharmacology | volume=54 | issue=4 | year=1976 | pages=494–509 | pmid=974878 [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&list_uids=974878&dopt=ExternalLink&ExternalLink=libs List of Library Holdings Worldwide]
# "see" Lippman and Pugsley, 1976.
# cite journal | author=Lloyd KG, Thuret F, Pilc A | title=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=Journal of Pharmacology & Experimental Therapeutics | volume=235 | issue=1 | year=1985 | pages=191–9 | pmid=2995646 [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&list_uids=2995646&dopt=ExternalLink&ExternalLink=libs List of Library Holdings Worldwide]
# "see" Biam, 1999.
# cite journal | author=Edwards JG, Glen-Bott M | title=Does viloxazine have epileptogenic properties? | journal=Journal of Neurology, Neurosurgery, and Psychiatry | volume=47 | issue=9 | year=1984 | pages=960–4 | pmid=6434699 [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&list_uids=6434699&dopt=ExternalLink&ExternalLink=libs List of Library Holdings Worldwide]
# cite journal | author=Chebili S, Abaoub A, Mezouane B, Le Goff JF | title= [Antidepressants and sexual stimulation: the correlation] | journal=L'Encephale | volume=24 | issue=3 | year=1998 | pages=180–4 [Article in French] PMID 9696909 [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&list_uids=9696909&dopt=ExternalLink&ExternalLink=libs List of Library Holdings Worldwide]
# cite journal | author=F Pisani, A Fazio, C Artesi, M Russo, R Trio, G Oteri, E Perucca and R Di Perri | title=Elevation of plasma phenytoin by viloxazine in epileptic patients: a clinically significant drug interaction | journal=Journal of Neurology, Neurosurgery, and Psychiatry | volume=55 | issue=2 | year=1992 | pages=126–127 | pmid=1538217 [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&list_uids=1538217&dopt=ExternalLink&ExternalLink=libs List of Library Holdings Worldwide]
# cite journal | author=Perault MC, Griesemann E, Bouquet S, Lavoisy J, Vandel B | title=A study of the interaction of viloxazine with theophylline | journal=Therapeutic Drug Monitoring | volume=11 | issue=5 | year=1989 | pages=520–2 | pmid=2815226 [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&list_uids=2815226&dopt=ExternalLink&ExternalLink=libs List of Library Holdings Worldwide]
# cite journal | author=Laaban JP, Dupeyron JP, Lafay M, Sofeir M, Rochemaure J, Fabiani P | title=Theophylline intoxication following viloxazine induced decrease in clearance | journal=European Journal of Clinical Pharmacology | volume=30 | issue=3 | year=1986 | pages=351–3 | pmid=3732375 | doi=10.1007/BF00541543 [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&list_uids=3732375&dopt=ExternalLink&ExternalLink=libs List of Library Holdings Worldwide]