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{{Drugbox|
{{Drugbox
|IUPAC_name = 2-benzhydrylsulfinylethanehydroxamic acid
| Verifiedfields = changed
| image=Adrafinil-structure.png
| verifiedrevid = 477243010
| CAS_number=63547-13-7
| IUPAC_name = (''RS'')-2-benzhydrylsulfinylethanehydroxamic acid
| ATC_prefix=N06
| image =Adrafinil.png 
| ATC_suffix=BX17
 
| ATC_supplemental=
<!--Clinical data-->
| PubChem=3033226
| tradename = 
| DrugBank=
| Drugs.com = {{drugs.com|international|adrafinil}}
| chemical_formula =  
| pregnancy_category = 
| legal_AU = S4
| legal_status = Unscheduled ([[United States|US]])
| routes_of_administration = Oral
 
<!--Pharmacokinetic data-->
| bioavailability = 80%
| metabolism = 75% Hepatic,  Cyp?
| elimination_half-life = 1 hour
| excretion = [[Renal]]
 
<!--Identifiers-->
| CAS_number_Ref = {{cascite|changed|??}}
| CAS_number = 63547-13-7
| ATC_prefix = N06
| ATC_suffix = BX17
| PubChem = 3033226
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 2297976
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = BI81Z4542G
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D07348
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 93077
| synonyms = CRL-40028
 
<!--Chemical data-->
| C=15 | H=15 | N=1 | O=3 | S=1
| molecular_weight = 289.351 g/mol
| molecular_weight = 289.351 g/mol
| bioavailability=  
| smiles = O=S(C(c1ccccc1)c2ccccc2)CC(=O)NO
| metabolism =  
| InChI = 1/C15H15NO3S/c17-14(16-18)11-20(19)15(12-7-3-1-4-8-12)13-9-5-2-6-10-13/h1-10,15,18H,11H2,(H,16,17)
| elimination_half-life=
| InChIKey = CGNMLOKEMNBUAI-UHFFFAOYAN
| excretion =
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| pregnancy_category =  
| StdInChI = 1S/C15H15NO3S/c17-14(16-18)11-20(19)15(12-7-3-1-4-8-12)13-9-5-2-6-10-13/h1-10,15,18H,11H2,(H,16,17)
| legal_status =  
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| routes_of_administration= Oral
| StdInChIKey = CGNMLOKEMNBUAI-UHFFFAOYSA-N
}}
}}
'''Adrafinil''' is a mild [[central nervous system]] [[stimulant]] drug used to relieve excessive [[sleep|sleepiness]] and inattention in [[elderly]] patients. It is also used [[off-label]] by individuals wishing to avoid [[Fatigue (physical)|fatigue]], such as night workers or others who need to stay awake and alert for long periods of time.
__Notoc__
{{SI}}
{{CMG}}


Adrafinil is a [[prodrug]]; it is primarily [[metabolize]]d ''[[in vivo]]'' to [[modafinil]] (''Provigil''®), resulting in nearly identical [[pharmacology|pharmacological]] effects. Unlike modafinil, however, it takes time for the metabolite to accumulate to active levels in the bloodstream. Effects usually are apparent within 45-60 minutes when taken orally on an empty [[stomach]].
==Overview==


Adrafinil, also known by the codename CRL 40028, has as its chemical name 2-(Diphenylmethyl) sulfinyl acetohydroxamic acid. Its molecular formula is C<sub>15</sub>H<sub>15</sub>NO<sub>3</sub>S. The drug's molecular weight is 289.4 daltons.
'''Adrafinil''' ('''Olmifon''') is a [[wakefulness-promoting agent]] (or ''eugeroic'') used to relieve excessive [[somnolence|sleepiness]] and inattention. It is also used [[off-label]] by individuals wishing to avoid [[fatigue (physical)|fatigue]], such as [[shift work|night workers]] or others who need to stay awake and alert for long periods of time.


Adrafinil does not currently have [[Food and Drug Administration|FDA]] approval in the [[United States]], although it is used in [[France]] and elsewhere in [[Europe]]. The drug is marketed by the American [[pharmaceutical]] company Cephalon, which acquired Group Lafon in 2001, under the brand name ''Olmifon''.
Adrafinil is a [[prodrug]]; it is primarily [[metabolize]]d ''[[in vivo]]'' to [[modafinil]], resulting in nearly identical [[pharmacology|pharmacological]] effects. Unlike modafinil, however, it takes time for the [[metabolite]] to accumulate to active levels in the bloodstream. Effects usually are apparent within 45–60 minutes when taken orally on an empty [[stomach]].
 
Adrafinil does not currently have [[Food and Drug Administration|FDA]] approval and is thus unregulated in the [[United States]]. It was marketed in [[France]] and elsewhere in [[Europe]] under the trade name '''Olmifon''' until September 2011 when France's FDA-equivalent reassessed the drug and withdrew marketing permission, citing known adverse reactions and an unsatisfactory risk to benefit ratio.


==History==
==History==
Adrafinil was discovered in the late 1970s by scientists working with the French pharmaceutical company Group Lafon. The drug was first offered as an experimental treatment for [[narcolepsy]] in France in 1986. Later on, Lafon scientists developed modafinil as a stand-alone drug because the latter drug was understood to be a more highly selective alpha-1 adrenergic and also featured less in the way of side effects such as stomach pain, skin irritations, feelings of tension, and an increase in liver enzyme levels.
Adrafinil was discovered in the late 1970s by scientists working with the French pharmaceutical company [[Group Lafon]]. First offered in France in 1986 as an experimental treatment for [[narcolepsy]], Lafon later developed [[modafinil]], the primary metabolite of adrafinil. Even though the exact [[mechanism of action]] is unclear, "most investigators assume that adrafinil and modafinil both serve as [[alpha-1 adrenergic receptor|α<sub>1</sub>-adrenergic receptor]] [[agonist]]s."<ref name="Milgram2014">{{cite journal|last1=Milgram|first1=Norton|title=Adrafinil: A Novel Vigilance Promoting Agent|journal=http://onlinelibrary.wiley.com/doi/10.1111/j.1527-3458.1999.tb00100.x/pdf|date=1999|volume=5|issue=3|page=193|url=http://onlinelibrary.wiley.com/doi/10.1111/j.1527-3458.1999.tb00100.x/pdf|accessdate=2 October 2014}}</ref> The evidence in support of this hypothesis is, however, weak and other mechanisms of action are probable.<ref name="Milgram2014" /> Modafinil possesses greater selective α<sub>1</sub>-adrenergic activity than adrafinil, without many of adrafinil's common [[side effect]]s (stomach pain, skin irritation, anxiety and (with prolonged use) elevated [[liver function tests|liver enzymes]]).<ref name=Ballas>{{cite journal|last=Ballas|first=Christos A|author2=Deborah Kim|author3=Claudia F Baldassano|author4=Nicholas Hoeh|title=Modafinil: past, present and future|journal=Expert Review of Neurotherapeutics|date=July 2002|volume=2|issue=4|pages=449–57|doi=10.1586/14737175.2.4.449|pmid=19810941}}</ref> This makes it important to monitor the liver of an individual using adrafinil for prolonged periods.
 
As of September 2011, [[Cephalon]] has discontinued '''Olmifon''', its adrafinil product.
 
==Legal status==
==Legal status==
Adrafinil and its close relative [[modafinil]] were added to the list of prohibited substances according to [[World Anti-Doping Agency]] in 2004.<ref>[http://www.wada-ama.org/rtecontent/document/2007_List_En.pdf World Anti-Doping Agency - 2007 prohibited list]</ref>  
===Athletic doping===
Adrafinil and its [[active metabolite]] modafinil were added to the list of substances prohibited for athletic competition according to [[World Anti-Doping Agency]] in 2004.<ref>[http://www.wada-ama.org/rtecontent/document/2007_List_En.pdf ''World Anti-Doping Agency - 2007 Prohibited List'']</ref>
 
===United States===
In the United States, adrafinil is {{As of|2013|alt=currently}} unregulated. It has not been approved for any clinical uses by the U.S. [[Food and Drug Administration]]. Unlike modafinil, adrafinil is not classified as a controlled substance and does not fall under [[Drug Enforcement Administration|DEA]] jurisdiction; in particular, it is not illegal to possess without a prescription and can be imported privately by citizens.


In United States, adrafinil is [[As of 2007|currently]] unregulated. It has not been approved for any clinical uses by the U.S. [[Food and Drug Administration]]. As such, it can't be legally sold or introduced into interstate commerce. Unlike modafinil, adrafinil is not yet classified as a controlled substance and does not fall under [[Drug Enforcement Agency|DEA]] jurisdiction; particularly, it is not illegal to possess without a prescription and can be imported privately by citizens{{Fact|date=July 2007}}.
===Canada===
In [[Canada]] adrafinil is unregulated and can be legally purchased within the country as a [[research chemical]], or imported privately by citizens.


==Trivia==
===New Zealand===
The metabolites of Adrafinil (as well as Modafinil) contain sulfur, and can easily be detected by a peculiar odour of the urine of the person who has taken it.{{Fact|date=February 2007}}
In 2005 a Medical Classification Committee in [[New Zealand]] recommended to [http://www.medsafe.govt.nz/index.asp MEDSAFE NZ] that adrafinil be classified as a prescription medicine.  


==References==
"Adrafinil had been referred to the MCC for classification as a prescription medicine by the Medicines Control section of Medsafe following growing concern about increased imports and potential abuse of this substance as a party drug. Evidence of misuse was supplied in support of the request for classification.
{{reflist|2}}
 
Adrafinil is not scheduled in New Zealand but is chemically related to modafinil which is a prescription medicine taken orally for mental function impairment in the elderly.


* {{cite web | url=http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=184744 | title=SID 184744 -- PubChem Substance Summary | work=The PubChem Project | publisher=National Center for Biotechnology Information | accessmonthday=7 December | accessyear=2005}}
All participants agreed that adrafinil should be classified as a prescription medicine."<ref>[http://www.medsafe.govt.nz/profs/class/mccMinDec2005.htm MCC Minutes Out of Session Meeting]. Medsafe.govt.nz (2013-05-23). Retrieved on 2013-12-18.</ref>


==See also==
==See also==
*[[Modafinil]]
* [[Ampakine]]
*[[Ampakines]]
* [[Armodafinil]]
 
==References==
{{Reflist|2}}


==External links==
==External links==
*[http://www.nevapress.com/cnsdr/full/5/3/193.pdf ''Adrafinil: A Novel Vigilance Promoting Agent'' by Norton W. Milgram, Heather Callahan, and Christina Siwak of the University of Toronto at Scarborough, CNS Drug Reviews, Vol. 5, No. 3, pp. 193-212] (PDF)
* {{cite web | url=http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=184744 | title=''SID 184744 - PubChem Substance Summary'' | work=PubChem Project | publisher=National Center for Biotechnology Information | accessdate=7 December 2005}}
* [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15300665&dopt=Abstract ''Adrafinil-induced orofacial dyskinesia.'' by Thobois S, Xie J, Mollion H, Benatru I, Broussolle E. of the Department of Neurology, The Pierre Wertheimer Neurological Hospital, Lyon, France]
* {{cite web | url=http://www2.biam2.org/www/Sub1545.html | title=''Adrafinil - Bank of Automated Data on Drugs'' | work=Bank of Automated Data on Drugs | publisher=VIDAL | accessdate=4 October 2008| archiveurl= http://web.archive.org/web/20081005032946/http://www.biam2.org/www/Sub1545.html| archivedate= 5 October 2008 <!--DASHBot-->| deadurl= no}}
* {{Cite journal | last1 = Milgram | first1 = Norton W. | last2 = Callahan | first2 = Heather | last3 = Siwak | first3 = Christina | doi = 10.1111/j.1527-3458.1999.tb00100.x | title = Adrafinil: A Novel Vigilance Promoting Agent | journal = CNS Drug Reviews | volume = 5 | issue = 3 | pages = 193–212 | date = September 1992 | url = http://onlinelibrary.wiley.com/doi/10.1111/j.1527-3458.1999.tb00100.x/pdf | format = PDF}} {{open access}}
* {{Cite journal | last1 = Thobois | first1 = S. P. | last2 = Xie | first2 = J. | last3 = Mollion | first3 = H. | last4 = Benatru | first4 = I. | last5 = Broussolle | first5 = E. | title = Adrafinil-induced orofacial dyskinesia | doi = 10.1002/mds.20154 | journal = Movement Disorders | volume = 19 | issue = 8 | pages = 965–966 | date = August 2004| pmid = 15300665}}
 
 
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Latest revision as of 17:15, 18 August 2015

Adrafinil
Clinical data
SynonymsCRL-40028
AHFS/Drugs.comInternational Drug Names
Routes of
administration		Oral
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • Unscheduled (US)
Pharmacokinetic data
Bioavailability80%
Metabolism75% Hepatic, Cyp?
Elimination half-life1 hour
ExcretionRenal
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEMBL
E number{{#property:P628}}
ECHA InfoCard{{#property:P2566}}Lua error in Module:EditAtWikidata at line 36: attempt to index field 'wikibase' (a nil value).
Chemical and physical data
FormulaC15H15NO3S
Molar mass289.351 g/mol
3D model (JSmol)
 ☒N☑Y (what is this?)  (verify)

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Adrafinil (Olmifon) is a wakefulness-promoting agent (or eugeroic) used to relieve excessive sleepiness and inattention. It is also used off-label by individuals wishing to avoid fatigue, such as night workers or others who need to stay awake and alert for long periods of time.

Adrafinil is a prodrug; it is primarily metabolized in vivo to modafinil, resulting in nearly identical pharmacological effects. Unlike modafinil, however, it takes time for the metabolite to accumulate to active levels in the bloodstream. Effects usually are apparent within 45–60 minutes when taken orally on an empty stomach.

Adrafinil does not currently have FDA approval and is thus unregulated in the United States. It was marketed in France and elsewhere in Europe under the trade name Olmifon until September 2011 when France's FDA-equivalent reassessed the drug and withdrew marketing permission, citing known adverse reactions and an unsatisfactory risk to benefit ratio.

History

Adrafinil was discovered in the late 1970s by scientists working with the French pharmaceutical company Group Lafon. First offered in France in 1986 as an experimental treatment for narcolepsy, Lafon later developed modafinil, the primary metabolite of adrafinil. Even though the exact mechanism of action is unclear, "most investigators assume that adrafinil and modafinil both serve as α1-adrenergic receptor agonists."[1] The evidence in support of this hypothesis is, however, weak and other mechanisms of action are probable.[1] Modafinil possesses greater selective α1-adrenergic activity than adrafinil, without many of adrafinil's common side effects (stomach pain, skin irritation, anxiety and (with prolonged use) elevated liver enzymes).[2] This makes it important to monitor the liver of an individual using adrafinil for prolonged periods.

As of September 2011, Cephalon has discontinued Olmifon, its adrafinil product.

Legal status

Athletic doping

Adrafinil and its active metabolite modafinil were added to the list of substances prohibited for athletic competition according to World Anti-Doping Agency in 2004.[3]

United States

In the United States, adrafinil is currently unregulated. It has not been approved for any clinical uses by the U.S. Food and Drug Administration. Unlike modafinil, adrafinil is not classified as a controlled substance and does not fall under DEA jurisdiction; in particular, it is not illegal to possess without a prescription and can be imported privately by citizens.

Canada

In Canada adrafinil is unregulated and can be legally purchased within the country as a research chemical, or imported privately by citizens.

New Zealand

In 2005 a Medical Classification Committee in New Zealand recommended to MEDSAFE NZ that adrafinil be classified as a prescription medicine.

"Adrafinil had been referred to the MCC for classification as a prescription medicine by the Medicines Control section of Medsafe following growing concern about increased imports and potential abuse of this substance as a party drug. Evidence of misuse was supplied in support of the request for classification.

Adrafinil is not scheduled in New Zealand but is chemically related to modafinil which is a prescription medicine taken orally for mental function impairment in the elderly.

All participants agreed that adrafinil should be classified as a prescription medicine."[4]

See also

References

  1. ↑ 1.0 1.1 Milgram, Norton (1999). "Adrafinil: A Novel Vigilance Promoting Agent". http://onlinelibrary.wiley.com/doi/10.1111/j.1527-3458.1999.tb00100.x/pdf. 5 (3): 193. Retrieved 2 October 2014. External link in |journal= (help)
  2. ↑ Ballas, Christos A; Deborah Kim; Claudia F Baldassano; Nicholas Hoeh (July 2002). "Modafinil: past, present and future". Expert Review of Neurotherapeutics. 2 (4): 449–57. doi:10.1586/14737175.2.4.449. PMID 19810941.
  3. ↑ World Anti-Doping Agency - 2007 Prohibited List
  4. ↑ MCC Minutes Out of Session Meeting. Medsafe.govt.nz (2013-05-23). Retrieved on 2013-12-18.

External links


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