Adrafinil, sold under the brand name Olmifon, is a wakefulness-promoting medication that was formerly used in France to improve alertness, attention, wakefulness, and mood, particularly in the elderly.
Adrafinil is a prodrug; it is primarily in vivo to modafinil, resulting in very similar pharmacology effects.
Adrafinil was marketed in France until September 2011 when it was voluntarily discontinued due to an unfavorable risk–benefit ratio.
Medical uses
Adrafinil is a wakefulness-promoting agent and was used to promote alertness, attention, wakefulness, and mood.
It was particularly used in the elderly.
Available forms
Adrafinil was available in the form of 300mg oral tablets.
Side effects
There is a
case report of two patients that adrafinil may increase interest in sex.
A case report of adrafinil-induced orofacial dyskinesia exists.
Pharmacology
Pharmacodynamics
Because α
1-adrenergic receptor antagonists were found to block effects of adrafinil and modafinil in animals, "most investigators assumed that adrafinil and modafinil both serve as α
1-adrenergic receptor agonists."
However, adrafinil and modafinil have not been found to bind to the α
1-adrenergic receptor and they lack peripheral
sympathomimetic associated with activation of this receptor;
hence, the evidence in support of this hypothesis is weak, and other mechanisms are probable.
Modafinil was subsequently screened at a variety of targets in 2009 and was found to act as a weak, atypical blocker of the dopamine transporter (and hence as a dopamine reuptake inhibitor), and this action may explain some or all of its pharmacological effects.
Relative to adrafinil, modafinil possesses greater specificity in its action, lacking or having a reduced incidence of many of the common side effects of the former (including
stomach pain,
skin irritation,
anxiety, and elevated
liver with prolonged use).
Pharmacokinetics
In addition to modafinil, adrafinil also produces
modafinil acid (CRL-40467) and modafinil sulfone (CRL-41056) as metabolites, which form from metabolic modification of modafinil.
Chemistry
Adrafinil is the
N-
hydroxyl group analogue of
modafinil and is also known as
N-hydroxymodafinil.
Analogues of adrafinil include modafinil, armodafinil, CRL-40,940, CRL-40,941, and fluorenol, among others.
History
Adrafinil was discovered in 1974 by two chemists working for the French pharmaceutical company Laboratoires Lafon who were screening compounds in search of
.
Pharmacological studies of adrafinil instead revealed
psychostimulant-like effects such as
hyperactivity and
wakefulness in animals.
The substance was first tested in humans, specifically for the treatment of narcolepsy, in 1977–1978.
Introduced by Lafon (now Cephalon), it reached the market in France in 1984,
and for the treatment of narcolepsy in 1985.
In 1976, two years after the discovery of adrafinil, its active metabolite modafinil was discovered.
Society and culture
Names
Adrafinil is the
generic term of the drug and its and .
It is also known by its brand name Olmifon and its developmental code name
CRL-40028.
Regulation
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.
Additive in United States dietary supplements
Adrafinil is sometimes included as an ingredient in misbranded or adulterated dietary supplements. One company had attempted to get a New Dietary Ingredient pre-market notification approved for adrafinil in 2017, but the Food and Drug Administration rejected
it:
A position that adrafinil is an unapproved drug was indicated in a warning letter
A position that adrafinil is an unapproved drug was also indicated by FDA in a press release regarding a criminal action
FDA indicated a position that adrafinil is an unapproved drug in later criminal action undertaken during 2022: “The also illegally sold multiple other unapproved and misbranded drugs, including adrafinil crystalline powder...”
Certain products, formulated with adrafinil in them, have been listed as subject to a May 2023 import alert by Food and Drug Administration because they are considered as containing an active pharmaceutical ingredient.
Adrafinil containing products, purporting to be dietary supplements, are not allowed for use by military service members. This is because the Department of Defense considers adrafinil an unapproved drug.
New Zealand
In 2005 a Medical Classification Committee in
New Zealand recommended to MEDSAFE NZ that adrafinil be classified as a prescription medicine due to risks of it being used as a
party drug. At that time adrafinil was not scheduled in New Zealand.
Research
In a
clinical trial with the tricyclic antidepressant
clomipramine and
placebo as comparators, adrafinil showed efficacy in the treatment of depression.
In contrast to clomipramine however, adrafinil was well-tolerated, and showed greater improvement in psychomotor retardation in comparison.
The authors concluded that further investigation of the potential antidepressant effects of adrafinil were warranted.
Further reading
External links
