Definition
ChEBI: A 2-[(diphenylmethyl)sulfinyl]acetamide that has R configuration at the sulfur atom. Like its racemate, modafinil, it is used for the treatment of sleeping disorders such as narcolepsy, obstructive sleep apnoea, and shift-work sleep disord
r. Peak concentration in the blood later occurs later following administration than with modafinil, so it is thought that armodafinil may be more effective than modafinil in treating people with excessive daytime sleepiness.
Description
Armodafinil, an α1-adrenoceptor agonist, was launched for the
oral treatment of excessive sleepiness associated with narcolepsy, SWSD, and
obstructive sleep apnea/hypopnea syndrome (OSA). It is the R-enantiomer
of modafinil, which is a previously marketed wake-promoting agent. The key
differentiator for armodafinil is its longer pharmacokinetic half-life as
compared with the S-enantiomer (10-14 hvs.3-4h). At therapeutic
concentrations, armodafinil does not bind to most of the potentially
relevant receptors for sleep/wake regulation (e.g., serotonin, dopamine,
and adenosine receptors) or transporters of neurotransmitters or enzymes
involved in sleep/wake regulation (e.g., serotonin, norepinephrine, and
phosphodiesterase VI transporters). Both armodafinil and modafinil block
dopamine reuptake by binding to the dopamine transporter and increasing
dopamine concentrations in certain regions of the brain. However, dopamine
receptor antagonists (e.g., haloperidol) and dopamine synthesis inhibitors
(e.g., α-methyl-p-tyrosine) do not block modafinil’s action.
In addition to its wake-promoting effects and ability to increase locomotor activity in animals, modafinil produces psychoactive and euphoric effects, alterations in mood, perception, thinking, and feelings typical of other CNS stimulants in humans. Modafinil was also partially discriminated as stimulant-like. However, the potential for abuse and dependency appears to be lower for modafinil than amphetamine-like stimulants.The most common adverse
events associated with armodafinil included headache, nausea, dizziness,
and insomnia.
Synthesis
Armodafinil can be obtained starting from (+)-2(
diphenylmethylsulfinyl)acetic acid via optical resolution using S-(-)-amethylbenzylamine,
followed by esterification to the methyl ester and
subsequent amidation with ammonium hydroxide. It can also be derived
enantioselectively from 2-(diphenylmethylthio)acetamide via asymmetric
oxidation with cumene hydroperoxide and titanium isopropoxide-S,Sdiethyl
tartrate complex.
