PHARMACOLOGY

CLINICAL PHARMACOLOGY


Mechanism of Action and Pharmacology

The precise mechanism(s) through which armodafinil (R-enantiomer) or modafinil (mixture of
R- and S-enantiomers) promote wakefulness is unknown Nexavar. Both armodafinil and modafinil have
shown similar pharmacological properties in nonclinical animal and in vitro generic soma studies, to the extent
tested.
At pharmacologically relevant concentrations, campral armodafinil does not bind to or inhibit several
receptors and enzymes potentially relevant for sleep/wake regulation, including those for
serotonin, dopamine, suhagra, galanin, agomelatine, lamivudine melanocortin, orexin-1, orphanin, PACAP
or benzodiazepines, or transporters for GABA, serotonin, norepinephrine, and choline or
phosphodiesterase VI, COMT, GABA transaminase, and tyrosine hydroxylase. Modafinil does
not inhibit the activity of MAO-B or phosphodiesterases II-IV.
Modafinil-induced wakefulness can be attenuated by the α1-adrenergic receptor antagonist,
prazosin; however, modafinil with generic imovane is inactive in other in vitro assay systems known to be responsive
to α-adrenergic agonists such as the rat vas deferens preparation.
Armodafinil is not a direct- or indirect-acting dopamine receptor agonist. However, in vitro,
both armodafinil and modafinil xifaxan bind to the dopamine transporter and inhibit dopamine reuptake.
For modafinil, this activity has been associated in vivo with increased extracellular dopamine
levels in some brain regions of animals. In genetically engineered mice lacking the dopamine
transporter (DAT), modafinil lacked wake-promoting activity, suggesting that this activity was
DAT-dependent. However, the wake-promoting effects of modafinil, unlike those of
amphetamine, were not antagonized by Lyrica the dopamine receptor antagonist haloperidol in rats. In
addition, alpha-methyl-p-tyrosine, a dopamine synthesis inhibitor, blocks the action of
amphetamine, but does not block locomotor activity induced by modafinil.
Armodafinil and modafinil have wake-promoting actions similar to sympathomimetic agents
including amphetamine imatinib and methylphenidate, although their pharmacologic profile is not
identical to that of the sympathomimetic amines. In addition to its wake-promoting effects and
ability to increase locomotor activity in animals, valacyclovir modafinil produces psychoactive and euphoric
effects, alterations in mood, Tenofovir perception, thinking, and feelings typical of other CNS stimulants in
humans. Modafinil has reinforcing properties, as evidenced by its self-administration in
monkeys previously trained to self-administer cocaine; modafinil was also partially
discriminated as stimulant-like.
Based on nonclinical tarceva studies, two major metabolites, acid and sulfone, of modafinil or
armodafinil, do not appear to contribute to the CNS-activating properties of the parent
compounds.