However, in vitro, modafinil binds to the dopamine transporter and inhibits dopamine reuptake. 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 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. In the cat, equal wakefulness-promoting doses of methylphenidate and amphetamine increased neuronal activation throughout the brain. Modafinil at an equivalent wakefulness-promoting dose selectively and prominently increased neuronal activation in more discrete regions of the brain.
The relationship of this finding in cats to the effects of modafinil in humans is unknown. 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 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. The optical enantiomers of modafinil have similar pharmacological actions in animals. Two major metabolites of modafinil, modafinil acid and modafinil sulfone, do not appear to contribute to the CNS-activating properties of modafinil.
Pharmacokinetics Modafinil is a 1: The enantiomers do not interconvert. At steady state, total exposure to R-modafinil is approximately three times that for S-modafinil. The effective elimination half-life of modafinil after multiple doses is about 15 hours.
Apparent steady states of total modafinil and R-modafinil are reached after days of dosing. Food has no effect on overall PROVIGIL bioavailability; however, time to reach peak concentration tmax may be delayed by approximately one hour if taken with food.
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Modafinil helped him to get out of this trouble and now he is one of the best students in the class. I am very happy for him Michel My husband told me to take Modafinil tablets as I abnormally feel very sleepy. So, we went to the doctor and consulted him. Finally, I was made to take the pills. Only after taking it I came to know about how good it feels to stay focused, active and alert Lisa After taking Modafinil, I found improvement in my condition.
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