Sexual dimorphism of the catechol-O-methyltransferase gene in narcolepsy is associated with response to modafinil.
The gene for catechol-O-methyltransferase (COMT) plays a key modulatory role in dopaminergic and noradrenergic neurotransmission. Recent evidence suggests that modafinil, like other stimulants, might act through the dopaminergic system. We have reported a sexual dimorphism and a strong effect of the COMT genotype on narcolepsy symptoms and hypothesized that response to modafinil treatment may be associated with the COMT genotype. Here we confirm that COMT genotype distribution between men and women narcoleptics is associated with response to modafinil. In addition, the optimal daily dose of modafinil is approximately 100 mg lower in women narcoleptics and lower in all narcoleptics with low activity COMT genotype. Our results suggest that a sexual dimorphism in COMT activity affects the response to modafinil and probably to other dopaminergic stimulants.
Dauvilliers
Y
Y
Neurologie B, Hĵpital Gui-de-Chauliac, Montpellier, France.
Neidhart
E
E
Billiard
M
M
Tafti
M
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001559:Benzhydryl Compounds / Q000627:therapeutic use*; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D000697:Central Nervous System Stimulants / Q000627:therapeutic use*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077408:Modafinil; D009290:Narcolepsy / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D012727:Sex Characteristics
D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D002394:Catechol O-Methyltransferase; D000077408:Modafinil