Sexual dimorphism of the catechol-O-methyltransferase gene in narcolepsy is associated with response to modafinil

被引：41

作者：

Dauvilliers Y. ^{[1
,2
]}

Neidhart E. ^{[2
]}

Billiard M. ^{[1
]}

Tafti M. ^{[2
]}

机构：

[1] Neurologie B, Hopital Gui-de-Chauliac, Montpellier

[2] Unité de Biochimie et Neurophysiologie Clinique, Département dePsychiatrie, Université de Genève

来源：

The Pharmacogenomics Journal | 2002年 / 2卷 / 1期

关键词：

Dopamine; Excessive daytime sleepiness; Gender; Sleep;

D O I：

10.1038/sj.tpj.6500088

中图分类号：

学科分类号：

摘要：

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.

引用

页码：65 / 68

页数：3

共 17 条

[1]

Nishino S., Mignot E., Pharmacological aspects of human and canine narcolepsy, Prog. Neurobiol, 52, pp. 27-78, (1997)

[2]

Dauvilliers Y., Neidhart E., Lecendreux M., Billiard M., Tafti M., MAO-A and COMT polymorphisms and gene effects in narcolepsy, Mol. Psychiatry, 6, pp. 367-372, (2001)

[3]

Bastuji H., Jouvet M., Successful treatment of idiopathic hypersomnia and narcolepsy with moclafinil, Prog. Neuropsychopharmacol. Biol. Psychiatry, 12, pp. 695-700, (1988)

[4]

Billiard M., Besset A., Montplaisir J., Laffont F., Goldenberg F., Weill J.S., Lubin S., Modafinil: A double-blind multicentric study, Sleep, 17, pp. S107-S112, (1994)

[5]

US Modafinil in Narcolepsy Multicenter Study Group, Ann. Neurol, 43, pp. 88-97, (1998)

[6]

Randomized trial of modafinil as a treatment for the excessive daytime somnolence of narcolepsy, Neurology, 54, pp. 1166-1175, (2000)

[7]

Lin J.S., Hou Y., Jouvet M., Potential brain neuronal targets for amphetamine-, methylphenidate-, and modafinil-induced wakefulness, evidenced by c-fos immunocytochemistry in the cat, Proc. Natl. Acad. Sci. U S A, 93, pp. 14128-14133, (1996)

[8]

Ferraro L., Antonelli T., Tanganelli S., O'Connor W.T., Perez de la Mora M., Mendez-Franco J., Et al., The vigilance promoting drug modafinil increases extracellular glutamate levels in the medial preoptic area and the posterior hypothalamus of the conscious rat: Prevention by local GABAA receptor blockade, Neuropsychopharmacology, 20, pp. 346-356, (1999)

[9]

Engber T.M., Dennis S.A., Jones B.E., Miller M.S., Contreras P.C., Brain regional substrates for the actions of the novel wake-promoting agent modafinil in the rat: Comparison with amphetamine, Neuroscience, 87, pp. 905-911, (1998)

[10]

Scammell T.E., Estabrooke I.V., McCarthy M.T., Chemelli R.M., Yanagisawa M., Miller M.S., Et al., Hypothalamic arousal regions are activated during modafinil-incluced wakefulness, J. Neurosci, 20, pp. 8620-8628, (2000)

← 1 2 →