Migraine is a paroxysmal headache that lasts 4 to 72 hours, accompanied by nausea, vomiting, sensitivity to light, sensitivity to sound, or the like [The Merck Manual, Seventeenth Edition, Chapter 168; Therapeutic Guideline of The Japanese Society of Neurology; International Classification of Headache Disorders-II: ICHD-II, 2004]. Vasodilation in the extra- and/or intra-cranial vessels including the superficial temporal artery has been proposed as one of the pathophysiology of migraine and its pathogenesis [Arch. Neurol. Psychiatr., Vol. 39, p. 737-763 (1938); Cephalagia, Vol. 1, p. 143-147 (1981); Internal medicine, Vol. 81, p. 601-609 (1998); Internal Medicine, Vol. 81, p. 639 (1998)]. It has also been known that ergot alkaloid and sumatriptan, hydrophilic agonists of serotonin receptor 5-HT1 (5-hydroxytryptamine 1), that do not cross the blood-brain barrier are effective for the treatment of migraine, because these agonists act on the serotonin receptor 5-HT1 in the cerebral vascular smooth muscle to constrict the dilated blood vessels [Ann. N.Y. Acad. Sci., Vol. 600, p. 587-600 (1990); Neurology, Vol. 43, p. S43-S47 (1993)].
It is thus believed that migraine can be treated by suppressing vasodilation in the extra- and/or intra-cranial vessels. Concerning the cause of migraine onset, there have also been reports presenting theories based on neurogenic inflammation around the trigeminal nerve and cerebral blood vessel, or around the dura mater blood vessel, or based on activation of the central nerve such as in cortical spreading depression [Lancet, Vol. 363, p. 381-391 (2004)].
There are further reports concerning migraine (see Non-Patent Documents 1 to 3).
Some of the examples of therapeutic agents for migraine currently in use in the clinic include non-steroidal antiphlogistic analgetics such as triptans (for example, sumatriptan), and ibuprophens. As for the preventive agents, for example, antiepileptic agents such as topiramate, and calcium antagonist agents such as flunarizine are currently used in the clinic.
It is known that the adenosine concentration in the blood plasma of migraine patients an hour after a migraine attack increases by an average of 68% from that during the normal period, and that the activation of the adenosine A2 receptor by adenosine suppresses the serotonin uptake by platelets in a manner that depends on adenosine concentration, and causes vasodilation as a result of a rapid serotonin release [Can. J, Neurol. Sci., Vol. 2, p. 55-58 (1998)]. Further, intravenous administration of an adenosine enhancer to a migraine patient is known to induce a migraine attack [Med. J. Aust., Vol. 162, p. 389-390 (1995)]. It is also known that adenosine possesses a strong vasodilating action, and that the adenosine A2A receptor and the adenosine A2B receptor are involved in vasodilation during migraine and in adenosine-induced vasodilation [Am. J. Physiol. Heart Circ. Physiol., Vol. 280, p. 2329-2335 (2001)]. It is thus believed that migraine can be treated by suppressing adenosine-induced vasodilation.
Caffeine, which has a non-selective adenosine antagonistic activity, is known to relieve migraine; however, caffeine has side-effects, namely, psychiatrical dependence, and causes caffeine withdrawal headache [see Pain, 1991, Vol. 44, p. 151-155; Drugs, 1995, Vol. 49, p. 37-50]. Further, xanthine derivatives are known to be useful as therapeutic drugs for migraine (see Patent Document 1).
It is known that adenosine is distributed abundantly in the whole body, and exhibits a variety of physiological activities on the central nervous system, the cardiac muscle, the kidneys, the smooth muscle, and the like through its receptors (see Non-Patent Document 4).
For example, adenosine A1 antagonists are known to facilitate defecation (Jpn. J. Pharmacol., 1995, Vol. 68, p. 119). Further, involvement of the adenosine A2A receptor, particularly in the central nervous system is known. The antagonists of the adenosine A2A receptor are known to be useful as, for example, therapeutic drugs for Parkinson's disease (see Non-Patent Document 5), or therapeutic drugs for sleep disorder (see Nature Neuroscience, 2005, p. 1; Patent Document 2).
There are some reports concerning the relationship between adenosine receptors and migraine (see Non-Patent Documents 6 to 13).
For example, compounds represented by the following formulae (I), (II), (III), (IV), (V), (VI), and (VII) are known as compounds having a selective adenosine A2A receptor antagonistic activity (see Patent Documents 3 to 9, and Non-Patent Documents 14 and 15).

(wherein R1 represents methyl, ethyl, propyl, butyl, or 3-methylbutyl, or any of these groups substituted with hydroxy; R2 represents phenyl, pyridyl, pyrimidinyl, 5,6-dihydro-2H-pyridylmethyl, or tetrahydropyranyloxy, or any of these groups substituted with 1 to 3 substituents selected from a fluorine atom, a chlorine atom, a bromine atom, methyl, ethyl, methoxy, and ethoxy; R3 represents pyridyl or tetrahydropyranyl; R4 and R5 may be the same or different, and each represent a hydrogen atom, a fluorine atom, or 2-methoxyethoxy; and R6 represents methyl, ethyl, propyl, or butyl)