Study of the Safety and Effectiveness of NXN-188 for the Acute Treatment of Migraine Attacks With Aura

Summary

The following study is being conducted to explore the safety and effectiveness of a new chemical entity called NXN-188 in subjects with a history of migraine with aura. In this study subjects will treat two attacks of migraine with aura during the aura phase - once with placebo and once with NXN-188.

Timeline

Start

2009-05

Primary completion

2010-03

Completion

2010-12

Publications

• Background Lassen LH, Christiansen I, Iversen HK, Jansen-Olesen I, Olesen J. The effect of nitric oxide synthase inhibition on histamine induced headache and arterial dilatation in migraineurs. Cephalalgia. 2003 Nov;23(9):877-86. doi: 10.1046/j.1468-2982.2003.00586.x.
• Background Afridi S, Kaube H, Goadsby PJ. Occipital activation in glyceryl trinitrate induced migraine with visual aura. J Neurol Neurosurg Psychiatry. 2005 Aug;76(8):1158-60. doi: 10.1136/jnnp.2004.050633.
• Background Alderton WK, Cooper CE, Knowles RG. Nitric oxide synthases: structure, function and inhibition. Biochem J. 2001 Aug 1;357(Pt 3):593-615. doi: 10.1042/0264-6021:3570593.
• Background Burstein R, Collins B, Jakubowski M. Defeating migraine pain with triptans: a race against the development of cutaneous allodynia. Ann Neurol. 2004 Jan;55(1):19-26. doi: 10.1002/ana.10786.
• Background Costa A, Smeraldi A, Tassorelli C, Greco R, Nappi G. Effects of acute and chronic restraint stress on nitroglycerin-induced hyperalgesia in rats. Neurosci Lett. 2005 Jul 22-29;383(1-2):7-11. doi: 10.1016/j.neulet.2005.03.026. Epub 2005 Apr 18.
• Background Handy RL, Moore PK. Effects of selective inhibitors of neuronal nitric oxide synthase on carrageenan-induced mechanical and thermal hyperalgesia. Neuropharmacology. 1998;37(1):37-43. doi: 10.1016/s0028-3908(97)00201-3.
• Background Heinzen EL, Pollack GM. Pharmacodynamics of morphine-induced neuronal nitric oxide production and antinociceptive tolerance development. Brain Res. 2004 Oct 15;1023(2):175-84. doi: 10.1016/j.brainres.2004.07.015.
• Background Inoue T, Mashimo T, Shibata M, Shibuta S, Yoshiya I. Rapid development of nitric oxide-induced hyperalgesia depends on an alternate to the cGMP-mediated pathway in the rat neuropathic pain model. Brain Res. 1998 May 11;792(2):263-70. doi: 10.1016/s0006-8993(98)00147-4.
• Background Levy D, Zochodne DW. NO pain: potential roles of nitric oxide in neuropathic pain. Pain Pract. 2004 Mar;4(1):11-8. doi: 10.1111/j.1533-2500.2004.04002.x.
• Background Martelletti P, D'Alo S, Stirparo G, Rinaldi C, Cifone MG, Giacovazzo M. Modulation of nitric oxide synthase by nitric oxide donor compounds in migraine. Int J Clin Lab Res. 1998;28(2):135-9. doi: 10.1007/s005990050033.
• Background Mungrue IN, Bredt DS, Stewart DJ, Husain M. From molecules to mammals: what's NOS got to do with it? Acta Physiol Scand. 2003 Oct;179(2):123-35. doi: 10.1046/j.1365-201X.2003.01182.x.
• Background Naik AK, Tandan SK, Kumar D, Dudhgaonkar SP. Nitric oxide and its modulators in chronic constriction injury-induced neuropathic pain in rats. Eur J Pharmacol. 2006 Jan 13;530(1-2):59-69. doi: 10.1016/j.ejphar.2005.11.029. Epub 2005 Dec 20.
• Background Osborne MG, Coderre TJ. Effects of intrathecal administration of nitric oxide synthase inhibitors on carrageenan-induced thermal hyperalgesia. Br J Pharmacol. 1999 Apr;126(8):1840-6. doi: 10.1038/sj.bjp.0702508.
• Background Shimomura T, Murakami F, Kotani K, Ikawa S, Kono S. Platelet nitric oxide metabolites in migraine. Cephalalgia. 1999 May;19(4):218-22. doi: 10.1046/j.1468-2982.1999.019004218.x.
• Background Taffi R, Vignini A, Lanciotti C, Luconi R, Nanetti L, Mazzanti L, Provinciali L, Silvestrini M, Bartolini M. Platelet membrane fluidity and peroxynitrite levels in migraine patients during headache-free periods. Cephalalgia. 2005 May;25(5):353-8. doi: 10.1111/j.1468-2982.2004.00863.x.
• Background Tfelt-Hansen P, De Vries P, Saxena PR. Triptans in migraine: a comparative review of pharmacology, pharmacokinetics and efficacy. Drugs. 2000 Dec;60(6):1259-87. doi: 10.2165/00003495-200060060-00003.
• Background Thomsen LL, Olesen J. Nitric oxide theory of migraine. Clin Neurosci. 1998;5(1):28-33.
• Background van der Kuy PH, Lohman JJ. The role of nitric oxide in vascular headache. Pharm World Sci. 2003 Aug;25(4):146-51. doi: 10.1023/a:1024800512790.
• Background Yoon YW, Sung B, Chung JM. Nitric oxide mediates behavioral signs of neuropathic pain in an experimental rat model. Neuroreport. 1998 Feb 16;9(3):367-72. doi: 10.1097/00001756-199802160-00002.

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