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Dihydropyridine compounds and compositions for headaches

A kind of technology of dihydropyridine and compound, applied in the field of dihydropyridine compound and composition for headache

Inactive Publication Date: 2009-08-19
EISIA R&D MANAGEMENT CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Headache can be primary or secondary

Method used

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  • Dihydropyridine compounds and compositions for headaches
  • Dihydropyridine compounds and compositions for headaches
  • Dihydropyridine compounds and compositions for headaches

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0181] Anti-migraine agents are commonly evaluated using the carrageenan-induced thermal hyperalgesia model (Bingham et al., Experimental Neurology, 167:65-73 (2001); Daher et al., Life Sciences, 76:2349-2359 (2005)) . Antimigraine properties of compound A (i.e., 3-(2-cyanophenyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one) in response to thermal hyperalgesia Evaluated in the following rat carrageenan-induced inflammatory pain model.

[0182] Male Wistar rats (5 / group) were used in the experiments. The withdrawal latencies of both hind paws of rats to avoid thermal noxious stimuli were measured using TAIL FLICK 7360 (Ugo Basile, Italy). 1% carrageenan was injected into the sole of the right hind paw of the rat. 2 hours after carrageenan injection, rats were orally administered 3-(2-cyanophenyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridine-2 - ketone or vehicle. The withdrawal latencies of the two hind paws of the heat-stimulated rats were measured at 1, 3 and 5 hours a...

Embodiment 2

[0186] To evaluate the efficacy and For safety, a randomized double-blind placebo-controlled, multicenter parallel group study was conducted.

[0187] The primary efficacy endpoint was to evaluate the effect of 23-(2-cyanophenyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one hydrate in reducing migraine , based on the compound's change in frequency of migraine sessions per 28 days during treatment relative to baseline. A migraine period was defined as the onset, end, or recurrence of migraine within 24 hours. If the migraine lasted longer than 24 hours, it was considered a new migraine period.

[0188] The second objective of this study was to evaluate the role of 23-(2-cyanophenyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one hydrate in migraine Safety and tolerability in patients; characterizing 3-(2-cyanophenyl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one hydrate in Pharmacokinetics in a patient population; determination of plasma concentrations of 3-(2-cyanoph...

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Abstract

The invention provides methods for treating and / or preventing cognitive impairments, dementia, or neurodegenerative diseases and disorders (e.g., Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis) in patients by administering therapeutically effective amounts of an AMPA receptor antagonist (e.g., 1,2-dihydropyridine compounds) and therapeutically effective amounts of nootropics (e.g., cholinesterase inhibitors) to patients. The invention also provides combinations, commercial packages, and pharmaceutical compositions comprising therapeutically effective amounts of AMPA receptor antagonists (e.g., 1,2- dihydropyridine compounds) and therapeutically effective amounts nootropics (e.g., cholinesterase inhibitors). The 1,2-dihydropyridine compound may be, for example, 3- (2-cyanophenyl)-5-(2-pyridyl)-l-phenyl-l,2-dihydropyridin-2-one. The cholinesterase inhibitor may be, for example, donepezil.

Description

[0001] related application [0002] This application claims priority under 35 U.S.C. §119 to U.S. Provisional Application No. 60 / 689,519, filed June 13, 2005, and U.S. Provisional Application No. 60 / 667,665, filed April 4, 2005, which are hereby incorporated The entire contents are incorporated by reference. field of invention [0003] The present invention provides pharmaceutical compositions containing dihydropyridine compounds and methods of using the dihydropyridine compounds in the treatment of various diseases and disorders. The dihydropyridine compounds may optionally be used in combination with other drugs used in the treatment of various diseases and disorders, such as cholinesterase inhibitors or anti-migraine agents. Background of the invention [0004] The pathophysiology of migraine has been described in detail. See Waeber et al., Neurology, 61 (Suppl 4): S9-S20 (2003). Although the mechanism causing migraine is still not fully understood, neurological theori...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A01N43/40A61K31/44
Inventor 苏珊·阿布-谢克拉朱利安·A·格雷山西嘉晴森信行
Owner EISIA R&D MANAGEMENT CO LTD
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