C - Chemistry – Metallurgy – 12 – Q
Patent
C - Chemistry, Metallurgy
12
Q
C12Q 1/68 (2006.01) A01N 43/04 (2006.01) A61K 31/00 (2006.01) A61K 31/07 (2006.01) A61K 31/4168 (2006.01) A61K 31/485 (2006.01) A61K 31/4965 (2006.01) A61K 31/505 (2006.01) A61K 31/53 (2006.01) A61K 31/55 (2006.01) A61K 45/06 (2006.01) A61K 49/00 (2006.01) C07H 21/04 (2006.01) G01N 33/68 (2006.01)
Patent
CA 2449934
Markedly enhanced activity of pacemaker (hyperpolarization-activated, cation- nonselective, HCN) ion channels governs spontaneous firing in sensory cells of allodynic rats. An HCN ion channel specific blocker, ZD7288, dose-dependently and completely suppresses allodynia. Nerve injury increases the population of large DRG neurons expressing a high density of Ih and modulates HCN mRNA expression. New methods of treating pain by targeting HCN pacemaker channels are developed. In addition, new methods for identifying compositions useful for treating pain are disclosed.
L'invention a trait à une amélioration sensible de l'activité des canaux ioniques de stimulation cardiaque (à activation par hyperpolarisation, à non sélectivité de cations, HCN), ladite activité régissant la décharge spontanée dans les cellules sensorielles de rats allodyniques. Un bloqueur spécifique de canaux ioniques HCN, le ZD7288, supprime l'allodynie de manière proportionnelle à la dose administrée et de manière totale. Les lésions nerveuses augmentent la population de grands neurones DRG présentant une densité importante de I¿h ?et module l'expression d'ARNm HCN. L'invention concerne de nouveaux procédés de traitement de la douleur par ciblage des canaux de stimulation cardiaque HCN. Elle concerne également de nouveaux procédés d'identification de compositions utiles au traitement de la douleur.
Brown Sean
Chaplan Sandra
Dubin Adrienne
Guo Hong-Qing
Lee Doo Hyun
Norton Rose Or S.e.n.c.r.l. S.r.l./llp
Ortho-Mcneil Pharmaceutical Inc.
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