| 摘要 |
The present invention relates to the discovery of a novel molecular pathway involved in long-term hyperexcitability of sensory neurons, which, in higher animals, is associated with persistent pain. It is based on the discovery that, following injury to an axon of a neuron, an increase in nitric oxide synthase activity results in increased nitric oxide production, which, in turn, activates guanylyl cyclase, thereby increasing levels of cGMP. Increased cGMP results in activation of protein kinase G (“PKG”), which then is retrogradely transported along the axon to the neuron cell body, where it phosphorylates MAPKerk. |
| 主权项 |
1. A transdermal device containing an effective amount of an agent having formula I: wherein n is 1, 2 or 3; Z is N or CH; wherein X represents one of the following functional groups: wherein Y represents one of the following functional groups: wherein A represents aryl or heteroaryl groups un-substituted or substituted by one or more lower-alkyl, lower-alkoxy, hydroxy, alkoxy, amimo, alkylamino or halogen groups; wherein R is hydrogen, lower-alkyl, or amidino; wherein R1, R2, R4, R5 is independently hydrogen, hydroxyl, lower-alkoxy, amino, or halogen; and wherein R3 is alkyl, aryl, heteroaryl, alkoxy, aryloxy, or a group selected from the following: wherein R6-R10 are independently hydrogen, hydroxy, lower-alkyl, lower-alkoxy, halogen, trifluoromethyl, carboxy, alkoxycarbonyl, amino, alkylamino, alkylcarbonylamino, alkylsulfonylamino (e. g. CF3SO2NH—, CH3SO2NH—), and tetrazole. |
