| 17658512 |
Dayanithi G, Desmadryl G, Travo C, Chabbert C, Sans A: Trimetazidine modulates AMPA/kainate receptors in rat vestibular ganglion neurons. Eur J Pharmacol. 2007 Nov 21;574(1):8-14. Epub 2007 Jul 10.
Trimetazidine (1 [2,3,4-trimethoxy-benzyl] piperazine, 2 HCl) is an anti-ischemic agent frequently administered as a prophylactic treatment for episodes of angina pectoris and chorioretinal disturbances. It is also employed as a symptomatic treatment of vertigo but its mechanism of action is yet to be defined. Using Fura-2 fluorescence photometry and whole-cell patch-clamp recordings we investigated the effect of trimetazidine on the [Ca (2+)](i) and current responses induced by the application of non-N-methyl-D-aspartate (NMDA) receptor agonists on low density vestibular ganglion neuronal cultures explanted from 3 day s postnatal rats. Trimetazidine blocked the [Ca (2+)](i) and current responses induced by 100 microM applications of both kainate and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA). These responses were dependent on external Ca (2+) and were blocked by the voltage-dependent Ca (2+) channel blockers Ni (2+) and Cd (2+) . Trimetazidine only acts on the AMPA/kainate receptors and had no effect on K (+)-induced depolarizations. Dose-dependent curves were obtained for the inhibition by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and trimetazidine (IC (50) 7 microM and 0.7 microM) of kainate stimulations. After AMPA stimulation, dose-response inhibition curves showed an IC (50) of 3 microM for CNQX and 25 microM for trimetazidine. These results indicate that trimetazidine could be a potent antagonist of AMPA/kainate receptors in vestibular ganglion neurons. This may explain the protective role of trimetazidine in the inner ear suggesting an anti-excitotoxic activity. |
1(0,0,0,1) |