IDRA 21, a positive allosteric modulator of the glutamate AMPA receptor, produced a concentration-dependent inhibition of glutamate-induced inactivation of membrane currents in recombinant HEK 293 (human embryonic kidney) cells stably transfected with human GluR1/2 flip receptors. Oral administration of IDRA 21 produced a highly significant improvement in the performance of a delayed matching-to-sample (DMTS) task by young adult rhesus monkeys. The pattern of task improvement over the dose range 0.15 - 10 mg/kg was maintained to 48 hr after the single dose administration[1]. IDRA-21 reduces alpha-amino-3-hydroxy-5-methylisoxazolepropionic acid (AMPA) receptors desensitisation in vitro and restores learning and cognitive impairment in vivo. In cerebellar granule cells (CGCs) in culture IDRA-21 reduces NMDAR whole-cell currents. IDRA-21 shortens miniature excitatory postsynaptic currents mediated by NMDARs (NMDA-mEPSCs) in CGCs grown in low potassium with no effect on peak amplitudes[2]. IDRA 21 and cyclothiazide potentiate KA-evoked (kainic acid) current in a dose dependent way, being cyclothiazide more potent but less efficacious than IDRA 21. Conversely IDRA 5 acts as a negative modulator of KA evoked-current[3].
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