Biological Activity
cp-465022 is an ampa antagonist.the inhibition of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (ampa) receptor has been hypothesized to lead to neuroprotective efficacy after cerebral ischemia on the basis of the activity in ischemia models of a variety of compounds with varying selectivity for ampa over other glutamate receptor subtypes.
in vitro
cp-465022 inhibited ampa receptor-mediated currents in rat cortical neurons and such inhibition was found to be noncompetitive with agonist concentration. cp-465022 was selective for ampa over kainate and n-methyl-d-aspartate receptors. however, cp-465022 was found to be equipotent for ampa receptors composed of different ampa receptor subunit combinations, which indicated that cp-465022 is equivalently potent for inhibition of ampa receptor-mediated responses in different types of neurons expressing different ampa receptor subunits [1].
in vivo
animal study showed that cp-465022 could potently and efficaciously inhibit ampa receptor-mediated hippocampal synaptic transmission and the induction of seizures. however, at comparable doses, cp-465022 failed to prevent ca1 neuron loss after brief global ischemia or to reduce infarct volume after temporary middle cerebral artery occlusion [2].
References
[1] lazzaro jt, paternain av, lerma j, chenard bl, ewing fe, huang j, welch wm, ganong ah, menniti fs. functional characterization of cp-465,022, a selective, noncompetitive ampa receptor antagonist. neuropharmacology. 2002 feb;42(2):143-53.
[2] menniti fs, buchan am, chenard bl, critchett dj, ganong ah, guanowsky v, seymour pa, welch wm. cp-465,022, a selective noncompetitive ampa receptor antagonist, blocks ampa receptors but is not neuroprotective in vivo. stroke. 2003 jan;34(1):171-6.
