Abstract：
:In the present study, we investigated the possibility that MK-801 (dizocilpine), a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, owes its potent neuroprotective properties to calcium channel blocking ability rather than to its NMDA receptor antagonism. Rat hippocampal slices were exposed to a long hypoxic period (20 min) from which only 13.8% recovered their neuronal function after 30 min of reoxygenation. The recovery rate of neuronal function from 20-min hypoxia was increased to 100% when slices were pretreated with 5 microM MK-801. DL-2-amino-5-phosphonovalerate (APV), a competitive NMDA receptor antagonist, even at relatively high concentration (100 microM), provided only marginal protection against such severe hypoxic insult. The L-type calcium channel blocker diltiazem (DILT) was more effective than APV in protecting hypoxic slices against neuronal damage. Combining suboptimal concentrations of DILT and MK-801 produced a neuroprotective effect with significantly exceeded the calculated additive effect of the two drugs. Such synergism could not be demonstrated between DILT and APV, a combination that produced only the expected additive neuroprotective effect. The observed synergy between the calcium channel blocker (DILT) and MK-801, along with other studies that demonstrated interaction between these two drugs, led us to postulate that MK-801 possesses calcium channel blocking properties through which its neuroprotective effect is exerted. These calcium channels could either be of the L-type or otherwise, channels which are being activated only under stressful conditions, such as hypoxia or ischemia.
journal_name
Brain Resjournal_title
Brain researchauthors
Schurr A,Payne RS,Rigor BMdoi
10.1016/0006-8993(95)00466-4subject
Has Abstractpub_date
1995-07-03 00:00:00pages
233-6issue
2eissn
0006-8993issn
1872-6240pii
0006-8993(95)00466-4journal_volume
684pub_type
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