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Exclusively from Sigma-RBI
Prod. No. C 4238
Cerebral ischemia causes the release of excessive amounts of the excitatory amino acid glutamic acid (Prod. No. G5667), resulting in the toxic activation of several types of glutamate receptors, including the ionotropic N-methyl-D-aspartate (NMDA) and a-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) receptors, which leads to necrotic neuronal cell death. Glutamic acid antagonism can ameliorate the neuronal injury associated with cerebral ischemia. Specifically antagonizing the calcium-conducting channels associated with NMDA receptors on neurons can block the calcium influx mediated by glutamatic acid [1]. Known ligands for the NMDA receptor ion channel site include phencyclidine (PCP, Prod. No. P3029) and MK-801 (Prod. No. M-107), both of which act as non-competitive blockers [2].
Sigma-RBI introduces CNS-1102 (Aptiganel hydrochloride, Prod. No.
C4238), a selective, non-competitive NMDA receptor antagonist that was rationally designed to interact with the NMDA receptor ion channel binding site while minimizing s receptor cross-reactivity common to similar ligands like PCP [3]. Abandoned in the clinic due to intolerable psychotomimetic side-effects, CNS-1102 is poised to be an extremely useful tool in the search
for more therapeutically suitable NMDA receptor antagonists.
Studies with CNS-1102 have demonstrated:
- Reduced early postischemic injury and improved perfusion following middle
cerebral artery occlusion in rats, an animal model for stroke [4,5].
- Neuroprotective effects on the cortical and caudoputaminal regions during the initial
3 hours of ischemia (when administered 15 minutes postocculsion). Postmortem tissue
analysis showed a 66% reduction in infarcted tissue as compared with untreated animals [4,5].
- A neuroprotective effect on cerebral white matter, which could prove useful in
understanding and treating white matter ischemic changes common to elderly patients [6].
Manufactured and sold under exclusive license from CeNeS Limited.
References:
- Lees, K.R., Neurology, 49(5 Suppl 4), S66-69 (1997).
- Weiloch, T., Science, 230, 681-683 (1985).
- Reddy, N.L., et al., J. Med. Chem., 37, 260-267 (1994).
- Minematsu, K., et al., Neurology, 43, 397-403 (1993).
- Minematsu, K., et al., Stroke, 24, 2074-2081 (1993).
- Schäbitz, W.-R., et al., Stroke, 31, 1709-1714 (2000).
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