CP-101,606: An NR2B-selective NMDA receptor antagonist

CNS Drug Reviews

Volumn 4, Issue 4, 1998, Pages 307-322

  Menniti, Frank S ^a   Shah, Ajit K ^a   Williams, Stephen A ^a   Wilner, Keith D ^a   White, W Frost ^a   Chenard, Bertrand L ^a  

^a PFIZER INC   (United States)

Author keywords

Alzheimer's disease; CP 101,606; Excitotoxicity; Glutamate; Head trauma; NMDA receptor antagonists; NMDA receptors; Parkinson's disease; Stroke

Indexed keywords

N METHYL DEXTRO ASPARTIC ACID RECEPTOR BLOCKING AGENT; TRAXOPRODIL;

ALZHEIMER DISEASE; AMINO ACID METABOLISM; ANIMAL EXPERIMENT; ANIMAL MODEL; BRAIN ISCHEMIA; CENTRAL NERVOUS SYSTEM; CONTROLLED STUDY; DRUG EFFECT; HEAD INJURY; NERVE DEGENERATION; NEUROPROTECTION; NEUROTRANSMITTER RELEASE; NONHUMAN; PARKINSON DISEASE; PRESYNAPTIC INHIBITION; RAT; REVIEW; SPREADING CORTICAL DEPRESSION; STROKE;

EID: 0032418317     PISSN: 1080563X     EISSN: None     Source Type: Journal    
DOI: 10.1111/j.1527-3458.1998.tb00073.x     Document Type: Review

References (69)

1. Albin RL, Greenamyre JT. Alternative excitotoxic hypothesis. Neurology 1992;42:733-737.
2. Barnard EA. Ionotropic glutamate receptors - New types and new concepts. Trends Pharmacol Sci 1991;18:141-148.
3. Bederson JB, Pitts LH, Tsuji M, Nishimura MC, Davis RL, Bartkowski H. Rat middle cerebral artery occlusion: Evaluation of the model and development of a neurologic examination. Stroke 1986;17:472-476.
4. Belluardo N, Mudo G, Dell'Albani P, Jiang XH, Condorelli DF. NMDA receptor-dependent and -independent immediate early gene expression induced by focal mechanical brain injury. Neurochem Int 1995;26:443-453.
5. Brimecombe JC, Boeckman FA, Aizenman E. Functional consequences of NR2 subunit composition in single recombinant N-methyl-D-aspartate receptors. Proc Natl Acad Sci USA 1997;94:11019-11024.
6. Brimecombe JC, Gallagher MJ, Lynch DR, Aizenman E. An NR2B point mutation affecting haloperidol and CP-101,606 sensitivity of single recombinant N-methyl-D-aspartate receptors. J Pharmacol Exp Ther 1998;286:627-634.
7. Bullock R, Kuroda Y, Teasdale GM, McCulloch J. Prevention of post-traumatic excitotoxic brain damage with NMDA antagonist drugs: A new strategy for the nineties. Acta Neurochir 1992;55:49-55.
8. Bullock R, Merchant RE, Carmack CA, et al. An open-label study, CP-101,606 in subjects with severe traumatic brain injury or spontaneous intracerebral hemorrhage. J Neurotrauma 1997;14:765.
9. Bullock R, Teasdale GM. Surgical management of traumatic intracranial hematomas. In: Braakman R, ed. Handbook of clinical neurology. Amsterdam: Elsevier, 1990:249-297.
10. Bullock R, Zauner A, Myseros JS, Marmarou A, Woodward JJ, Young HF. Evidence for prolonged release of excitatory amino acids in severe human head trauma. Relationship to clinical events. Ann New York Acad Sci 1995;765:290-297.
11. Bullock R, Zauner A, Woodward J, Young HF. Massive persistent release of excitatory amino acids following human occlusive stroke. Stroke 1995;26:2187-2189.
12. Chazot PL, Coleman SK, Cik M, Stephenson FA. Molecular characterization of N-methyl-D-aspartate receptors expressed in mammalian cells yields evidence for the coexistence of three subunit types within a discrete receptor molecule. J Biol Chem 1994;269:24403-24409.
13. Chenard BL, Bordner J, Butler TW, et al. (1S,2S)-1-(4-hydroxyphenyl)-2-(4-hydroxy-4-phenylpiperidino)-1-propanol: A potent new neuroprotectant which blocks N-methyl-D-aspartate responses. J Med Chem 1995;38:3138-3145.
14. Choi DW. Ionic dependence of glutamate neurotoxicity. J Neurosci 1987;7:369-379.
15. Choi DW. Glutamate neurotoxicity and diseases of the nervous system. Neuron 1988;1:623-634.
16. Choi DW, Koh JY, Peters S. Pharmacology of glutamate neurotoxicity in cortical cell culture: Attenuation by NMDA antagonists. J Neurosci 1988;8:185-196.
17. Christensen T, Jorgensen MB, Diemer NH. Impairment of fos protein formation in the rat infarct borderzone by MK-801, but not by NBQX. Acta Neurol Scand 1993;87:510-515.
18. Di X, Bullock R, Watson J, et al. Effect of CP-101,606, a novel NR2B-subunit antagonist of the N-methyl-D-aspartate receptor, on the volume of ischemic brain damage and cytotoxic brain edema after middle cerebral artery occlusion in the feline brain. Stroke 1997;28:2244-2251.
19. Gallagher MJ, Huang H, Grant ER, Lynch DR. The NR2B-speciftc interactions of polyamines and protons with the N-methyl-D-aspartate receptor. J Biol Chem 1997;272:2497-24979.
20. Goldman H, Hodgson V, Morehead M, Hazlett J, Murphy S. Cerebrovascular changes in a rat model of moderate closed-head injury. J Neurotrauma 1991;8:129-144.
21. Gorman AM, Scott MP, Rumsby PC, Meredith C, Griffiths R. Excitatory amino acid-induced cytotoxicity in primary cultures of mouse cerebellar granule cells correlates with elevated, sustained c-fos proto-oncogene expression. Neurosci Lett 1995;191:116-120.
22. Greenamyre JT. The role of glutamate in neurotransmission and in neurologic disease. Arch Neurol 1986;43:1058-1063.
23. Greene JG, Greenamyre JT. Bioenergetics and glutamate excitotoxicity. Prog Neurobiol 1996;48;613-634.
24. Griffiths R, Malcolm C, Ritchie L, et al. Association of c-fos mRNA expression and excitotoxicity in primary. cultures of mouse neocortical and cerebellar neurons. J Neurosci Res 1997;48:533-542.
25. Grotta J. Why do all drugs work in animals but none in stroke patients? 2. Neuroprotective therapy. J Int Med 1995;237:89-94.
26. Herrera DG, Maysinger D, Gadient R, Boeckh C, Otten U, Cuello AC. Spreading depression induces c-fos-like immunoreactivity and NGF mRNA in the rat cerebral cortex. Brain Res 1993;602:99-103.
27. Islam N, Aftabuddin M, Moriwaki A, Hori Y. Induction of N-methyl-D-aspartate receptor-mediated c-fos protein in the rat brain by incomplete ischaemia. Indian J Med Res 1994;100:281-288.
28. Jacobs O, Van Bree L, Mailleux P, et al. Homolateral cerebrocortical increase of immediate early gene and neurotransmitter messenger rnas after minimal cortical lesion: Blockade by N-methyl-D-aspartate antagonist. Neuroscience 1994;59:827-836.
29. Johnson JW, Ascher P. Glycine potentiates the NMDA response in cultured mouse brain neurons. Nature 1987;325:529-531.
30. Kemp JA, Leeson PD. The glycine site of the NMDA receptor - five years on. Trends Pharmacol Sci 1993;14:20-25.
31. Kinouchi H, Sharp FR, Chan PH, et al. MK-801 inhibits the induction of immediate early genes in cerebral cortex, thalamus, and hippocampus, but not in substantia nigra, following middle cerebral artery occlusion. Neurosci Lett 1994;179:111-114.
32. Kleckner NW, Dingledine R. Requirement for glycine in activation of NMDA receptors expressed in Xenopus oocytes. Science 1988;241:835-837.
33. Koizumi J, Yoshida Y, Nakazawa T, Ooneda G. Experimental studies of ischemic brain edema. I. A new experimental model of cerebral embolism in rats in which recirculation can be introduced in the ischemic area. Jpn J Stroke 1986;8:1-8.
34. Kutsuwada T, Kashiwabuchi N, Mori H, et al. Molecular diversity of the NMDA receptor channel. Nature 1992;358:36-41.
35. Luo JH, Wang YH, Yasuda RP, Dunah AW, Wolfe BB. The majority of N-methyl-D-aspartate-receptor complexes in adult rat cerebral cortex contain at least three different subunits (NR1/NR2A/NR2B). Mol Pharmacol 1997;51:79-86.
36. Maragos WF, Greenamyre JT, Penney JB, Young AB. Glutamate dysfunction in Alzheimer's disease: an hypothesis. Trends Neurosci 1987;10:65-68.
37. Mattson MP. Excitatory amino acids, growth factors, and calcium: A teeter-totter model for neural plasticity and degeneration. In: BeN-Ari Y, ed. Excitatory amino acids and neuronal plasticity. New York: Plenum Press, 1990;211-220.
38. Mayer ML, Westbrook GL. The physiology of excitatory amino acids in the vertebrate nervous system. Prog Neurobiol 1987;28:197-276.
39. McCulloch J. Glutamate receptor antagonists in cerebral ischaemia. J Neural Transm 1994;71-79.
40. McIntosh TK, Smith DH, Meaney DF, Kotapka MJ, Gennarelli TA, Graham DI. Neuropathological sequelae of traumatic brain injury: Relationship to neurochemical and biomechanical mechanisms. Lab Invest 1996;74:315-342.
41. Meldrum BS, Garthwaite J. Excitatory amino acid neurotoxicity and neurodegenerative disease. Trends Pharmacol Sci 1990;11:379-387.
42. Menniti F, Chenard B, Collins M, Ducat M, Shalaby I, White F. CP-101,606, a potent neuroprotectant selective for forebrain neurons. Eur J Pharmacol 1997;331:117-126.
43. Menniti FS, Pagnozzi MJ, Butler P, Chenard BL, Jaw-Tsai SS, White WF. CP-101,606, an NR2B-subunit selective NMDA receptor antagonist, inhibits NMDA and injury induced c-fos expression and cortical spreading depression in rodents. Eur J Pharmacol 1998 (submitted).
44. Merchant RE, Bullock R, Carmack CA, Shah A, Wilner K, Ko G. An double-blind placebo-controlled trial of CP-101,606 in patients with mild or moderate traumatic brain injury. J Neurotrauma 1997;14:764.
45. Meredith C, Scott M, Rumsby P, et al. Sustained c-fos expression is associated with excitotoxicity during the development of neuronal cells in vitro. Biochem Soc Trans 1996;24:6S-60.
46. Miller JD, Bullock R, Graham DI, Chen MH, Teasdale GM. Ischemic brain damage in a model of acute subdural hematoma. Neurosurgery 1990;27:433-439.
47. Monyer H, Sprengel R, Schoepfer R, et al. Heteromeric NMDA receptors: Molecular and functional distinction of subtypes. Science 1992;256:1217-1221.
48. Mori H, Mishina M. Structure and function of the NMDA-receptor channel. Neuropharmacology 1995;34:1219-1237.
49. Mott DD, Zhang S, Washburn MS, Fendley M, Dingledine R. CP-101,606 antagonizes NMDA receptors by interacting with the polyamine modulatory site. Soc Neurosci Abstr 1996;22 (Suppl):1-3.
50. Muir KW, Lees KR. Clinical experience with excitatory amino acid antagonist drugs. Stroke 1995;26:503-513.
51. Nellgard B, Weiloch T. NMDA-receptor blockers but not NBQX, an AMPA-receptor antagonist, inhibit spreading depression in the rat brain. Acta Physiol Scand 1992;146:497-503.
52. Obrenovitch TP, Zilkha E. Inhibition of cortical spreading depression by L-701,324, a novel antagonist at the glycine site of the N-methyl-D-aspartate-receptor complex. Br J Pharmacol 1996;117:931-937.
53. Okiyama K, Smith DH, White WF, McIntosh TK. Effects of the NMDA antagonist CP-98,113 on regional cerebral edema and cardiovascular, cognitive, and neurobehavioral function following experimental brain injury in the rat. Brain Res 1998;792:291-298.
54. Okiyama K, Smith DH, White WF, Richter K, McIntosh TK. Effects of the novel NMDA antagonists CP-98,113; CP-101,581; and CP-101,606 on cognitive function and regional cerebral edema following experimental brain injury in the rat. J Neurotrauma 1997;14:211-222.
55. Olney JW, Labruyere J, Wang G, Wozniak DF, Price MT, Sesma MA. NMDA antagonist neurotoxicity: Mechanism and prevention. Science 1991;254:1515-1518.
56. Pagnozzi MJ, Chambers LK, Menniti FS, Chenard BL, White WF. CP-101,606, a potent and selective antagonist of forebrain NMDA receptors: In vivo neuroprotective activity. Soc Neurosci Abst 1995;21 (Suppl):1-3.
57. Rosenberg PA, Aizenman E. Hundred-fold increase in neuronal vulnerability to glutamate toxicity in astrocyte-poor cultures of rat cerebral cortex. Neurosci Lett 1989:103:162-168.
58. Rothman SM, Olney JW. Excitotoxicity and the NMDA Receptor. Trends Neurosci 1987;10:299-302.
59. Rowley M, Kulagowski JJ, Watt AP, et al. Effect of plasma protein binding on in vivo activity and brain penetration of glycine/NMDA-receptor antagonists. J Med Chem 1997;40:4053-4068.
60. Schmidt WJ. Behavioural effects of NMDA-receptor antagonists. J Neural Transm 1994;43:63-69.
61. Shan Y, Carlock LR, Walker PD. NMDA-receptor overstimulation triggers a prolonged wave of immediate early gene expression: Relationship to excitotoxicity. Exp Neurol 1997;144:406-415.
62. Sheng M, Cummings J, Roldan LA, Jan YN, Jan LY. Changing subunit composition of heteromeric NMDA receptors during development of rat cortex. Nature 1994;368:144-147.
63. Siesjo BK. Calcium-mediated processes in neuronal degeneration. Ann NY Acad Sci 1994;747:140-161.
64. Szatkowski M, Attwell D. Triggering and execution of neuronal death in brain ischemia: Two phases of glutamate release by different mechanisms. Trends Neurosci 1994;17:359-365.
65. Takano K, Latour LL, Formato JE, et al. The role of spreading depression in focal ischemia evaluated by diffusion mapping. Ann Neurol 1996;39:308-318.
66. Traynelis SF, Hartley M, Heinemann SF. Control of proton sensitivity of the NMDA receptor by RNA splicing and polyamines. Science 1995:268:873-876.
67. Tsuchida E, Rice M, Bullock R. The neuroprotective effect of the forebrain-selective NMDA antagonist CP-101,606 upon focal ischemic brain damage caused by acute subdural hematoma in the rat. J Neurotrauma 1997;14:409-417.
68. Williams K. Pharmacological properties of recombinant N-methyl-D-aspartate (NMDA) receptors containing the epsilon 4 (NR2D) subunit. Neurosci Lett 1995;184:181-184.
69. Williams K, Russell SL, Shen YM, Molinoff PB. Developmental switch in the expression of NMDA receptors occurs in vivo and in vitro. Neuron 1993;10:267-278.