Synthesis and structure-activity relationships of 6,7-benzomorphan derivatives as use-dependent sodium channel blockers for the treatment of stroke

Journal of Medicinal Chemistry

Volumn 45, Issue 17, 2002, Pages 3755-3764

  Grauert, Matthias ^a   Bechtel, Wolf D ^a   Weiser, Thomas ^a   Stransky, Werner ^a   Nar, Herbert ^a   Carter, Adrian J ^a  

^a BOEHRINGER INGELHEIM PHARMA GMBH AND CO KG   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

1,2,3,4,5,6 HEXAHYDRO 6,11,11 TRIMETHYL 3 [2 (PHENYLMETHOXY)PROPYL] 2,6 METHANO 3 BENZAZOCIN 10 OL; 6,7 BENZOMORPHAN DERIVATIVE; BATRACHOTOXIN; BIII 890 CL; DEXTROMETHORPHAN; GLUTAMIC ACID; LIFARIZINE; LUBELUZOLE; MEXILETINE; SIPATRIGINE; SODIUM CHANNEL; SODIUM CHANNEL BLOCKING AGENT; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ANTICONVULSANT ACTIVITY; ARTICLE; BINDING AFFINITY; BRAIN SLICE; CONVULSION; DRUG BINDING SITE; DRUG POTENCY; DRUG SYNTHESIS; ELECTRIC SHOCK; MOUSE; NEUROTRANSMITTER RELEASE; NONHUMAN; RAT; STEREOCHEMISTRY; STROKE; STRUCTURE ACTIVITY RELATION;

ANIMALS; BENZOMORPHANS; CEREBRAL CORTEX; CEREBROVASCULAR ACCIDENT; CORPUS STRIATUM; CRYSTALLOGRAPHY, X-RAY; ELECTROSHOCK; GLUTAMIC ACID; MALE; MICE; NEUROPROTECTIVE AGENTS; RADIOLIGAND ASSAY; RATS; SEIZURES; SODIUM CHANNEL BLOCKERS; STRUCTURE-ACTIVITY RELATIONSHIP; THROMBOEMBOLISM; VERATRIDINE;

EID: 0037103266     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm020875j     Document Type: Article

References (55)

1. Normal and abnormal calcium homeostasis in neurons: A basis for the pathophysiology of traumatic and ischemic central nervous system injury
2. Nonvesicular release of glutamate from glial cells by reversed electrogenic glutamate uptake
3. 2+ exchanger
4. Anoxic and ischemic injury of myelinated axons in CNS white matter: From mechanistic concepts to therapeutics
5. Sodium channels and therapy of central nervous system diseases
6. + channels as targets for neuroprotective drugs
7. + channels: A rational and effective strategy against ischemic brain damage
8. The sodium channel from rat brain
9. Structure and function of voltage-sensitive ion channels
10. + channels: Local anesthetics, antiarrhythmics and anticonvulsants
11. Neurotoxins that act on voltage-sensitive sodium channels in excitable membranes
12. Cellular and molecular biology of voltage-gated sodium channels
13. Structure and function of voltage-gated ion channels
14. Primary structure and functional expression of the α1 subunit of the rat brain sodium channel
15. Structure and function of the β2 subunit of brain sodium channels, a transmembrane glycoprotein with a CAM motif
16. The glial voltage-gated sodium channel: Cell- and tissue-specific mRNA expression
17. Primary structure of rat brain sodium channel III deduced from the cDNA sequence
18. Existence of distinct sodium channel messenger RNAs in rat brain
19. A novel, abundant sodium channel expressed in neurons and glia
20. Brain and heart sodium channel subtype mRNA expression in rat cerebral cortex
21. Cellular and molecular biology of voltage-gated sodium channels
22. The saxitoxin/tetrodotoxin binding site on cloned rat brain Iia Na channels is in the transmembrane electric field
23. + ionophore by neurotoxins. An allosteric model
24. Binding of batrachotoxin A 20-α-benzoate to a receptor site associated with sodium channels in synaptic nerve ending particles
25. Batrachotoxin: Chemistry and pharmaclogy
26. + channels resistant to batrachotoxin
27. Interaction of batrachotoxin with the local anesthetic receptor site in transmembrane segment IVS6 of the voltage-gated sodium channel
28. Neuroprotective effects of a use-dependent blocker of voltage-dependent sodium channels, BW619C89, in rat middle cerebral artery occlusion
29. BW619C89, a glutamate release inhibitor, protects against focal cerebral ischemic damage
30. Ischemic brain damage: Reduction by sodium-calcium ion channel modulator RS-87476
31. Reduction by lifarizine of the neuronal damage induced by cerebral ischaemia in rodents
32. Neuroprotective profile of lifarizine (RS-87476) in rat cerebrocortical neurones in culture
33. Neuroprotective efficacy of lifarizine (RS-87476) in a simplified rat survival model of 2 vessel occlusion
34. Combined neuroprotection and reperfusion therapy for stroke. Effect of lubeluzole and Diaspirin cross-linked hemoglobin in experimental focal ischemia
35. Lubeluzole protects sensorimotor function and reduces infarct size in a photochemical stroke model in rats
36. Protection with lubeluzole against delayed ischemic brain damage in rats
37. The effects of lifarizine in acute cerebral infarction: A pilot safety study
38. The importance of voltage-dependent sodium channels in cerebral ischaemia
39. Dextromethorphan blocks N-methyl-D-aspartate-induced currents and voltage-operated inward currents in cultured cortical neurons
40. Dextromethorphan: Cellular effects reducing neuronal hyperactivity
41. Synthesis and structure-activity relationships of 6,7-benzomorphan derivatives as antagonists of the NMDA receptor-channel complex
42. Potent blockade of sodium channels and protection of brain tissue from ischemia by BIII 890 CL
43. A revived target for drug development? Glutamate in CNS disorders
44. Ion channels involved in stroke
45. 2+ exchanger
46. N-methyl-D-aspartate receptor channel block by the enantiomeric 6,7-benzomorphans BIII 277 CL and BIII 281 CL
47. Changes in cortical amino acids during electrical kindling in rats
48. Reduction of glutamate release and protection against ischemic brain damage by BW 1003C87
49. Determination of gutamate and aspartate in microdialysis samples by reversed-phase column liquid chromatography with fluorescence and electrochemical detection
50. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding
51. BIIR 561 CL: A novel combined antagonist of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors and voltage-dependent sodium channels with anticonvulsive and neuroprotective properties