Patent ID: 6399574
Filing Date: 2002-06-04
Classification: A61K,C07K

Abstract:
A method for treating or preventing disorders in which the pathophysiology involves excessive excitation of nerve cells by excitatory amino acids or agonists of the NMDA receptor which comprises administering to a patient in need thereof a therapeutically effective amount of an active agent selected from the group consisting of (i) conantokin S1 the amino acid sequence Gly-Asp-Xaa1-Xaa1-Tyr-Ser-Lys-Phe-Ile-Xaa2-Arg-Glu-Arg-Xaa2-Ala-Gly-Arg-Leu-Asp-Leu-Ser-Lys-Phe-Pro (SEQ ID NO:5) wherein Xaa1 and Xaa2 is &ggr;-carboxyglutamic acid, (ii) a conantokin peptide chimera which contains a first, second, third and fourth domain, wherein said first domain is GE&ggr;&ggr; (SEQ ID NO:12) and GD&ggr;&ggr; (SEQ ID NO:27), said second domain is selected from the group consisting of LQ&ggr;NQ&ggr; (SEQ ID NO:13), YQKML&ggr; (SEQ ID NO:15), VAKMAA&ggr; (SEQ ID NO:18), LQANQA (SEQ ID NO:22), LQANQ&ggr; (SEQ ID NO:24 ), LQSNQ&ggr; (SEQ ID NO:25), LQTNQ&ggr; (SEQ ID NO:26), YSKFI&ggr; (SEQ ID NO:28) and YRKAMA&ggr; (SEQ ID NO:31), said third domain is selected from the group consisting of NLR&ggr; (SEQ ID NO:16), LAR&ggr; (SEQ ID NO:19), LIRA (SEQ ID NO:23), LIR&ggr; (SEQ ID NO:14), RER&ggr; (SEQ ID NO:29) and LEAKKAQ&ggr; (SEQ ID NO:32), and said fourth domain is selected from group consisting of KSN, AEVKKNA (SEQ ID NO:17), NIAKGCKVNCYP (SEQ ID NO:20), DAVN (SEQ ID NO:21), AGRLDLSKFP (SEQ ID NO:30) and ALKA (SEQ ID NO:33), wherein &ggr; is gamma-carboxy glutamate, (iii) the conantokin S1 in which at least one of said Xaa2 residues is substituted with an amino acid selected from the goup consisting of Ser, Ala, Glu and Tyr, (iv) the conantokin peptide chimera of (ii) in which at least one of said &ggr; residues in the second, third and fourth domains is substituted with an amino acid selected from the group consisting of Ser, Ala, Glu and Tyr, (v) the conantokin S1 of (i) or (iii) which is modified by deleting one to five of the C-terminal amino acid residues, and (vi) the conantokin peptide chimera of (ii) or (iv) which is modified by deleting one to five of the C-terminal amino acid residues, with the provisos that (a) when the third domain is LIR&ggr; (SEQ ID NO:14) or LAR&ggr; (SEQ ID NO:19) and the fourth domain is KSN, then the second domain is YQKML&ggr; (SEQ ID NO:15), VAKMAA&ggr; (SEQ ID NO:18), YSKFI&ggr; (SEQ ID NO:28) or YRKAMA&ggr; (SEQ ID NO:31) and (b) when the second domain is YQKML&ggr; (SEQ ID NO:15) and the third domain is NLR&ggr; (SEQ ID NO:16) then the fourth domain is not AEVKKNA (SEQ ID NO:17).