1. A method of screening for a compound or a salt thereof that inhibits the activity of a protein comprising the same or substantially the same amino acid sequence as represented by SEQ ID NO: 1, a partial peptide thereof, or a salt thereof, which comprises using a protein comprising the same or substantially the same amino acid sequence as represented by SEQ ID NO: 1, a partial peptide thereof, or a salt thereof.
2. A kit for screening a compound or a salt thereof that inhibits the activity of a protein comprising the same or substantially the same amino acid sequence as represented by SEQ ID NO: 1, a partial peptide thereof, or a salt thereof, which contains a protein comprising the same or substantially the same amino acid sequence as represented by SEQ ID NO: 1, a partial peptide thereof, or a salt thereof.
3. A compound or a salt thereof that inhibits the activity of a protein comprising the same or substantially the same amino acid sequence as represented by SEQ ID NO: 1, a partial peptide thereof, or a salt thereof, wherein said compound or salt thereof is obtainable by using the screening method according to claim 1 or the screening kit according to claim 2.
4. A medicine comprising the compound or salt thereof according to claim 3.
5. The medicine according to claim 4, which is a prophylactic andor therapeutic agent for respiratory diseases.
6. The medicine according to claim 5, wherein the respiratory disease is a chronic obstructive pulmonary disease or bronchial asthma.
7. A method of screening for a compound or a salt thereof that inhibits the expression of the gene for a protein comprising the same or substantially the same amino acid sequence as represented by SEQ ID NO: 1, which comprises using a polynucleotide comprising a polynucleotide encoding said protein or a partial peptide thereof.
8. A screening kit for a compound or a salt thereof that inhibits the expression of the gene for a protein comprising the same or substantially the same amino acid sequence as represented by SEQ ID NO: 1, which contains a polynucleotide comprising a polynucleotide encoding said protein or a partial peptide thereof.
9. A compound or a salt thereof that inhibits the expression of the gene for a protein comprising the same or substantially the same amino acid sequence as represented by SEQ ID NO: 1, wherein said compound or salt thereof is obtainable by using the screening method according to claim 7 or the screening kit according to claim 8.
10. A medicine comprising the compound or salt thereof according to claim 9.
11. The medicine according to claim 10, which is a prophylactic andor therapeutic agent for respiratory diseases.
12. The medicine according to claim 11, wherein the respiratory disease is a chronic obstructive pulmonary disease or bronchial asthma.
13. An antisense polynucleotide comprising a nucleotide sequence, or a part thereof, that is complementary or substantially complementary to the nucleotide sequence of a DNA encoding a protein comprising the same or substantially the same amino acid sequence as represented by SEQ ID NO: 1 or a partial peptide of said protein.
14. A medicine comprising the antisense polynucleotide according to claim 13.
15. The medicine according to claim 14, which is a prophylactic andor therapeutic agent for respiratory diseases.
16. The medicine according to claim 15, wherein the respiratory disease is a chronic obstructive pulmonary disease or bronchial asthma.
17. An antibody to a protein comprising the same or substantially the same amino acid sequence as represented by SEQ ID NO: 1, a partial peptide thereof, or a salt thereof.
18. A method of quantitatively determining a protein comprising the same or substantially the same amino acid sequence as represented by SEQ ID NO: 1, a partial peptide thereof, or a salt thereof, which comprises using the antibody according to claim 17.
19. A medicine comprising the antibody according to claim 17.
20. A diagnostic agent comprising the antibody according to claim 14.
21. The medicine according to claim 19, which is a prophylactic andor therapeutic agent for respiratory diseases.
22. The medicine according to claim 21, wherein the respiratory disease is a chronic obstructive pulmonary disease or bronchial asthma.
23. The diagnostic agent according to claim 20, which is a diagnostic agent for respiratory diseases.
24. The diagnostic agent according to claim 23, wherein the respiratory disease is a chronic obstructive pulmonary disease or bronchial asthma.
25. A method of diagnosing respiratory diseases, comprising using the quantitative determination method according to claim 18.
26. A method of screening for a compound or a salt thereof that inhibits the production of a protein comprising the same or substantially the same amino acid sequence as represented by SEQ ID NO: 1, which comprises using the antibody according to claim 17.
27. A kit for screening for a compound or a salt thereof that inhibits the. production of a protein comprising the same or substantially the same amino acid sequence as represented by SEQ ID NO: 1, which contains the antibody according to claim 17.
28. A compound or a salt thereof that inhibits the production of a protein comprising the same or substantially the same amino acid sequence as represented by SEQ ID NO: 1, wherein said compound or salt thereof is obtainable by using the screening method according to claim 26 or the screening kit according to claim 27.
29. A medicine comprising the compound or salt thereof according to claim 28.
30. The medicine according to claim 29, which is a prophylactic andor therapeutic agent for respiratory diseases.
31. The medicine according to claim 30, wherein the respiratory disease is a chronic obstructive pulmonary disease or bronchial asthma.
32. A diagnostic agent comprising a DNA encoding a protein comprising the same or substantially the same amino acid sequence as represented by SEQ ID NO: 1 or a partial peptide thereof.
33. The diagnostic agent according to claim 32, which is a diagnostic agent for respiratory diseases.
34. The diagnostic agent according to claim 33, wherein the respiratory disease is a chronic obstructive pulmonary disease or bronchial asthma.
35. A prophylactic andor therapeutic agent for respiratory diseases, comprising a compound or a salt thereof that inhibits the activity of a protein comprising the same or substantially the same amino acid sequence as represented by SEQ ID NO: 1, a partial peptide thereof, or a salt thereof; a compound or a salt thereof that inhibits the expression of the gene for said protein; or a compound or a salt thereof that inhibits the production of said protein.
36. A method of preventing andor treating a respiratory disease, comprising administering to a mammal an effective amount of the compound or salt thereof according to claim 3, 9 or 28.
37. A method of preventing andor treating a respiratory disease, comprising administering to a mammal an effective amount of the antisense polynucleotide according to claim 13.
38. A method of preventing andor treating a respiratory disease, comprising administering to a mammal an effective amount of the antibody according to claim 17.
39. A method of preventing andor treating a respiratory disease, comprising administering to a mammal an effective amount of a compound or a salt thereof that inhibits the activity of a protein comprising the same or substantially the same amino acid sequence as represented by SEQ ID NO: 1, a partial peptide thereof, or a salt thereof; a compound or a salt thereof that inhibits the expression of the gene for said protein; or a compound or a salt thereof that inhibits the production of said protein.
40. Use of the compound or salt thereof according to claim 3, 9 or 28 for producing a prophylactic andor therapeutic agent for respiratory diseases.
41. Use of the antisense polynucleotide according to claim 13 or a salt thereof for producing a prophylactic andor therapeutic agent for respiratory diseases.
42. Use of the antibody according to claim 17 for producing a prophylactic andor therapeutic agent for respiratory diseases.
43. Use of a compound or a salt thereof that inhibits the activity of a protein comprising the same or substantially the same amino acid sequence as represented by SEQ ID NO: 1, a partial peptide thereof, or a salt thereof; a compound or a salt thereof that inhibits the expression of the gene for said protein; or a compound or a salt thereof that inhibits the production of said protein; for producing a prophylactic andor therapeutic agent for respiratory diseases.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A method of controlling hippocampal neural circuit hyperexcitability occurring in a neurological disease or disorder associated with epileptogenesis in a subject in need of such treatment, comprising the step of:
contacting the hippocampus in said subject with a compound effective to restore excitatoryinhibitor balance thereby controlling the neural circuit hyperexcitability.
2. The method of claim 1, wherein said compound is selected from the group consisting of adenosine, an adenosine mimetic, an adenosine modulator, an adenosine transport inhibitor and an adenosine receptor agonist.
3. The method of claim 2, wherein said adenosine receptor agonist is a adenosine receptor congener, N6-cyclopentyladenosine, N6-cyclohexyladenosine, 2-chloro-cyclopentyladenosine, N-(3(R))-tetrahydrofuranyl)-6-aminopurine riboside, or a nucleoside transporter.
4. The method of claim 2, wherein said adenosine transport inhibitor is dipyridamole, nitrobenzylthioinosine, dilazep, benzodiazepine, dihydropyridies, xanthine or quinoline derivatives.
5. The method of claim 2, wherein said adenosine modulator is selected from the group consisting of an ecto-5\u2032-nucleotidase inhibitor, an adenosine kinase inhibitor, a S-adenosylhomocysteine hydrolase inhibitor, and an adenosine diaminase inhibitor.
6. The method of claim 1, wherein said subject suitable for selection is one with intractable epilepsy, Dravet’s syndrome, febrile seizures, autism spectrum disorder or attention deficit hyperactivity disorder.
7. The method of claim 1, further comprising the step of administering a GABA modulating composition, an anticonvulsant agent, an ion channel inactivator, or a combination thereof.
8. The method of claim 7, wherein the GABA-modulating composition is selected from the group consisting of barbiturates, benzodiazepines, Gabapentin, Pregabalin, 4-aminobutanoic acid (GABA), 4-amino-3-(4-chlorophenyl)butanoic acid (baclofen), 4-amino-3-phenylbutanoic acid, 4-amino-3-hydroxybutanoic acid, 4-amino-3-(4-chlorophenyl)-3-hydroxyphenylbutanoic acid, 4-amino-3-(thien-2-yl)butanoic acid, 4-amino-3-(5-chlorothien-2-yl)butanoic acid, 4-amino-3-(5-bromothien-2-yl)butanoic acid, 4-amino-3-(5-methylthien-2-yl)butanoic acid, 4-amino-3-(2-imidazolyl)butanoic acid, 4-guanidino-3-(4-chlorophenyl)butanoic acid, (3-aminopropyl)phosphonous acid, (4-aminobut-2-yl)phosphonous acid, sodium butyrate, (3-amino-2-methylpropyl)phosphonous acid, (3-aminobutyl)phosphonous acid, (3-amino-2-(4-chlorophenyl)propyl)phosphonous acid, (3-amino-2-(4-chlorophenyl)-2-hydroxypropyl)phosphonous acid, (3-amino-2-(4-fluorophenyl)propyl)phosphonous acid, (3-amino-2-phenylpropyl)phosphonous acid, (3-amino-2-hydroxypropyl)phosphonous acid, (E)-(3-aminopropen-1-yl)phosphonous acid, (3-amino-2-cyclohexylpropyl)phosphonous acid, (3-amino-2-benzylpropyl)phosphonous acid, 3-amino-2-(4-methylphenyl)propylphosphonous acid, 3-amino-2-(4-trifluoromethylphenyl)propylphosphonous acid, 3-amino-2-(4-methoxyphenyl)propylphosphonous acid, 3-amino-2-(4-chlorophenyl)-2-hydroxypropylphosphonous acid, (3-aminopropyl)methylphosphinic acid, (3-amino-2-hydroxypropyl)methylphosphinic acid, (3-aminopropyl)(difluoromethyl)phosphinic acid, (4-aminobut-2-yl)methylphosphinic acid, (3-amino-1-hydroxypropyl)methylphosphinic acid, (3-amino-2-hydroxypropyl)(difluoromethyl)phosphinic acid, (E)-(3-aminopropen-1-yl)methylphosphinic acid, (3-amino-2-oxo-propyl)methylphosphinic acid, (3-aminopropyl)hydroxymethylphosphinic acid, (5-aminopent-3-yemethylphosphinic acid, (4-amino-1,1,1-trifluorobut-2-yl)methylphosphinic acid, (3-amino-2-(4-chlorophenyl)propyl)sulfinic acid, and 3-aminopropylsulfinic acid.
9. A method of treating a neurological disease or disorder associated with epileptogenesis in a subject in need of such treatment, comprising the step of:
administering an amount of an adenosine A1 agonist pharmacologically effective to block epileptogenetic activities without blocking excitatory synaptic transmission.
10. The method of claim 9, wherein said adenosine agonist is selected from the group consisting of adenosine, an adenosine mimetic, an adenosine modulator, an adenosine transport inhibitor and an adenosine receptor agonist.
11. The method of claim 9, wherein said adenosine receptor agonist is a adenosine receptor congener, N6-cyclopentyladenosine, N6-cyclohexyladenosine, 2-chloro-cyclopentyladenosine, N-(3(R))-tetrahydrofuranyl)-6-aminopurine riboside, or a nucleoside transporter.
12. The method of claim 9, wherein said adenosine transport inhibitor is dipyridamole, nitrobenzylthioinosine, dilazep, benzodiazepine, dihydropyridies, xanthine or quinoline derivatives.
13. The method of claim 9, wherein said adenosine modulator is selected from the group consisting of an ecto-5\u2032-nucleotidase inhibitor, an adenosine kinase inhibitor, a S-adenosylhomocysteine hydrolase inhibitor, and an adenosine diaminase inhibitor.
14. The method of claim 9, wherein said neurological disease or disorder associated with epileptogenesis is intractable epilepsy, Dravet’s syndrome, febrile seizures, autism spectrum disorder or attention deficit hyperactivity disorder.
15. The method of claim 9, further comprising the step of administering a GABA modulating composition, an anticonvulsant agent, an ion channel inactivator, or a combination thereof.
16. The method of claim 15, wherein the GABA-modulating composition is selected from the group consisting of barbiturates, benzodiazepines, Gabapentin, Pregabalin, 4-aminobutanoic acid (GABA), 4-amino-3-(4-chlorophenyl)butanoic acid (baclofen), 4-amino-3-phenylbutanoic acid, 4-amino-3-hydroxybutanoic acid, 4-amino-3-(4-chlorophenyl)-3-hydroxyphenylbutanoic acid, 4-amino-3-(thien-2-yl)butanoic acid, 4-amino-3-(5-chlorothien-2-yl)butanoic acid, 4-amino-3-(5-bromothien-2-yl)butanoic acid, 4-amino-3-(5-methylthien-2-yl)butanoic acid, 4-amino-3-(2-imidazolyl)butanoic acid, 4-guanidino-3-(4-chlorophenyl)butanoic acid, (3-aminopropyl)phosphonous acid, (4-aminobut-2-yl)phosphonous acid, sodium butyrate, (3-amino-2-methylpropyl)phosphonous acid, (3-aminobutyl)phosphonous acid, (3-amino-2-(4-chlorophenyl)propyl)phosphonous acid, (3-amino-2-(4-chlorophenyl)-2-hydroxypropyl)phosphonous acid, (3-amino-2-(4-fluorophenyl)propyl)phosphonous acid, (3-amino-2-phenylpropyl)phosphonous acid, (3-amino-2-hydroxypropyl)phosphonous acid, (E)-(3-aminopropen-1-yl)phosphonous acid, (3-amino-2-cyclohexylpropyl)phosphonous acid, (3-amino-2-benzylpropyl)phosphonous acid, 3-amino-2-(4-methylphenyl)propylphosphonous acid, 3-amino-2-(4-trifluoromethylphenyl)propylphosphonous acid, 3-amino-2-(4-methoxyphenyl)propylphosphonous acid, 3-amino-2-(4-chlorophenyl)-2-hydroxypropylphosphonous acid, (3-aminopropyl)methylphosphinic acid, (3-amino-2-hydroxypropyl)methylphosphinic acid, (3-aminopropyl)(difluoromethyl)phosphinic acid, (4-aminobut-2-yl)methylphosphinic acid, (3-amino-1-hydroxypropyl)methylphosphinic acid, (3-amino-2-hydroxypropyl)(difluoromethyl)phosphinic acid, (E)-(3-aminopropen-1-yl)methylphosphinic acid, (3-amino-2-oxo-propyl)methylphosphinic acid, (3-aminopropyl)hydroxymethylphosphinic acid, (5-aminopent-3-yemethylphosphinic acid, (4-amino-1,1,1-trifluorobut-2-yl)methylphosphinic acid, (3-amino-2-(4-chlorophenyl)propyl)sulfinic acid, and 3-aminopropylsulfinic acid.
17. A method of treating severe myoclonic epilepsy in a subject in a subject in need of such treatment, comprising the step of:
administering an amount of an adenosine A1 agonist pharmacologically effective to treat said severe myoclonic epilepsy.
18. The method of claim 17, wherein said adenosine A1 agonist is selected from the group consisting of adenosine, an adenosine mimetic, an adenosine modulator, an adenosine transport inhibitor and an adenosine receptor agonist.
19. The method of claim 17, wherein said adenosine receptor agonist is a adenosine receptor congener, N6-cyclopentyladenosine, N6-cyclohexyladenosine, 2-chloro-cyclopentyladenosine, N-(3(R))-tetrahydrofuranyl)-6-aminopurine riboside, or a nucleoside transporter.
20. The method of claim 17, wherein said adenosine transport inhibitor is dipyridamole, nitrobenzylthioinosine, dilazep, benzodiazepine, dihydropyridies, xanthine or quinoline derivatives.
21. The method of claim 17, wherein said adenosine modulator is selected from the group consisting of an ecto-5\u2032-nucleotidase inhibitor, an adenosine kinase inhibitor, a S-adenosylhomocysteine hydrolase inhibitor, and an adenosine diaminase inhibitor.
22. The method of claim 17, further comprising the step of administering a GABA modulating composition, an anticonvulsant agent, an ion channel inactivator, or a combination thereof.
23. The method of claim 17, wherein the GABA-modulating composition is selected from the group consisting of barbiturates, benzodiazepines, Gabapentin, Pregabalin, 4-aminobutanoic acid (GABA), 4-amino-3-(4-chlorophenyl)butanoic acid (baclofen), 4-amino-3-phenylbutanoic acid, 4-amino-3-hydroxybutanoic acid, 4-amino-3-(4-chlorophenyl)-3-hydroxyphenylbutanoic acid, 4-amino-3-(thien-2-yl)butanoic acid, 4-amino-3-(5-chlorothien-2-yl)butanoic acid, 4-amino-3-(5-bromothien-2-yl)butanoic acid, 4-amino-3-(5-methylthien-2-yl)butanoic acid, 4-amino-3-(2-imidazolyl)butanoic acid, 4-guanidino-3-(4-chlorophenyl)butanoic acid, (3-aminopropyl)phosphonous acid, (4-aminobut-2-yl)phosphonous acid, sodium butyrate, (3-amino-2-methylpropyl)phosphonous acid, (3-aminobutyl)phosphonous acid, (3-amino-2-(4-chlorophenyl)propyl)phosphonous acid, (3-amino-2-(4-chlorophenyl)-2-hydroxypropyl)phosphonous acid, (3-amino-2-(4-fluorophenyl)propyl)phosphonous acid, (3-amino-2-phenylpropyl)phosphonous acid, (3-amino-2-hydroxypropyl)phosphonous acid, (E)-(3-aminopropen-1-yl)phosphonous acid, (3-amino-2-cyclohexylpropyl)phosphonous acid, (3-amino-2-benzylpropyl)phosphonous acid, 3-amino-2-(4-methylphenyl)propylphosphonous acid, 3-amino-2-(4-trifluoromethylphenyl)propylphosphonous acid, 3-amino-2-(4-methoxyphenyl)propylphosphonous acid, 3-amino-2-(4-chlorophenyl)-2-hydroxypropylphosphonous acid, (3-aminopropyl)methylphosphinic acid, (3-amino-2-hydroxypropyl)methylphosphinic acid, (3-aminopropyl)(difluoromethyl)phosphinic acid, (4-aminobut-2-yl)methylphosphinic acid, (3-amino-1-hydroxypropyl)methylphosphinic acid, (3-amino-2-hydroxypropyl)(difluoromethyl)phosphinic acid, (E)-(3-aminopropen-1-yl)methylphosphinic acid, (3-amino-2-oxo-propyl)methylphosphinic acid, (3-aminopropyl)hydroxymethylphosphinic acid, (5-aminopent-3-yemethylphosphinic acid, (4-amino-1,1,1-trifluorobut-2-yl)methylphosphinic acid, (3-amino-2-(4-chlorophenyl)propyl)sulfinic acid, and 3-aminopropylsulfinic acid.