ES2238074T3 - Uso de depuradores, inhibidores o antagonistas de no en el tratamiento de la migraña. - Google Patents
Uso de depuradores, inhibidores o antagonistas de no en el tratamiento de la migraña.Info
- Publication number
- ES2238074T3 ES2238074T3 ES95918128T ES95918128T ES2238074T3 ES 2238074 T3 ES2238074 T3 ES 2238074T3 ES 95918128 T ES95918128 T ES 95918128T ES 95918128 T ES95918128 T ES 95918128T ES 2238074 T3 ES2238074 T3 ES 2238074T3
- Authority
- ES
- Spain
- Prior art keywords
- headache
- migraine
- inhibitor
- antagonist
- vascular
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 239000003112 inhibitor Substances 0.000 title claims abstract description 33
- 239000005557 antagonist Substances 0.000 title claims abstract description 15
- 208000019695 Migraine disease Diseases 0.000 claims abstract description 48
- 206010027599 migraine Diseases 0.000 claims abstract description 44
- 208000001407 Vascular Headaches Diseases 0.000 claims abstract description 12
- 241000124008 Mammalia Species 0.000 claims abstract description 7
- 230000000069 prophylactic effect Effects 0.000 claims abstract description 5
- 230000001154 acute effect Effects 0.000 claims abstract description 4
- 206010019233 Headaches Diseases 0.000 claims description 63
- 231100000869 headache Toxicity 0.000 claims description 60
- 102000008299 Nitric Oxide Synthase Human genes 0.000 claims description 27
- 108010021487 Nitric Oxide Synthase Proteins 0.000 claims description 27
- 150000003839 salts Chemical class 0.000 claims description 16
- 239000004480 active ingredient Substances 0.000 claims description 10
- NTNWOCRCBQPEKQ-YFKPBYRVSA-N N(omega)-methyl-L-arginine Chemical compound CN=C(N)NCCC[C@H](N)C(O)=O NTNWOCRCBQPEKQ-YFKPBYRVSA-N 0.000 claims description 8
- NTNWOCRCBQPEKQ-UHFFFAOYSA-N NG-mono-methyl-L-arginine Natural products CN=C(N)NCCCC(N)C(O)=O NTNWOCRCBQPEKQ-UHFFFAOYSA-N 0.000 claims description 8
- 230000002792 vascular Effects 0.000 claims description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 239000013543 active substance Substances 0.000 claims description 3
- -1 amino, methylamino, ethylamino, hydrazino, methyl Chemical group 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 125000000614 1,2-naphthoquinonyl group Chemical class C1(C(C(=CC2=CC=CC=C12)*)=O)=O 0.000 claims description 2
- 102000004654 Cyclic GMP-Dependent Protein Kinases Human genes 0.000 claims description 2
- 108010003591 Cyclic GMP-Dependent Protein Kinases Proteins 0.000 claims description 2
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 claims description 2
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 claims description 2
- 150000001408 amides Chemical class 0.000 claims description 2
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 claims 1
- 229940094419 Guanylate cyclase inhibitor Drugs 0.000 claims 1
- 239000003126 guanylate cyclase inhibitor Substances 0.000 claims 1
- 239000002516 radical scavenger Substances 0.000 abstract 1
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 98
- SNIOPGDIGTZGOP-UHFFFAOYSA-N Nitroglycerin Chemical compound [O-][N+](=O)OCC(O[N+]([O-])=O)CO[N+]([O-])=O SNIOPGDIGTZGOP-UHFFFAOYSA-N 0.000 description 36
- 229960003711 glyceryl trinitrate Drugs 0.000 description 36
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 26
- 230000000694 effects Effects 0.000 description 23
- 230000015572 biosynthetic process Effects 0.000 description 18
- 238000001802 infusion Methods 0.000 description 18
- 238000009472 formulation Methods 0.000 description 17
- 239000000203 mixture Substances 0.000 description 17
- 230000010339 dilation Effects 0.000 description 14
- 229960001340 histamine Drugs 0.000 description 13
- 208000002193 Pain Diseases 0.000 description 11
- 208000006561 Cluster Headache Diseases 0.000 description 8
- 239000000006 Nitroglycerin Substances 0.000 description 8
- 230000002490 cerebral effect Effects 0.000 description 8
- 208000018912 cluster headache syndrome Diseases 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- 239000003826 tablet Substances 0.000 description 7
- 239000008280 blood Substances 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 6
- 210000004204 blood vessel Anatomy 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 6
- 238000001990 intravenous administration Methods 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 210000003657 middle cerebral artery Anatomy 0.000 description 6
- 210000005036 nerve Anatomy 0.000 description 6
- 230000004044 response Effects 0.000 description 6
- 102100038518 Calcitonin Human genes 0.000 description 5
- 108090000932 Calcitonin Gene-Related Peptide Proteins 0.000 description 5
- 241000282412 Homo Species 0.000 description 5
- 239000004615 ingredient Substances 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 108010078321 Guanylate Cyclase Proteins 0.000 description 4
- 102000014469 Guanylate cyclase Human genes 0.000 description 4
- 210000001367 artery Anatomy 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 229940088598 enzyme Drugs 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 208000008548 Tension-Type Headache Diseases 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 210000004556 brain Anatomy 0.000 description 3
- 210000001627 cerebral artery Anatomy 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 210000003038 endothelium Anatomy 0.000 description 3
- KAQKFAOMNZTLHT-VVUHWYTRSA-N epoprostenol Chemical compound O1C(=CCCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)CCCCC)[C@H](O)C[C@@H]21 KAQKFAOMNZTLHT-VVUHWYTRSA-N 0.000 description 3
- 229960001123 epoprostenol Drugs 0.000 description 3
- 125000003976 glyceryl group Chemical group [H]C([*])([H])C(O[H])([H])C(O[H])([H])[H] 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 230000001939 inductive effect Effects 0.000 description 3
- 238000011835 investigation Methods 0.000 description 3
- 230000007310 pathophysiology Effects 0.000 description 3
- 239000000902 placebo Substances 0.000 description 3
- 229940068196 placebo Drugs 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 230000035945 sensitivity Effects 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 241000894007 species Species 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- QDZOEBFLNHCSSF-PFFBOGFISA-N (2S)-2-[[(2R)-2-[[(2S)-1-[(2S)-6-amino-2-[[(2S)-1-[(2R)-2-amino-5-carbamimidamidopentanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-N-[(2R)-1-[[(2S)-1-[[(2R)-1-[[(2S)-1-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]pentanediamide Chemical compound C([C@@H](C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](N)CCCNC(N)=N)C1=CC=CC=C1 QDZOEBFLNHCSSF-PFFBOGFISA-N 0.000 description 2
- KRQUFUKTQHISJB-YYADALCUSA-N 2-[(E)-N-[2-(4-chlorophenoxy)propoxy]-C-propylcarbonimidoyl]-3-hydroxy-5-(thian-3-yl)cyclohex-2-en-1-one Chemical compound CCC\C(=N/OCC(C)OC1=CC=C(Cl)C=C1)C1=C(O)CC(CC1=O)C1CCCSC1 KRQUFUKTQHISJB-YYADALCUSA-N 0.000 description 2
- 244000215068 Acacia senegal Species 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 208000003098 Ganglion Cysts Diseases 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 229920000084 Gum arabic Polymers 0.000 description 2
- 206010021143 Hypoxia Diseases 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 208000007920 Neurogenic Inflammation Diseases 0.000 description 2
- 102400000096 Substance P Human genes 0.000 description 2
- 101800003906 Substance P Proteins 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 208000005400 Synovial Cyst Diseases 0.000 description 2
- 235000010489 acacia gum Nutrition 0.000 description 2
- 239000000205 acacia gum Substances 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 230000001174 ascending effect Effects 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000005515 coenzyme Substances 0.000 description 2
- 238000007906 compression Methods 0.000 description 2
- 230000006835 compression Effects 0.000 description 2
- 230000001054 cortical effect Effects 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 239000002158 endotoxin Substances 0.000 description 2
- 239000000835 fiber Substances 0.000 description 2
- 230000007954 hypoxia Effects 0.000 description 2
- 230000002779 inactivation Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 230000028161 membrane depolarization Effects 0.000 description 2
- 206010052787 migraine without aura Diseases 0.000 description 2
- 238000000465 moulding Methods 0.000 description 2
- 210000002464 muscle smooth vascular Anatomy 0.000 description 2
- 210000004126 nerve fiber Anatomy 0.000 description 2
- 210000002569 neuron Anatomy 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 239000000651 prodrug Substances 0.000 description 2
- 229940002612 prodrug Drugs 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 230000001953 sensory effect Effects 0.000 description 2
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
- 239000012453 solvate Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 241000416162 Astragalus gummifer Species 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- 102000055006 Calcitonin Human genes 0.000 description 1
- 108060001064 Calcitonin Proteins 0.000 description 1
- 206010008190 Cerebrovascular accident Diseases 0.000 description 1
- 101710095468 Cyclase Proteins 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- 241001269524 Dura Species 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 102000003834 Histamine H1 Receptors Human genes 0.000 description 1
- 108090000110 Histamine H1 Receptors Proteins 0.000 description 1
- 229940124056 Histamine H1 receptor antagonist Drugs 0.000 description 1
- 102000000543 Histamine Receptors Human genes 0.000 description 1
- 108010002059 Histamine Receptors Proteins 0.000 description 1
- 206010058490 Hyperoxia Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- KLDXJTOLSGUMSJ-JGWLITMVSA-N Isosorbide Chemical compound O[C@@H]1CO[C@@H]2[C@@H](O)CO[C@@H]21 KLDXJTOLSGUMSJ-JGWLITMVSA-N 0.000 description 1
- PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 1
- 229930064664 L-arginine Natural products 0.000 description 1
- 235000014852 L-arginine Nutrition 0.000 description 1
- 201000009906 Meningitis Diseases 0.000 description 1
- QPCDCPDFJACHGM-UHFFFAOYSA-N N,N-bis{2-[bis(carboxymethyl)amino]ethyl}glycine Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(=O)O)CCN(CC(O)=O)CC(O)=O QPCDCPDFJACHGM-UHFFFAOYSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 102000003797 Neuropeptides Human genes 0.000 description 1
- 108090000189 Neuropeptides Proteins 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 206010067482 No adverse event Diseases 0.000 description 1
- 206010033557 Palpitations Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 206010036313 Post-traumatic headache Diseases 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 102000007637 Soluble Guanylyl Cyclase Human genes 0.000 description 1
- 108010007205 Soluble Guanylyl Cyclase Proteins 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric Acid Chemical class [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 206010043269 Tension headache Diseases 0.000 description 1
- 108090000190 Thrombin Proteins 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 229960004308 acetylcysteine Drugs 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 238000002399 angioplasty Methods 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 150000001483 arginine derivatives Chemical class 0.000 description 1
- 210000002565 arteriole Anatomy 0.000 description 1
- 239000000022 bacteriostatic agent Substances 0.000 description 1
- 230000003385 bacteriostatic effect Effects 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 description 1
- 229960004015 calcitonin Drugs 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- CCGSUNCLSOWKJO-UHFFFAOYSA-N cimetidine Chemical compound N#CNC(=N/C)\NCCSCC1=NC=N[C]1C CCGSUNCLSOWKJO-UHFFFAOYSA-N 0.000 description 1
- 229960001380 cimetidine Drugs 0.000 description 1
- 230000004087 circulation Effects 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 206010014599 encephalitis Diseases 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 210000003989 endothelium vascular Anatomy 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- SRMBQCVUAVULDJ-UHFFFAOYSA-N ferrioxamine b Chemical compound [Fe+3].CC(=O)N([O-])CCCCCNC(=O)CCC(=O)N([O-])CCCCCNC(=O)CCC(=O)N([O-])CCCCCN SRMBQCVUAVULDJ-UHFFFAOYSA-N 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- RQFCJASXJCIDSX-UUOKFMHZSA-N guanosine 5'-monophosphate Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H]1O RQFCJASXJCIDSX-UUOKFMHZSA-N 0.000 description 1
- 150000003278 haem Chemical group 0.000 description 1
- 239000000938 histamine H1 antagonist Substances 0.000 description 1
- 239000003485 histamine H2 receptor antagonist Substances 0.000 description 1
- 230000000222 hyperoxic effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- JEIPFZHSYJVQDO-UHFFFAOYSA-N iron(III) oxide Inorganic materials O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 229960002479 isosorbide Drugs 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 230000003859 lipid peroxidation Effects 0.000 description 1
- 150000002632 lipids Chemical group 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 210000002441 meningeal artery Anatomy 0.000 description 1
- YECBIJXISLIIDS-UHFFFAOYSA-N mepyramine Chemical compound C1=CC(OC)=CC=C1CN(CCN(C)C)C1=CC=CC=N1 YECBIJXISLIIDS-UHFFFAOYSA-N 0.000 description 1
- 229960000582 mepyramine Drugs 0.000 description 1
- CXKWCBBOMKCUKX-UHFFFAOYSA-M methylene blue Chemical compound [Cl-].C1=CC(N(C)C)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 CXKWCBBOMKCUKX-UHFFFAOYSA-M 0.000 description 1
- 229960000907 methylthioninium chloride Drugs 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 210000000663 muscle cell Anatomy 0.000 description 1
- 210000000478 neocortex Anatomy 0.000 description 1
- 210000004498 neuroglial cell Anatomy 0.000 description 1
- 150000002823 nitrates Chemical class 0.000 description 1
- 239000002840 nitric oxide donor Substances 0.000 description 1
- 230000003040 nociceptive effect Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 229960003330 pentetic acid Drugs 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000010349 pulsation Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 210000002321 radial artery Anatomy 0.000 description 1
- 150000003254 radicals Chemical group 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000002040 relaxant effect Effects 0.000 description 1
- 230000004648 relaxation of smooth muscle Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 208000018316 severe headache Diseases 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 230000007480 spreading Effects 0.000 description 1
- 238000003892 spreading Methods 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 210000001994 temporal artery Anatomy 0.000 description 1
- 210000000966 temporal muscle Anatomy 0.000 description 1
- 210000001103 thalamus Anatomy 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 238000012549 training Methods 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 210000000427 trigeminal ganglion Anatomy 0.000 description 1
- 210000003901 trigeminal nerve Anatomy 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 210000001170 unmyelinated nerve fiber Anatomy 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/06—Free radical scavengers or antioxidants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pain & Pain Management (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Rheumatology (AREA)
- Biochemistry (AREA)
- Toxicology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Orthopedics, Nursing, And Contraception (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP94610027 | 1994-05-11 | ||
| EP94610027 | 1994-05-11 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2238074T3 true ES2238074T3 (es) | 2005-08-16 |
Family
ID=8218183
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES95918128T Expired - Lifetime ES2238074T3 (es) | 1994-05-11 | 1995-05-10 | Uso de depuradores, inhibidores o antagonistas de no en el tratamiento de la migraña. |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US6265441B1 (enExample) |
| EP (1) | EP0758890B1 (enExample) |
| JP (2) | JPH10500129A (enExample) |
| AT (1) | ATE291909T1 (enExample) |
| AU (1) | AU704059B2 (enExample) |
| CA (1) | CA2189762C (enExample) |
| DE (1) | DE69534118T2 (enExample) |
| DK (1) | DK0758890T3 (enExample) |
| ES (1) | ES2238074T3 (enExample) |
| PT (1) | PT758890E (enExample) |
| SI (1) | SI0758890T1 (enExample) |
| WO (1) | WO1995031195A1 (enExample) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2270531C (en) * | 1996-11-05 | 2011-08-30 | Head Explorer Aps | A method for treating tension-type headache |
| US6284794B1 (en) | 1996-11-05 | 2001-09-04 | Head Explorer Aps | Method for treating tension-type headache with inhibitors of nitric oxide and nitric oxide synthase |
| AU1824300A (en) * | 1998-11-23 | 2000-06-13 | Linden Biotechnology, Inc. | Combination products of a guanylate cyclase inhibitor and a local anesthetic forpain relief |
| US20060247216A1 (en) * | 2002-10-25 | 2006-11-02 | Haj-Yehia Abdullah I | Steroid compounds comprising superoxide dismutase mimic groups and nitric oxide donor groups, and their use in the preparation of medicaments |
| EP1578413A2 (en) * | 2002-11-29 | 2005-09-28 | Yissum Research Development Company of The Hebrew University of Jerusalem | Ace-inhibitors having antioxidant and no-donor activity |
| US20080274206A1 (en) * | 2004-10-07 | 2008-11-06 | Ngen Pharmaceuticals N.V. | Stabilised Oxygen Releasing Composition |
| WO2007009462A2 (en) * | 2005-07-15 | 2007-01-25 | Region Hovedstaden V/Glostrup Hospital | Treatment of migraine and headaches |
| US20090191283A1 (en) * | 2008-01-24 | 2009-07-30 | Oronsky Bryan Todd | Treatment of headaches, neck pain, joint pain and inflammatory-type pain |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9200114D0 (en) * | 1992-01-04 | 1992-02-26 | Scras | Dual inhibitors of no synthase and cyclooxygenase |
| FR2707494B1 (fr) | 1993-07-02 | 1995-08-25 | Roussel Uclaf | Nouvelle utilisation de dérivés de la béta-naphtoquinone ainsi que de leurs sels. |
| SK16396A3 (en) * | 1993-08-12 | 1996-09-04 | Astra Ab | Amidine derivatives with nitric oxide synthetase activities |
| GB9317686D0 (en) | 1993-08-25 | 1993-10-13 | Johnson Matthey Plc | Pharmaceutical compositions |
| EP0759027B1 (en) * | 1994-05-07 | 1999-08-04 | Astra Aktiebolag | Bicyclic amidine derivatives as inhibitors of nitric oxide synthetase |
-
1995
- 1995-05-10 DK DK95918128T patent/DK0758890T3/da active
- 1995-05-10 AU AU24179/95A patent/AU704059B2/en not_active Ceased
- 1995-05-10 WO PCT/IB1995/000415 patent/WO1995031195A1/en not_active Ceased
- 1995-05-10 CA CA002189762A patent/CA2189762C/en not_active Expired - Fee Related
- 1995-05-10 PT PT95918128T patent/PT758890E/pt unknown
- 1995-05-10 ES ES95918128T patent/ES2238074T3/es not_active Expired - Lifetime
- 1995-05-10 SI SI9530716T patent/SI0758890T1/xx unknown
- 1995-05-10 DE DE69534118T patent/DE69534118T2/de not_active Expired - Fee Related
- 1995-05-10 AT AT95918128T patent/ATE291909T1/de not_active IP Right Cessation
- 1995-05-10 US US08/737,311 patent/US6265441B1/en not_active Expired - Fee Related
- 1995-05-10 EP EP95918128A patent/EP0758890B1/en not_active Expired - Lifetime
- 1995-05-10 JP JP7529495A patent/JPH10500129A/ja active Pending
-
2007
- 2007-03-07 JP JP2007057587A patent/JP2007137906A/ja not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| EP0758890A1 (en) | 1997-02-26 |
| DK0758890T3 (da) | 2005-04-18 |
| US6265441B1 (en) | 2001-07-24 |
| AU704059B2 (en) | 1999-04-15 |
| SI0758890T1 (enExample) | 2005-08-31 |
| JPH10500129A (ja) | 1998-01-06 |
| CA2189762A1 (en) | 1995-11-23 |
| CA2189762C (en) | 2009-01-13 |
| JP2007137906A (ja) | 2007-06-07 |
| AU2417995A (en) | 1995-12-05 |
| DE69534118T2 (de) | 2006-02-09 |
| EP0758890B1 (en) | 2005-03-30 |
| DE69534118D1 (de) | 2005-05-04 |
| PT758890E (pt) | 2005-06-30 |
| ATE291909T1 (de) | 2005-04-15 |
| WO1995031195A1 (en) | 1995-11-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US7141606B2 (en) | Gabapentin analogues for sleep disorders | |
| ES2329809T3 (es) | Uso de composiciones muy concentradas de acidos grasos n-3 seleccionados para el tratamiento de transtornos del sistema nervioso central. | |
| US20040067986A1 (en) | Neuro-degenerative inhibitor, neuro-endocrine modulator, and neuro-cerebral metabolism enhancer | |
| ES2238074T3 (es) | Uso de depuradores, inhibidores o antagonistas de no en el tratamiento de la migraña. | |
| AU2008248382A1 (en) | Droxidopa and pharmaceutical composition thereof for the treatment of mood disorders, sleep disorders, or attention deficit disorders | |
| JP2023030158A (ja) | 外傷性脳傷害を治療するための組成物および方法 | |
| ES2262801T3 (es) | Uso de un compuesto de carbamato para la prevencion o el tratamiento de trastorno bipolar. | |
| ES2194618T3 (es) | Nueva formulacion de mirtazapina. | |
| MXPA05006209A (es) | Pregabalina y sus derivados para el tratamiento de fibromialgia y otros trastornos relacionados. | |
| ES2528033T3 (es) | Efectos terapéuticos de las briostatinas sobre la alteración de la memoria inducida por isquemia/accidente vascular cerebral y lesiones cerebrales | |
| Onose et al. | Traumatic brain injury: Current endeavours and trends for neuroprotection and related recovery | |
| RU2096034C1 (ru) | Фармацевтическая композиция, индуцирующая биосинтез глутатиона, активность глутатионтрансферазы и оказывающая антитоксическое, радиопротекторное и антигипоксическое действие, и способы лечения, профилактики и защиты с ее использованием | |
| US20160243070A1 (en) | Oxybutynin transdermal therapeutic system combination | |
| KR100841035B1 (ko) | 감마-부티로베타인을 포함하여 이루어지는 약제학적 조성물 | |
| EP0413694B1 (fr) | Preparations medicamenteuses cardio-protectrices comprenant l'amiodarone, un derive nitre, notamment le dinitrate d'isosorbide et facultativement un beta-bloqueur | |
| ES2375347T3 (es) | Métodos y composiciones para el tratamiento del alcoholismo y la dependencia del alcohol. | |
| ES2326355B1 (es) | Acido 1-(di-n-propilacetilaminometil)-ciclohexilacetico. | |
| Cotzias et al. | Some newer metabolic concepts in the treatment of parkinsonism | |
| US11826326B2 (en) | Benzoic acid or a salt and derivative thereof for use in preventing or treating depression | |
| CA2513129A1 (en) | Attaining sexual wellness and health of the sexual vascular system with proanthocyanidins | |
| US20220062217A1 (en) | Prophylaxis and mitigation of migraine headaches using dietary precursors, phospholipids, minerals and other ketogenic sources | |
| FR2647345A1 (fr) | Association de l-5-hydroxy-tryptophane et de benserazide a titre de composition pharmaceutique, notamment utile dans le traitement des troubles de l'equilibre et l'ataxie, cerebelleux ou autres, de toutes origines, et son utilisation pour la preparation de ladite composition | |
| Tegeler | Cholinergic Drugs for the Treatment of Tardive Dyskinesia | |
| HK40016595A (en) | Lipoyl-glu-ala for the treatment of neurodegenerative damage caused by traumatic brain injury | |
| HK40016595B (en) | Lipoyl-glu-ala for the treatment of neurodegenerative damage caused by traumatic brain injury |