AU731656B2 - Method of treating heart failure - Google Patents
Method of treating heart failure Download PDFInfo
- Publication number
- AU731656B2 AU731656B2 AU81740/98A AU8174098A AU731656B2 AU 731656 B2 AU731656 B2 AU 731656B2 AU 81740/98 A AU81740/98 A AU 81740/98A AU 8174098 A AU8174098 A AU 8174098A AU 731656 B2 AU731656 B2 AU 731656B2
- Authority
- AU
- Australia
- Prior art keywords
- dose
- adrenergic receptor
- heart failure
- metoprolol
- positive inotropic
- 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.)
- Ceased
Links
- 206010019280 Heart failures Diseases 0.000 title claims description 58
- 238000000034 method Methods 0.000 title claims description 37
- 239000000674 adrenergic antagonist Substances 0.000 claims description 53
- 239000004041 inotropic agent Substances 0.000 claims description 50
- IUBSYMUCCVWXPE-UHFFFAOYSA-N metoprolol Chemical compound COCCC1=CC=C(OCC(O)CNC(C)C)C=C1 IUBSYMUCCVWXPE-UHFFFAOYSA-N 0.000 claims description 30
- 229960002237 metoprolol Drugs 0.000 claims description 30
- 229960000972 enoximone Drugs 0.000 claims description 28
- ZJKNESGOIKRXQY-UHFFFAOYSA-N enoximone Chemical group C1=CC(SC)=CC=C1C(=O)C1=C(C)NC(=O)N1 ZJKNESGOIKRXQY-UHFFFAOYSA-N 0.000 claims description 28
- 206010007558 Cardiac failure chronic Diseases 0.000 claims description 5
- 230000000004 hemodynamic effect Effects 0.000 claims description 5
- 230000000694 effects Effects 0.000 description 69
- 108060003345 Adrenergic Receptor Proteins 0.000 description 28
- 102000017910 Adrenergic receptor Human genes 0.000 description 28
- 102000005962 receptors Human genes 0.000 description 26
- 108020003175 receptors Proteins 0.000 description 26
- 238000011282 treatment Methods 0.000 description 24
- IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 23
- 230000000297 inotrophic effect Effects 0.000 description 21
- 239000000556 agonist Substances 0.000 description 18
- 102000030621 adenylate cyclase Human genes 0.000 description 17
- 108060000200 adenylate cyclase Proteins 0.000 description 17
- 229940079593 drug Drugs 0.000 description 16
- 239000003814 drug Substances 0.000 description 16
- 238000002560 therapeutic procedure Methods 0.000 description 16
- ZVNYJIZDIRKMBF-UHFFFAOYSA-N Vesnarinone Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)N1CCN(C=2C=C3CCC(=O)NC3=CC=2)CC1 ZVNYJIZDIRKMBF-UHFFFAOYSA-N 0.000 description 15
- 230000004083 survival effect Effects 0.000 description 15
- 229950005577 vesnarinone Drugs 0.000 description 15
- 230000002411 adverse Effects 0.000 description 13
- 230000009249 intrinsic sympathomimetic activity Effects 0.000 description 12
- 230000001800 adrenalinergic effect Effects 0.000 description 11
- 239000011575 calcium Substances 0.000 description 11
- 239000005557 antagonist Substances 0.000 description 10
- 230000000747 cardiac effect Effects 0.000 description 10
- 229940125425 inverse agonist Drugs 0.000 description 10
- 230000037361 pathway Effects 0.000 description 10
- 230000004044 response Effects 0.000 description 10
- 230000006870 function Effects 0.000 description 9
- 229960003574 milrinone Drugs 0.000 description 9
- PZRHRDRVRGEVNW-UHFFFAOYSA-N milrinone Chemical compound N1C(=O)C(C#N)=CC(C=2C=CN=CC=2)=C1C PZRHRDRVRGEVNW-UHFFFAOYSA-N 0.000 description 9
- 102000008130 Cyclic AMP-Dependent Protein Kinases Human genes 0.000 description 8
- 108010049894 Cyclic AMP-Dependent Protein Kinases Proteins 0.000 description 8
- IVOMOUWHDPKRLL-UHFFFAOYSA-N UNPD107823 Natural products O1C2COP(O)(=O)OC2C(O)C1N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-UHFFFAOYSA-N 0.000 description 8
- 239000003795 chemical substances by application Substances 0.000 description 8
- 229940095074 cyclic amp Drugs 0.000 description 8
- 238000001990 intravenous administration Methods 0.000 description 8
- 239000002571 phosphodiesterase inhibitor Substances 0.000 description 8
- 230000011664 signaling Effects 0.000 description 8
- 230000007246 mechanism Effects 0.000 description 7
- 239000000902 placebo Substances 0.000 description 7
- 229940068196 placebo Drugs 0.000 description 7
- 230000000638 stimulation Effects 0.000 description 7
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 6
- 230000004217 heart function Effects 0.000 description 6
- 230000001976 improved effect Effects 0.000 description 6
- 210000005240 left ventricle Anatomy 0.000 description 6
- 230000026731 phosphorylation Effects 0.000 description 6
- 238000006366 phosphorylation reaction Methods 0.000 description 6
- 238000002054 transplantation Methods 0.000 description 6
- 230000024883 vasodilation Effects 0.000 description 6
- 230000002861 ventricular Effects 0.000 description 6
- 239000005541 ACE inhibitor Substances 0.000 description 5
- 108091006146 Channels Proteins 0.000 description 5
- 108010061435 Enalapril Proteins 0.000 description 5
- 241000282320 Panthera leo Species 0.000 description 5
- 239000000048 adrenergic agonist Substances 0.000 description 5
- 229940126157 adrenergic receptor agonist Drugs 0.000 description 5
- 230000027455 binding Effects 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- 208000029078 coronary artery disease Diseases 0.000 description 5
- 230000003247 decreasing effect Effects 0.000 description 5
- GBXSMTUPTTWBMN-XIRDDKMYSA-N enalapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(O)=O)CC1=CC=CC=C1 GBXSMTUPTTWBMN-XIRDDKMYSA-N 0.000 description 5
- 229960000873 enalapril Drugs 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- 230000001105 regulatory effect Effects 0.000 description 5
- 229940099471 Phosphodiesterase inhibitor Drugs 0.000 description 4
- DXPOSRCHIDYWHW-UHFFFAOYSA-N Xamoterol Chemical compound C=1C=C(O)C=CC=1OCC(O)CNCCNC(=O)N1CCOCC1 DXPOSRCHIDYWHW-UHFFFAOYSA-N 0.000 description 4
- 230000004913 activation Effects 0.000 description 4
- 229940082638 cardiac stimulant phosphodiesterase inhibitors Drugs 0.000 description 4
- 230000002526 effect on cardiovascular system Effects 0.000 description 4
- 230000002107 myocardial effect Effects 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 230000019491 signal transduction Effects 0.000 description 4
- 230000007781 signaling event Effects 0.000 description 4
- 229960004928 xamoterol Drugs 0.000 description 4
- FBMYKMYQHCBIGU-UHFFFAOYSA-N 2-[2-hydroxy-3-[[1-(1h-indol-3-yl)-2-methylpropan-2-yl]amino]propoxy]benzonitrile Chemical compound C=1NC2=CC=CC=C2C=1CC(C)(C)NCC(O)COC1=CC=CC=C1C#N FBMYKMYQHCBIGU-UHFFFAOYSA-N 0.000 description 3
- LTMHDMANZUZIPE-AMTYYWEZSA-N Digoxin Natural products O([C@H]1[C@H](C)O[C@H](O[C@@H]2C[C@@H]3[C@@](C)([C@@H]4[C@H]([C@]5(O)[C@](C)([C@H](O)C4)[C@H](C4=CC(=O)OC4)CC5)CC3)CC2)C[C@@H]1O)[C@H]1O[C@H](C)[C@@H](O[C@H]2O[C@@H](C)[C@H](O)[C@@H](O)C2)[C@@H](O)C1 LTMHDMANZUZIPE-AMTYYWEZSA-N 0.000 description 3
- 208000000059 Dyspnea Diseases 0.000 description 3
- 206010013975 Dyspnoeas Diseases 0.000 description 3
- 102000034286 G proteins Human genes 0.000 description 3
- 108091006027 G proteins Proteins 0.000 description 3
- XKMLYUALXHKNFT-UUOKFMHZSA-N Guanosine-5'-triphosphate Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O XKMLYUALXHKNFT-UUOKFMHZSA-N 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 229950005341 bucindolol Drugs 0.000 description 3
- 210000004413 cardiac myocyte Anatomy 0.000 description 3
- NPAKNKYSJIDKMW-UHFFFAOYSA-N carvedilol Chemical compound COC1=CC=CC=C1OCCNCC(O)COC1=CC=CC2=NC3=CC=C[CH]C3=C12 NPAKNKYSJIDKMW-UHFFFAOYSA-N 0.000 description 3
- 229960004195 carvedilol Drugs 0.000 description 3
- 230000001684 chronic effect Effects 0.000 description 3
- 230000009137 competitive binding Effects 0.000 description 3
- 229960005156 digoxin Drugs 0.000 description 3
- LTMHDMANZUZIPE-PUGKRICDSA-N digoxin Chemical compound C1[C@H](O)[C@H](O)[C@@H](C)O[C@H]1O[C@@H]1[C@@H](C)O[C@@H](O[C@@H]2[C@H](O[C@@H](O[C@@H]3C[C@@H]4[C@]([C@@H]5[C@H]([C@]6(CC[C@@H]([C@@]6(C)[C@H](O)C5)C=5COC(=O)C=5)O)CC4)(C)CC3)C[C@@H]2O)C)C[C@@H]1O LTMHDMANZUZIPE-PUGKRICDSA-N 0.000 description 3
- LTMHDMANZUZIPE-UHFFFAOYSA-N digoxine Natural products C1C(O)C(O)C(C)OC1OC1C(C)OC(OC2C(OC(OC3CC4C(C5C(C6(CCC(C6(C)C(O)C5)C=5COC(=O)C=5)O)CC4)(C)CC3)CC2O)C)CC1O LTMHDMANZUZIPE-UHFFFAOYSA-N 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 208000019622 heart disease Diseases 0.000 description 3
- 230000003834 intracellular effect Effects 0.000 description 3
- 210000004165 myocardium Anatomy 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- 230000009090 positive inotropic effect Effects 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 238000011301 standard therapy Methods 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 2
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 2
- 229930182837 (R)-adrenaline Natural products 0.000 description 2
- UUUHXMGGBIUAPW-UHFFFAOYSA-N 1-[1-[2-[[5-amino-2-[[1-[5-(diaminomethylideneamino)-2-[[1-[3-(1h-indol-3-yl)-2-[(5-oxopyrrolidine-2-carbonyl)amino]propanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbon Chemical compound C1CCC(C(=O)N2C(CCC2)C(O)=O)N1C(=O)C(C(C)CC)NC(=O)C(CCC(N)=O)NC(=O)C1CCCN1C(=O)C(CCCN=C(N)N)NC(=O)C1CCCN1C(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C1CCC(=O)N1 UUUHXMGGBIUAPW-UHFFFAOYSA-N 0.000 description 2
- ZKHQWZAMYRWXGA-KQYNXXCUSA-J ATP(4-) Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-J 0.000 description 2
- ZKHQWZAMYRWXGA-UHFFFAOYSA-N Adenosine triphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O ZKHQWZAMYRWXGA-UHFFFAOYSA-N 0.000 description 2
- 206010007559 Cardiac failure congestive Diseases 0.000 description 2
- 208000032862 Clinical Deterioration Diseases 0.000 description 2
- JRWZLRBJNMZMFE-UHFFFAOYSA-N Dobutamine Chemical compound C=1C=C(O)C(O)=CC=1CCNC(C)CCC1=CC=C(O)C=C1 JRWZLRBJNMZMFE-UHFFFAOYSA-N 0.000 description 2
- QGWNDRXFNXRZMB-UUOKFMHZSA-N GDP Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1O[C@H](COP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O QGWNDRXFNXRZMB-UUOKFMHZSA-N 0.000 description 2
- 108091000058 GTP-Binding Proteins 0.000 description 2
- 206010020880 Hypertrophy Diseases 0.000 description 2
- 206010069140 Myocardial depression Diseases 0.000 description 2
- 102000004270 Peptidyl-Dipeptidase A Human genes 0.000 description 2
- 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 2
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 2
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- MMWCIQZXVOZEGG-HOZKJCLWSA-N [(1S,2R,3S,4S,5R,6S)-2,3,5-trihydroxy-4,6-diphosphonooxycyclohexyl] dihydrogen phosphate Chemical compound O[C@H]1[C@@H](O)[C@H](OP(O)(O)=O)[C@@H](OP(O)(O)=O)[C@H](O)[C@H]1OP(O)(O)=O MMWCIQZXVOZEGG-HOZKJCLWSA-N 0.000 description 2
- 230000005856 abnormality Effects 0.000 description 2
- 230000006978 adaptation Effects 0.000 description 2
- UDMBCSSLTHHNCD-KQYNXXCUSA-N adenosine 5'-monophosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H]1O UDMBCSSLTHHNCD-KQYNXXCUSA-N 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 239000002981 blocking agent Substances 0.000 description 2
- 208000006218 bradycardia Diseases 0.000 description 2
- 230000036471 bradycardia Effects 0.000 description 2
- 229940097217 cardiac glycoside Drugs 0.000 description 2
- 239000002368 cardiac glycoside Substances 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 230000002057 chronotropic effect Effects 0.000 description 2
- 230000008828 contractile function Effects 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 230000010339 dilation Effects 0.000 description 2
- 239000002934 diuretic Substances 0.000 description 2
- 229940030606 diuretics Drugs 0.000 description 2
- 229960001089 dobutamine Drugs 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 229960005139 epinephrine Drugs 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 230000029142 excretion Effects 0.000 description 2
- 206010016256 fatigue Diseases 0.000 description 2
- UYGONJYYUKVHDD-UHFFFAOYSA-N flosequinan Chemical compound C1=C(F)C=C2N(C)C=C(S(C)=O)C(=O)C2=C1 UYGONJYYUKVHDD-UHFFFAOYSA-N 0.000 description 2
- 229960001606 flosequinan Drugs 0.000 description 2
- QGWNDRXFNXRZMB-UHFFFAOYSA-N guanidine diphosphate Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(COP(O)(=O)OP(O)(O)=O)C(O)C1O QGWNDRXFNXRZMB-UHFFFAOYSA-N 0.000 description 2
- 230000004941 influx Effects 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 230000033001 locomotion Effects 0.000 description 2
- 230000010534 mechanism of action Effects 0.000 description 2
- 238000013160 medical therapy Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000010016 myocardial function Effects 0.000 description 2
- 229960002748 norepinephrine Drugs 0.000 description 2
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 230000037081 physical activity Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000005086 pumping Methods 0.000 description 2
- 239000002464 receptor antagonist Substances 0.000 description 2
- 229940044551 receptor antagonist Drugs 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 230000000087 stabilizing effect Effects 0.000 description 2
- 229930002534 steroid glycoside Natural products 0.000 description 2
- 150000008143 steroidal glycosides Chemical class 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 230000003442 weekly effect Effects 0.000 description 2
- JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 description 1
- ONELTIQETCJUSG-UHFFFAOYSA-N 2-hydroxypropane-1,2,3-tricarboxylic acid;6-[4-(4-oxo-4-phenylbutyl)piperazine-1-carbonyl]-3,4-dihydro-1h-quinolin-2-one Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.C1CN(C(=O)C=2C=C3CCC(=O)NC3=CC=2)CCN1CCCC(=O)C1=CC=CC=C1 ONELTIQETCJUSG-UHFFFAOYSA-N 0.000 description 1
- KQQFGABYYXEKDM-UHFFFAOYSA-N 4-[3-(1-benzhydrylazetidin-3-yl)oxy-2-hydroxypropoxy]-1h-indole-2-carbonitrile Chemical compound C=1C=CC=2NC(C#N)=CC=2C=1OCC(O)COC(C1)CN1C(C=1C=CC=CC=1)C1=CC=CC=C1 KQQFGABYYXEKDM-UHFFFAOYSA-N 0.000 description 1
- 206010000125 Abnormal dreams Diseases 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- ROFVEXUMMXZLPA-UHFFFAOYSA-N Bipyridyl Chemical compound N1=CC=CC=C1C1=CC=CC=N1 ROFVEXUMMXZLPA-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 229940122434 Calcium sensitizer Drugs 0.000 description 1
- 206010049993 Cardiac death Diseases 0.000 description 1
- 208000031229 Cardiomyopathies Diseases 0.000 description 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
- UDMBCSSLTHHNCD-UHFFFAOYSA-N Coenzym Q(11) Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(O)=O)C(O)C1O UDMBCSSLTHHNCD-UHFFFAOYSA-N 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- 206010011703 Cyanosis Diseases 0.000 description 1
- 206010011906 Death Diseases 0.000 description 1
- 208000020401 Depressive disease Diseases 0.000 description 1
- 201000010046 Dilated cardiomyopathy Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000034354 Gi proteins Human genes 0.000 description 1
- 108091006101 Gi proteins Proteins 0.000 description 1
- 102000056950 Gs GTP-Binding Protein alpha Subunits Human genes 0.000 description 1
- 108091006065 Gs proteins Proteins 0.000 description 1
- 208000013016 Hypoglycemia Diseases 0.000 description 1
- 208000001953 Hypotension Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 206010022562 Intermittent claudication Diseases 0.000 description 1
- 206010022998 Irritability Diseases 0.000 description 1
- 102000003505 Myosin Human genes 0.000 description 1
- 108030001204 Myosin ATPases Proteins 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 208000012322 Raynaud phenomenon Diseases 0.000 description 1
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 1
- 108010052164 Sodium Channels Proteins 0.000 description 1
- 102000018674 Sodium Channels Human genes 0.000 description 1
- 229940122616 Sodium channel agonist Drugs 0.000 description 1
- 206010071436 Systolic dysfunction Diseases 0.000 description 1
- BYKYPZBCMBEEGU-UHFFFAOYSA-N Toborinone Chemical compound C1=C(OC)C(OC)=CC=C1CNCC(O)COC1=CC=C(NC(=O)C=C2)C2=C1 BYKYPZBCMBEEGU-UHFFFAOYSA-N 0.000 description 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- LNQVTSROQXJCDD-UHFFFAOYSA-N adenosine monophosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(CO)C(OP(O)(O)=O)C1O LNQVTSROQXJCDD-UHFFFAOYSA-N 0.000 description 1
- 230000001668 ameliorated effect Effects 0.000 description 1
- 210000003423 ankle Anatomy 0.000 description 1
- 229940045799 anthracyclines and related substance Drugs 0.000 description 1
- 230000003126 arrythmogenic effect Effects 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000003491 cAMP production Effects 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 210000000038 chest Anatomy 0.000 description 1
- 230000001010 compromised effect Effects 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 150000001982 diacylglycerols Chemical class 0.000 description 1
- 201000011304 dilated cardiomyopathy 1A Diseases 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 238000002592 echocardiography Methods 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 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 1
- 229960001123 epoprostenol Drugs 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 230000004907 flux Effects 0.000 description 1
- 210000002683 foot Anatomy 0.000 description 1
- 238000002825 functional assay Methods 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- 230000036543 hypotension Effects 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 229940124975 inotropic drug Drugs 0.000 description 1
- 206010022437 insomnia Diseases 0.000 description 1
- 208000021156 intermittent vascular claudication Diseases 0.000 description 1
- 230000006831 intrinsic signaling Effects 0.000 description 1
- WGSPBWSPJOBKNT-UHFFFAOYSA-N iodocyanopindolol Chemical compound CC(C)NCC(O)COC1=CC=CC2=C1C(I)=C(C#N)N2 WGSPBWSPJOBKNT-UHFFFAOYSA-N 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 229940039009 isoproterenol Drugs 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 238000001325 log-rank test Methods 0.000 description 1
- 238000011866 long-term treatment Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 201000003102 mental depression Diseases 0.000 description 1
- 230000000897 modulatory effect Effects 0.000 description 1
- 210000002464 muscle smooth vascular Anatomy 0.000 description 1
- 210000000107 myocyte Anatomy 0.000 description 1
- 230000008035 nerve activity Effects 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 230000002644 neurohormonal effect Effects 0.000 description 1
- 230000003957 neurotransmitter release Effects 0.000 description 1
- 230000000966 norepinephrine reuptake Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 238000007427 paired t-test Methods 0.000 description 1
- 239000004031 partial agonist Substances 0.000 description 1
- 230000004963 pathophysiological condition Effects 0.000 description 1
- 230000008288 physiological mechanism Effects 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000036316 preload Effects 0.000 description 1
- 230000003518 presynaptic effect Effects 0.000 description 1
- 208000037821 progressive disease Diseases 0.000 description 1
- 230000009822 protein phosphorylation Effects 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 230000009325 pulmonary function Effects 0.000 description 1
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical class C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 description 1
- 150000007660 quinolones Chemical class 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 210000003660 reticulum Anatomy 0.000 description 1
- 210000000518 sarcolemma Anatomy 0.000 description 1
- 210000001908 sarcoplasmic reticulum Anatomy 0.000 description 1
- 230000036299 sexual function Effects 0.000 description 1
- 208000013220 shortness of breath Diseases 0.000 description 1
- 238000001629 sign test Methods 0.000 description 1
- 230000020837 signal transduction in absence of ligand Effects 0.000 description 1
- 230000009131 signaling function Effects 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000003378 sodium channel stimulating agent Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 230000002889 sympathetic effect Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- 230000002792 vascular Effects 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
Landscapes
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Epidemiology (AREA)
- Hospice & Palliative Care (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US5067497P | 1997-06-25 | 1997-06-25 | |
| US60/050674 | 1997-06-25 | ||
| PCT/US1998/013442 WO1998058638A1 (en) | 1997-06-25 | 1998-06-24 | Method of treating heart failure |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU8174098A AU8174098A (en) | 1999-01-04 |
| AU731656B2 true AU731656B2 (en) | 2001-04-05 |
Family
ID=21966696
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU81740/98A Ceased AU731656B2 (en) | 1997-06-25 | 1998-06-24 | Method of treating heart failure |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US5998458A (enExample) |
| EP (1) | EP1017376A4 (enExample) |
| JP (1) | JP2002508766A (enExample) |
| AU (1) | AU731656B2 (enExample) |
| CA (1) | CA2295094A1 (enExample) |
| WO (1) | WO1998058638A1 (enExample) |
Families Citing this family (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1996024358A1 (en) * | 1995-02-10 | 1996-08-15 | G.D. Searle & Co. | Use of low dose amount of spironolactone for treatment of cardiovascular disease |
| AR030414A1 (es) * | 2000-04-03 | 2003-08-20 | Astrazeneca Ab | Combinacion farmaceutica que comprende un beta bloqueante y un inhibidor de hmg-coa reductasa , formulacion farmaceutica, equipo transportable de partes , uso de esta combinacion y de esta formulacion para preparar medicamentos |
| SE0002354D0 (sv) * | 2000-06-22 | 2000-06-22 | Astrazeneca Ab | New formulation |
| FI20010233A0 (fi) * | 2001-02-08 | 2001-02-08 | Orion Corp | Menetelmä sydämen vajaatoiminnan hoitoon |
| FI20011464A0 (fi) | 2001-07-04 | 2001-07-04 | Orion Corp | Yhdistelmäterapia sydämen vajaatoiminnan hoitoon |
| US7020521B1 (en) | 2002-11-08 | 2006-03-28 | Pacesetter, Inc. | Methods and apparatus for detecting and/or monitoring heart failure |
| KR20120008093A (ko) | 2003-11-17 | 2012-01-25 | 노파르티스 아게 | 디펩티딜 펩티다제 ⅳ 억제제의 용도 |
| EP1699436A2 (en) * | 2003-12-12 | 2006-09-13 | Myogen, Inc. | Enoximone formulations and their use in the treatment of cardiac hypertrophy and heart failure |
| JP2007530563A (ja) * | 2004-03-22 | 2007-11-01 | ミオゲン インコーポレイティッド | （ｓ）−エノキシモンスルホキシドおよびｐｄｅ−ｉｉｉ媒介疾患の治療におけるその使用 |
| WO2005092333A1 (en) * | 2004-03-22 | 2005-10-06 | Myogen, Inc. | (r)-enoximone sulfoxide and its use in the treatment of pde-iii mediated diseases |
| WO2006007213A1 (en) * | 2004-06-23 | 2006-01-19 | Myogen, Inc. | Enoximone formulations and their use in the treatment of pde-iii mediated diseases |
| WO2006031955A2 (en) * | 2004-09-14 | 2006-03-23 | The Regents Of The University Of Colorado, A Body Corporate | Method for treatment with bucindolol based on genetic targeting |
| CA2610022A1 (en) | 2005-06-06 | 2006-12-14 | Georgetown University | Compositions and methods for lipo modeling |
| WO2007014033A2 (en) * | 2005-07-22 | 2007-02-01 | The Regents Of The University Of Colorado, A Body Corporate | Inhibition of extracellular signal-regulated kinase 1/2 as a treatment for cardiac hypertrophy and heart failure |
| WO2011032088A1 (en) | 2009-09-11 | 2011-03-17 | Arca Biopharma, Inc. | Polymorphisms in the pde3a gene |
| BR112019013702A2 (pt) * | 2017-01-03 | 2020-03-03 | Cardioxyl Pharmaceuticals, Inc. | Método de administração de compostos doadores de nitroxila |
| IL283725B2 (en) | 2017-06-20 | 2024-04-01 | Imbria Pharmaceuticals Inc | Compositions and methods for increasing efficiency of cardiac metabolism |
| WO2020081361A1 (en) | 2018-10-17 | 2020-04-23 | Imbria Pharmaceuticals, Inc. | Methods of treating rheumatic diseases using trimetazidine-based compounds |
| WO2021225950A1 (en) * | 2020-05-04 | 2021-11-11 | Imbria Pharmaceuticals, Inc. | Dosing methods for treatment of cardiovascular conditions |
| US11530184B2 (en) | 2020-06-30 | 2022-12-20 | Imbria Pharmaceuticals, Inc. | Crystal forms of 2-[4-[(2,3,4-trimethoxyphenyl)methyl]piperazin-1-yl]ethyl pyridine-3-carboxylate |
| US11780811B2 (en) | 2020-06-30 | 2023-10-10 | Imbria Pharmaceuticals, Inc. | Methods of synthesizing 2-[4-[(2,3,4-trimethoxyphenyl)methyl]piperazin-1-yl]ethyl pyridine-3-carboxylate |
| US11883396B2 (en) | 2021-05-03 | 2024-01-30 | Imbria Pharmaceuticals, Inc. | Methods of treating kidney conditions using modified forms of trimetazidine |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE354851B (enExample) * | 1970-02-18 | 1973-03-26 | Haessle Ab | |
| US4405635A (en) * | 1979-06-18 | 1983-09-20 | Merrell Dow Pharmaceuticals Inc. | 4-Aroylimidazol-2-ones and their use as pharmaceuticals |
-
1998
- 1998-06-19 US US09/100,497 patent/US5998458A/en not_active Expired - Lifetime
- 1998-06-24 CA CA002295094A patent/CA2295094A1/en not_active Abandoned
- 1998-06-24 AU AU81740/98A patent/AU731656B2/en not_active Ceased
- 1998-06-24 JP JP50505699A patent/JP2002508766A/ja active Pending
- 1998-06-24 EP EP19980931687 patent/EP1017376A4/en not_active Ceased
- 1998-06-24 WO PCT/US1998/013442 patent/WO1998058638A1/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| US5998458A (en) | 1999-12-07 |
| EP1017376A1 (en) | 2000-07-12 |
| EP1017376A4 (en) | 2002-10-25 |
| CA2295094A1 (en) | 1998-12-30 |
| WO1998058638A1 (en) | 1998-12-30 |
| AU8174098A (en) | 1999-01-04 |
| JP2002508766A (ja) | 2002-03-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU731656B2 (en) | Method of treating heart failure | |
| Metra et al. | Beta-blocker therapy influences the hemodynamic response to inotropic agents in patients with heart failure: a randomized comparison of dobutamine and enoximone before and after chronic treatment with metoprolol or carvedilol | |
| JP2022020624A (ja) | 心房拡大又はリモデリングを特徴とする疾患を治療するためのｎｅｐ阻害剤 | |
| Peart et al. | Cardioprotective effects of acute and chronic opioid treatment are mediated via different signaling pathways | |
| Zhao et al. | Reduced coronary NO production in conscious dogs after the development of alloxan-induced diabetes | |
| Zimmerman et al. | Vasopressors and inotropes | |
| JP2022062174A (ja) | 心毒性を低減するための組成物及び方法 | |
| US9468634B2 (en) | Treatment of heart failure | |
| Larsen et al. | Alveolar hypoxia induces left ventricular diastolic dysfunction and reduces phosphorylation of phospholamban in mice | |
| Mbikou et al. | Cardiovascular effects of DWORF (dwarf open reading frame) peptide in normal and ischaemia/reperfused isolated rat hearts | |
| Chioncel et al. | Pathophysiology and clinical use of agents with vasodilator properties in acute heart failure. A scientific statement of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC) | |
| WO2009066085A1 (en) | Treatment of heart failure with normal ejection fraction | |
| Anderson | Management of beta-adrenergic blocker poisoning | |
| Pouleur et al. | Focus on diastolic dysfunction: a new approach to heart failure therapy. | |
| CA2485600C (en) | 5-ht4 receptor antagonists for the treatment of heart failure | |
| Kiriazis et al. | Chronic activation of the low affinity site of β1‐adrenoceptors stimulates haemodynamics but exacerbates pressure‐overload cardiac remodelling | |
| Andersson et al. | Recovery from left ventricular asynergy in ischemic cardiomyopathy following long-term beta blockade treatment | |
| Kikura et al. | New cardiac drugs | |
| EP3124019B1 (en) | Substance selected among midodrine, a pharmaceutical salt and the active metabolite thereof, for use in the treatment of obstructive cardiopathy | |
| Levy | Support of the perioperative failing heart with preexisting ventricular dysfunction: currently available options | |
| Lomivorotov et al. | Perfusion separation challenge | |
| Young et al. | Mg2+ efflux from the isolated perfused rabbit heart is mediated by two states of the β1-adrenergic receptor | |
| TW202313021A (zh) | 作為強心劑之六氫吡啶脲衍生物 | |
| WO2022232650A1 (en) | Methods for reducing agt expression | |
| EA047888B1 (ru) | Применение производных пиперидин мочевины в качестве инотропных агентов |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FGA | Letters patent sealed or granted (standard patent) | ||
| PC | Assignment registered |
Owner name: UNIVERSITY TECHNOLOGY CORPORATION Free format text: FORMER OWNER WAS: MICHAEL R. BRISTOW |
|
| PC | Assignment registered |
Owner name: THE REGENTS OF THE UNIVERSITY OF COLORADO Free format text: FORMER OWNER WAS: UNIVERSITY TECHNOLOGY CORPORATION |