DK2814473T3 - Pharmaceuticals for combination therapy - Google Patents
Pharmaceuticals for combination therapy Download PDFInfo
- Publication number
- DK2814473T3 DK2814473T3 DK13703834.5T DK13703834T DK2814473T3 DK 2814473 T3 DK2814473 T3 DK 2814473T3 DK 13703834 T DK13703834 T DK 13703834T DK 2814473 T3 DK2814473 T3 DK 2814473T3
- Authority
- DK
- Denmark
- Prior art keywords
- pharmaceutically acceptable
- acceptable salt
- metoprolol
- tesofensin
- tesofensine
- Prior art date
Links
- 239000003814 drug Substances 0.000 title claims description 17
- 238000002648 combination therapy Methods 0.000 title description 14
- 229960002237 metoprolol Drugs 0.000 claims description 77
- IUBSYMUCCVWXPE-UHFFFAOYSA-N metoprolol Chemical compound COCCC1=CC=C(OCC(O)CNC(C)C)C=C1 IUBSYMUCCVWXPE-UHFFFAOYSA-N 0.000 claims description 77
- 150000003839 salts Chemical class 0.000 claims description 74
- 238000011282 treatment Methods 0.000 claims description 55
- 230000000694 effects Effects 0.000 claims description 46
- 208000008589 Obesity Diseases 0.000 claims description 42
- 235000020824 obesity Nutrition 0.000 claims description 42
- 230000002526 effect on cardiovascular system Effects 0.000 claims description 32
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 26
- 208000035475 disorder Diseases 0.000 claims description 21
- 230000002265 prevention Effects 0.000 claims description 20
- 241001465754 Metazoa Species 0.000 claims description 17
- 239000008194 pharmaceutical composition Substances 0.000 claims description 14
- 229940079593 drug Drugs 0.000 claims description 12
- 206010020710 Hyperphagia Diseases 0.000 claims description 8
- 235000020830 overeating Nutrition 0.000 claims description 8
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 6
- 230000001771 impaired effect Effects 0.000 claims description 5
- 201000001320 Atherosclerosis Diseases 0.000 claims description 4
- 206010006550 Bulimia nervosa Diseases 0.000 claims description 4
- 208000032928 Dyslipidaemia Diseases 0.000 claims description 4
- 208000017170 Lipid metabolism disease Diseases 0.000 claims description 4
- 208000001145 Metabolic Syndrome Diseases 0.000 claims description 4
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims description 4
- 239000008186 active pharmaceutical agent Substances 0.000 claims description 4
- 239000002671 adjuvant Substances 0.000 claims description 4
- 208000014679 binge eating disease Diseases 0.000 claims description 4
- 239000000969 carrier Substances 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 239000002552 dosage form Substances 0.000 claims description 3
- 235000021407 appetite control Nutrition 0.000 claims 2
- 235000005686 eating Nutrition 0.000 claims 2
- VCVWXKKWDOJNIT-ZOMKSWQUSA-N tesofensine Chemical compound C1([C@H]2C[C@@H]3CC[C@@H](N3C)[C@@H]2COCC)=CC=C(Cl)C(Cl)=C1 VCVWXKKWDOJNIT-ZOMKSWQUSA-N 0.000 description 165
- 229950009970 tesofensine Drugs 0.000 description 165
- RMMXLENWKUUMAY-UHFFFAOYSA-N telmisartan Chemical compound CCCC1=NC2=C(C)C=C(C=3N(C4=CC=CC=C4N=3)C)C=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C(O)=O RMMXLENWKUUMAY-UHFFFAOYSA-N 0.000 description 36
- 241000700159 Rattus Species 0.000 description 34
- 230000037406 food intake Effects 0.000 description 30
- 235000012631 food intake Nutrition 0.000 description 30
- 239000003981 vehicle Substances 0.000 description 30
- 230000037396 body weight Effects 0.000 description 25
- 239000005537 C09CA07 - Telmisartan Substances 0.000 description 18
- 230000006742 locomotor activity Effects 0.000 description 18
- 229960005187 telmisartan Drugs 0.000 description 18
- 208000016261 weight loss Diseases 0.000 description 18
- 230000036772 blood pressure Effects 0.000 description 16
- 150000001875 compounds Chemical class 0.000 description 15
- 230000001639 hypophagic effect Effects 0.000 description 12
- 238000000034 method Methods 0.000 description 12
- 239000004480 active ingredient Substances 0.000 description 11
- 230000003579 anti-obesity Effects 0.000 description 11
- 238000012544 monitoring process Methods 0.000 description 11
- UNAANXDKBXWMLN-UHFFFAOYSA-N sibutramine Chemical compound C=1C=C(Cl)C=CC=1C1(C(N(C)C)CC(C)C)CCC1 UNAANXDKBXWMLN-UHFFFAOYSA-N 0.000 description 11
- 229960004425 sibutramine Drugs 0.000 description 11
- 230000004580 weight loss Effects 0.000 description 10
- 230000001154 acute effect Effects 0.000 description 9
- 231100000673 dose–response relationship Toxicity 0.000 description 9
- 239000000203 mixture Substances 0.000 description 9
- 230000035488 systolic blood pressure Effects 0.000 description 9
- 239000002220 antihypertensive agent Substances 0.000 description 8
- 230000035487 diastolic blood pressure Effects 0.000 description 8
- 238000009472 formulation Methods 0.000 description 8
- 235000019786 weight gain Nutrition 0.000 description 7
- 108060003345 Adrenergic Receptor Proteins 0.000 description 6
- 102000017910 Adrenergic receptor Human genes 0.000 description 6
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 6
- 230000006870 function Effects 0.000 description 6
- 230000007246 mechanism Effects 0.000 description 6
- 239000002207 metabolite Substances 0.000 description 6
- 206010020772 Hypertension Diseases 0.000 description 5
- 206010063743 Hypophagia Diseases 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 230000009471 action Effects 0.000 description 5
- 230000002411 adverse Effects 0.000 description 5
- 239000000883 anti-obesity agent Substances 0.000 description 5
- 229940030600 antihypertensive agent Drugs 0.000 description 5
- 235000019789 appetite Nutrition 0.000 description 5
- 230000036528 appetite Effects 0.000 description 5
- 238000011278 co-treatment Methods 0.000 description 5
- 238000001647 drug administration Methods 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- 230000002474 noradrenergic effect Effects 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 238000002560 therapeutic procedure Methods 0.000 description 5
- 230000002891 anorexigenic effect Effects 0.000 description 4
- 239000000890 drug combination Substances 0.000 description 4
- 239000003112 inhibitor Substances 0.000 description 4
- 230000001561 neurotransmitter reuptake Effects 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical group C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 230000000638 stimulation Effects 0.000 description 4
- 230000002459 sustained effect Effects 0.000 description 4
- 230000015883 synaptic transmission, dopaminergic Effects 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 241000124008 Mammalia Species 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 229940127088 antihypertensive drug Drugs 0.000 description 3
- 239000002876 beta blocker Substances 0.000 description 3
- 229940097320 beta blocking agent Drugs 0.000 description 3
- 230000001684 chronic effect Effects 0.000 description 3
- 230000001186 cumulative effect Effects 0.000 description 3
- 206010061428 decreased appetite Diseases 0.000 description 3
- 229960003638 dopamine Drugs 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 230000002045 lasting effect Effects 0.000 description 3
- 230000007774 longterm Effects 0.000 description 3
- 230000000422 nocturnal effect Effects 0.000 description 3
- 230000003285 pharmacodynamic effect Effects 0.000 description 3
- 239000000651 prodrug Substances 0.000 description 3
- 229940002612 prodrug Drugs 0.000 description 3
- 230000001603 reducing effect Effects 0.000 description 3
- 235000019627 satiety Nutrition 0.000 description 3
- 230000036186 satiety Effects 0.000 description 3
- 239000013585 weight reducing agent Substances 0.000 description 3
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 108010078791 Carrier Proteins Proteins 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 206010033307 Overweight Diseases 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000002333 angiotensin II receptor antagonist Substances 0.000 description 2
- 239000000400 angiotensin II type 1 receptor blocker Substances 0.000 description 2
- 230000003276 anti-hypertensive effect Effects 0.000 description 2
- 239000002830 appetite depressant Substances 0.000 description 2
- 235000021229 appetite regulation Nutrition 0.000 description 2
- 230000003190 augmentative effect Effects 0.000 description 2
- 230000006399 behavior Effects 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000006583 body weight regulation Effects 0.000 description 2
- 125000002091 cationic group Chemical group 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 230000037149 energy metabolism Effects 0.000 description 2
- 230000004634 feeding behavior Effects 0.000 description 2
- 230000001631 hypertensive effect Effects 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 230000005923 long-lasting effect Effects 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 229940126403 monoamine reuptake inhibitor Drugs 0.000 description 2
- 230000003880 negative regulation of appetite Effects 0.000 description 2
- 230000000966 norepinephrine reuptake Effects 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 230000035807 sensation Effects 0.000 description 2
- 235000019615 sensations Nutrition 0.000 description 2
- 230000001975 sympathomimetic effect Effects 0.000 description 2
- 230000002123 temporal effect Effects 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 230000001960 triggered effect Effects 0.000 description 2
- 239000003174 triple reuptake inhibitor Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical group NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 1
- -1 (7R Chemical compound 0.000 description 1
- WSWCOQWTEOXDQX-MQQKCMAXSA-M (E,E)-sorbate Chemical compound C\C=C\C=C\C([O-])=O WSWCOQWTEOXDQX-MQQKCMAXSA-M 0.000 description 1
- QUIJMHDIAFOPRK-UHFFFAOYSA-N 1-cyclooctylazocane Chemical compound C1CCCCCCC1N1CCCCCCC1 QUIJMHDIAFOPRK-UHFFFAOYSA-N 0.000 description 1
- DGGKXQQCVPAUEA-UHFFFAOYSA-N 8-azabicyclo[3.2.1]octane Chemical compound C1CCC2CCC1N2 DGGKXQQCVPAUEA-UHFFFAOYSA-N 0.000 description 1
- 239000005541 ACE inhibitor Substances 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- JZUFKLXOESDKRF-UHFFFAOYSA-N Chlorothiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O JZUFKLXOESDKRF-UHFFFAOYSA-N 0.000 description 1
- 229920001651 Cyanoacrylate Polymers 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 102000004076 Dopamine D1 Receptors Human genes 0.000 description 1
- 108090000511 Dopamine D1 Receptors Proteins 0.000 description 1
- 108010044266 Dopamine Plasma Membrane Transport Proteins Chemical group 0.000 description 1
- 102000006441 Dopamine Plasma Membrane Transport Proteins Human genes 0.000 description 1
- 206010013710 Drug interaction Diseases 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- AEMRFAOFKBGASW-UHFFFAOYSA-M Glycolate Chemical compound OCC([O-])=O AEMRFAOFKBGASW-UHFFFAOYSA-M 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 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
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 1
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-M Methanesulfonate Chemical compound CS([O-])(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 102000008092 Norepinephrine Plasma Membrane Transport Proteins Human genes 0.000 description 1
- 108010049586 Norepinephrine Plasma Membrane Transport Proteins Proteins 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 229920005372 Plexiglas® Polymers 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 201000004239 Secondary hypertension Diseases 0.000 description 1
- 108010012996 Serotonin Plasma Membrane Transport Proteins Chemical group 0.000 description 1
- 102000019208 Serotonin Plasma Membrane Transport Proteins Human genes 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 239000000150 Sympathomimetic Substances 0.000 description 1
- 206010062119 Sympathomimetic effect Diseases 0.000 description 1
- 208000001871 Tachycardia Diseases 0.000 description 1
- 238000010162 Tukey test Methods 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 210000003489 abdominal muscle Anatomy 0.000 description 1
- 210000003815 abdominal wall Anatomy 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 230000001800 adrenalinergic effect Effects 0.000 description 1
- 239000000674 adrenergic antagonist Substances 0.000 description 1
- 239000000332 adrenergic beta-1 receptor antagonist Substances 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 239000004411 aluminium Substances 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 208000022531 anorexia Diseases 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000001430 anti-depressive effect Effects 0.000 description 1
- 229940125710 antiobesity agent Drugs 0.000 description 1
- 239000000164 antipsychotic agent Substances 0.000 description 1
- 210000000702 aorta abdominal Anatomy 0.000 description 1
- 229940072107 ascorbate Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 238000009530 blood pressure measurement Methods 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 238000007707 calorimetry Methods 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 230000009084 cardiovascular function Effects 0.000 description 1
- 210000000748 cardiovascular system Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 229940114081 cinnamate Drugs 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 229940000425 combination drug Drugs 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000004882 diastolic arterial blood pressure Effects 0.000 description 1
- 150000004683 dihydrates Chemical class 0.000 description 1
- 230000002825 dopamine reuptake Effects 0.000 description 1
- 230000028436 dopamine uptake Effects 0.000 description 1
- 230000003291 dopaminomimetic effect Effects 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 239000000428 dust Substances 0.000 description 1
- 229950005627 embonate Drugs 0.000 description 1
- 229950011470 enantate Drugs 0.000 description 1
- JJJFUHOGVZWXNQ-UHFFFAOYSA-N enbucrilate Chemical compound CCCCOC(=O)C(=C)C#N JJJFUHOGVZWXNQ-UHFFFAOYSA-N 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000000763 evoking effect Effects 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 235000019525 fullness Nutrition 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000005802 health problem Effects 0.000 description 1
- 235000003642 hunger Nutrition 0.000 description 1
- 229960002003 hydrochlorothiazide Drugs 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000002267 hypothalamic effect Effects 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 229960002725 isoflurane Drugs 0.000 description 1
- 238000002350 laparotomy Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 230000003137 locomotive effect Effects 0.000 description 1
- 238000011866 long-term treatment Methods 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-O lysinium(1+) Chemical compound [NH3+]CCCCC([NH3+])C([O-])=O KDXKERNSBIXSRK-UHFFFAOYSA-O 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 150000004682 monohydrates Chemical class 0.000 description 1
- 230000002969 morbid Effects 0.000 description 1
- KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000002767 noradrenalin uptake inhibitor Substances 0.000 description 1
- 229940126569 noradrenaline reuptake inhibitor Drugs 0.000 description 1
- 229960002748 norepinephrine Drugs 0.000 description 1
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 238000001543 one-way ANOVA Methods 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Inorganic materials [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 description 1
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 239000004926 polymethyl methacrylate Substances 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
- 239000000843 powder Substances 0.000 description 1
- IENZQIKPVFGBNW-UHFFFAOYSA-N prazosin Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1=CC=CO1 IENZQIKPVFGBNW-UHFFFAOYSA-N 0.000 description 1
- 229960001289 prazosin Drugs 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 239000003087 receptor blocking agent Substances 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229940076279 serotonin Drugs 0.000 description 1
- 229940126570 serotonin reuptake inhibitor Drugs 0.000 description 1
- 239000003772 serotonin uptake inhibitor Substances 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 229940075554 sorbate Drugs 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 230000002889 sympathetic effect Effects 0.000 description 1
- 230000000946 synaptic effect Effects 0.000 description 1
- 230000001360 synchronised effect Effects 0.000 description 1
- 230000004873 systolic arterial blood pressure Effects 0.000 description 1
- 230000006794 tachycardia Effects 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 150000004685 tetrahydrates Chemical class 0.000 description 1
- 230000035924 thermogenesis Effects 0.000 description 1
- 230000036962 time dependent Effects 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M trans-cinnamate Chemical compound [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 150000004684 trihydrates Chemical class 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 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
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/138—Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine
-
- 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
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/46—8-Azabicyclo [3.2.1] octane; Derivatives thereof, e.g. atropine, cocaine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- 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
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Landscapes
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Emergency Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Endocrinology (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Child & Adolescent Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261599623P | 2012-02-16 | 2012-02-16 | |
| DKPA201270076 | 2012-02-16 | ||
| PCT/EP2013/052941 WO2013120935A1 (en) | 2012-02-16 | 2013-02-14 | Pharmaceutical compositions for combination therapy |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DK2814473T3 true DK2814473T3 (en) | 2019-01-28 |
Family
ID=48983571
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK13703834.5T DK2814473T3 (en) | 2012-02-16 | 2013-02-14 | Pharmaceuticals for combination therapy |
Country Status (14)
| Country | Link |
|---|---|
| US (5) | US9211271B2 (enExample) |
| EP (1) | EP2814473B1 (enExample) |
| JP (1) | JP6203760B2 (enExample) |
| CN (3) | CN104244935A (enExample) |
| AU (1) | AU2013220424B2 (enExample) |
| CA (1) | CA2864264C (enExample) |
| DK (1) | DK2814473T3 (enExample) |
| EA (1) | EA029543B1 (enExample) |
| ES (1) | ES2704987T3 (enExample) |
| HR (1) | HRP20190050T1 (enExample) |
| LT (1) | LT2814473T (enExample) |
| PL (1) | PL2814473T3 (enExample) |
| SI (1) | SI2814473T1 (enExample) |
| WO (1) | WO2013120935A1 (enExample) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EA029543B1 (ru) * | 2012-02-16 | 2018-04-30 | Саниона А/С | Способ лечения, профилактики или уменьшения сердечно-сосудистых побочных эффектов тезофенсина |
| KR101839396B1 (ko) * | 2013-12-28 | 2018-03-16 | 인텔 코포레이션 | 주변 디바이스들에서의 센서들로부터의 사용자 컨텍스트 검출에 기초한 디바이스 액션 및 구성을 위한 시스템 및 방법 |
| AU2016228002B2 (en) | 2015-03-03 | 2020-10-01 | Saniona A/S | Tesofensine, beta blocker combination formulation |
| US20190060301A1 (en) | 2016-01-15 | 2019-02-28 | Saniona A/S | Tesofensine and metoprolol for treatment of hypertension |
| CR20190142A (es) | 2016-09-07 | 2019-05-22 | Saniona As | Composiciones de tesofensina |
| WO2020144146A1 (en) | 2019-01-07 | 2020-07-16 | Saniona A/S | Tesofensine for reduction of body weight in prader-willi patients |
| CN110297826B (zh) * | 2019-05-31 | 2020-12-11 | 南京理工大学 | 基于json动态解析卫星遥测数据的方法 |
| JP7784144B2 (ja) | 2020-04-22 | 2025-12-11 | サニオナ エー／エス | 視床下部性肥満症の処置 |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2093833T3 (es) * | 1991-03-18 | 1997-01-01 | Sepracor Inc | Composicion y metodo que contiene (s)-metoprolol opticamente puro. |
| WO1997030997A1 (en) | 1996-02-22 | 1997-08-28 | Neurosearch A/S | Tropane-derivatives, their preparation and use |
| EP1727547A1 (en) | 2004-01-22 | 2006-12-06 | Neurosearch A/S | Compounds for the sustained reduction of body weight |
| EP2222302A1 (en) | 2007-11-20 | 2010-09-01 | NeuroSearch A/S | A method for treating over-eating disorders |
| WO2009080691A2 (en) | 2007-12-20 | 2009-07-02 | Neurosearch A/S | Pharmaceutical composition comprising tesofensine or its analogue and an anti-obesity compound |
| WO2009080693A2 (en) | 2007-12-20 | 2009-07-02 | Neurosearch A/S | Pharmaceutical composition comprising tesofensine or its analogue and a beta blocker |
| US9408837B2 (en) * | 2008-05-28 | 2016-08-09 | Kitov Pharmaceutical Ltd. | Ameliorating drug-induced elevations in blood pressure by adjunctive use of antihypertensive drugs |
| EA029543B1 (ru) * | 2012-02-16 | 2018-04-30 | Саниона А/С | Способ лечения, профилактики или уменьшения сердечно-сосудистых побочных эффектов тезофенсина |
| AU2016228002B2 (en) * | 2015-03-03 | 2020-10-01 | Saniona A/S | Tesofensine, beta blocker combination formulation |
-
2013
- 2013-02-14 EA EA201491532A patent/EA029543B1/ru not_active IP Right Cessation
- 2013-02-14 DK DK13703834.5T patent/DK2814473T3/en active
- 2013-02-14 WO PCT/EP2013/052941 patent/WO2013120935A1/en not_active Ceased
- 2013-02-14 CA CA2864264A patent/CA2864264C/en active Active
- 2013-02-14 SI SI201331313T patent/SI2814473T1/sl unknown
- 2013-02-14 CN CN201380020405.5A patent/CN104244935A/zh active Pending
- 2013-02-14 CN CN201810575583.9A patent/CN108434129A/zh active Pending
- 2013-02-14 EP EP13703834.5A patent/EP2814473B1/en active Active
- 2013-02-14 HR HRP20190050TT patent/HRP20190050T1/hr unknown
- 2013-02-14 LT LTEP13703834.5T patent/LT2814473T/lt unknown
- 2013-02-14 JP JP2014557034A patent/JP6203760B2/ja active Active
- 2013-02-14 US US14/379,032 patent/US9211271B2/en active Active
- 2013-02-14 PL PL13703834T patent/PL2814473T3/pl unknown
- 2013-02-14 AU AU2013220424A patent/AU2013220424B2/en not_active Ceased
- 2013-02-14 ES ES13703834T patent/ES2704987T3/es active Active
- 2013-02-14 CN CN201810580312.2A patent/CN108853071A/zh active Pending
-
2015
- 2015-11-10 US US14/936,963 patent/US9387184B2/en active Active
-
2016
- 2016-07-11 US US15/206,477 patent/US20170007557A1/en not_active Abandoned
-
2018
- 2018-02-27 US US15/906,350 patent/US20180185304A1/en not_active Abandoned
-
2021
- 2021-07-27 US US17/386,098 patent/US20220016055A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| HK1204946A1 (en) | 2015-12-11 |
| CA2864264A1 (en) | 2013-08-22 |
| US9211271B2 (en) | 2015-12-15 |
| EP2814473A1 (en) | 2014-12-24 |
| US20180185304A1 (en) | 2018-07-05 |
| US20160074344A1 (en) | 2016-03-17 |
| LT2814473T (lt) | 2019-01-25 |
| ES2704987T3 (es) | 2019-03-21 |
| HRP20190050T1 (hr) | 2019-03-08 |
| CN108434129A (zh) | 2018-08-24 |
| US9387184B2 (en) | 2016-07-12 |
| EP2814473B1 (en) | 2018-10-10 |
| SI2814473T1 (sl) | 2019-03-29 |
| EA201491532A1 (ru) | 2015-01-30 |
| US20170007557A1 (en) | 2017-01-12 |
| PL2814473T3 (pl) | 2019-06-28 |
| JP6203760B2 (ja) | 2017-09-27 |
| CN108853071A (zh) | 2018-11-23 |
| AU2013220424B2 (en) | 2017-03-23 |
| CA2864264C (en) | 2020-05-05 |
| CN104244935A (zh) | 2014-12-24 |
| EA029543B1 (ru) | 2018-04-30 |
| US20150025107A1 (en) | 2015-01-22 |
| WO2013120935A1 (en) | 2013-08-22 |
| JP2015508765A (ja) | 2015-03-23 |
| US20220016055A1 (en) | 2022-01-20 |
| AU2013220424A1 (en) | 2014-09-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20220016055A1 (en) | Pharmaceutical Compositions For Combination Therapy | |
| US9901568B2 (en) | Pharmaceutical compositions of 5-hydroxytryptophan and serotonin-enhancing compound | |
| JP5203373B2 (ja) | 痛みの治療のための混合されたＯＲＬ１／μ−アゴニスト | |
| WO2011107583A1 (en) | Substituted 4-phenyl-n-alkyl-piperidines for preventing onset or slowing progression of neurodegenerative disorders | |
| US20160256449A1 (en) | H3 receptor antagonist for use in the treatment of alzheimer's disease | |
| Bentzen et al. | Anti‐hypertensive treatment preserves appetite suppression while preventing cardiovascular adverse effects of tesofensine in rats | |
| AU2005205880B2 (en) | Compounds for the sustained reduction of body weight | |
| HK1204946B (en) | Pharmaceutical compositions for combination therapy | |
| WO2023086433A1 (en) | Methods and compositions for treating conditions associated with central hypoventilation | |
| CN102858339B (zh) | 用于治疗疼痛的血清素和去甲肾上腺素再摄取抑制剂与类鸦片激动剂的组合 | |
| WO2009080693A2 (en) | Pharmaceutical composition comprising tesofensine or its analogue and a beta blocker | |
| CA2946270A1 (en) | Drug for treatment of tinnitus patients |