SK6442003A3 - Novel use of combined 5-HT1A agonists and selective serotonin reuptake inhibitors - Google Patents
Novel use of combined 5-HT1A agonists and selective serotonin reuptake inhibitors Download PDFInfo
- Publication number
- SK6442003A3 SK6442003A3 SK644-2003A SK6442003A SK6442003A3 SK 6442003 A3 SK6442003 A3 SK 6442003A3 SK 6442003 A SK6442003 A SK 6442003A SK 6442003 A3 SK6442003 A3 SK 6442003A3
- Authority
- SK
- Slovakia
- Prior art keywords
- pain
- butyl
- physiologically acceptable
- treatment
- serotonin
- Prior art date
Links
- 102100022738 5-hydroxytryptamine receptor 1A Human genes 0.000 title claims abstract description 31
- 101710138638 5-hydroxytryptamine receptor 1A Proteins 0.000 title claims abstract description 31
- 229940124834 selective serotonin reuptake inhibitor Drugs 0.000 title claims description 31
- 239000012896 selective serotonin reuptake inhibitor Substances 0.000 title claims description 27
- 239000000556 agonist Substances 0.000 title description 3
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 claims abstract description 140
- 208000002193 Pain Diseases 0.000 claims abstract description 96
- 150000003839 salts Chemical class 0.000 claims abstract description 57
- 238000011282 treatment Methods 0.000 claims abstract description 48
- 229940076279 serotonin Drugs 0.000 claims abstract description 35
- 239000000018 receptor agonist Substances 0.000 claims abstract description 34
- 229940044601 receptor agonist Drugs 0.000 claims abstract description 34
- 150000001875 compounds Chemical class 0.000 claims abstract description 33
- 208000000094 Chronic Pain Diseases 0.000 claims abstract description 29
- 239000003814 drug Substances 0.000 claims abstract description 22
- BPSWBRVXRVOQSP-UHFFFAOYSA-N 3-[4-[4-(4-cyanophenyl)piperazin-1-yl]butyl]-1h-indole-5-carbonitrile Chemical compound C1=CC(C#N)=CC=C1N1CCN(CCCCC=2C3=CC(=CC=C3NC=2)C#N)CC1 BPSWBRVXRVOQSP-UHFFFAOYSA-N 0.000 claims abstract description 20
- 208000002551 irritable bowel syndrome Diseases 0.000 claims abstract description 20
- 238000004519 manufacturing process Methods 0.000 claims abstract description 19
- SGEGOXDYSFKCPT-UHFFFAOYSA-N vilazodone Chemical compound C1=C(C#N)C=C2C(CCCCN3CCN(CC3)C=3C=C4C=C(OC4=CC=3)C(=O)N)=CNC2=C1 SGEGOXDYSFKCPT-UHFFFAOYSA-N 0.000 claims abstract description 19
- 229940124639 Selective inhibitor Drugs 0.000 claims description 30
- -1 5-cyanindol-3-yl Chemical group 0.000 claims description 20
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 13
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- PAXIQTUHSUQLAD-UHFFFAOYSA-N C(#N)C1=CC=C(C=C1)N1CCN(CC1)CCCCC1=CNC2=CC=C(C=C12)C#N.Cl.C(#N)C1=CC=C(C=C1)N1CCN(CC1)CCCCC1=CNC2=CC=C(C=C12)C#N Chemical compound C(#N)C1=CC=C(C=C1)N1CCN(CC1)CCCCC1=CNC2=CC=C(C=C12)C#N.Cl.C(#N)C1=CC=C(C=C1)N1CCN(CC1)CCCCC1=CNC2=CC=C(C=C12)C#N PAXIQTUHSUQLAD-UHFFFAOYSA-N 0.000 claims description 3
- YHYLDEVWYOFIJK-UHFFFAOYSA-N 1h-indole-5-carbonitrile Chemical compound N#CC1=CC=C2NC=CC2=C1 YHYLDEVWYOFIJK-UHFFFAOYSA-N 0.000 claims 1
- CVVIJWRCGSYCMB-UHFFFAOYSA-N hydron;piperazine;dichloride Chemical compound Cl.Cl.C1CNCCN1 CVVIJWRCGSYCMB-UHFFFAOYSA-N 0.000 claims 1
- 230000036407 pain Effects 0.000 abstract description 63
- 208000004454 Hyperalgesia Diseases 0.000 abstract description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 7
- 208000035475 disorder Diseases 0.000 abstract description 6
- 239000003112 inhibitor Substances 0.000 abstract description 5
- 208000035154 Hyperesthesia Diseases 0.000 abstract description 4
- 206010053552 allodynia Diseases 0.000 abstract description 4
- 230000037324 pain perception Effects 0.000 abstract description 2
- 206010070834 Sensitisation Diseases 0.000 abstract 1
- 241000700159 Rattus Species 0.000 description 35
- 241001465754 Metazoa Species 0.000 description 25
- 238000012360 testing method Methods 0.000 description 25
- 230000035939 shock Effects 0.000 description 18
- 241000699670 Mus sp. Species 0.000 description 15
- 208000004296 neuralgia Diseases 0.000 description 14
- 210000002683 foot Anatomy 0.000 description 12
- 206010019233 Headaches Diseases 0.000 description 11
- 231100000869 headache Toxicity 0.000 description 11
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 10
- 230000000638 stimulation Effects 0.000 description 10
- 230000037396 body weight Effects 0.000 description 9
- 238000000034 method Methods 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 8
- 101000629937 Homo sapiens Translocon-associated protein subunit alpha Proteins 0.000 description 8
- 102100026231 Translocon-associated protein subunit alpha Human genes 0.000 description 8
- 208000001294 Nociceptive Pain Diseases 0.000 description 7
- 229920005372 Plexiglas® Polymers 0.000 description 7
- 210000000548 hind-foot Anatomy 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- 208000021722 neuropathic pain Diseases 0.000 description 7
- 230000005855 radiation Effects 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 208000027418 Wounds and injury Diseases 0.000 description 6
- 239000002671 adjuvant Substances 0.000 description 6
- 239000007924 injection Substances 0.000 description 6
- 238000002347 injection Methods 0.000 description 6
- 230000004044 response Effects 0.000 description 6
- 208000011580 syndromic disease Diseases 0.000 description 6
- 206010065390 Inflammatory pain Diseases 0.000 description 5
- 208000006011 Stroke Diseases 0.000 description 5
- 230000001684 chronic effect Effects 0.000 description 5
- 230000006378 damage Effects 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 230000004054 inflammatory process Effects 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 239000000546 pharmaceutical excipient Substances 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- 206010061218 Inflammation Diseases 0.000 description 4
- 208000004550 Postoperative Pain Diseases 0.000 description 4
- 206010036618 Premenstrual syndrome Diseases 0.000 description 4
- 208000005298 acute pain Diseases 0.000 description 4
- 206010008118 cerebral infarction Diseases 0.000 description 4
- 208000014674 injury Diseases 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 239000004926 polymethyl methacrylate Substances 0.000 description 4
- 239000000523 sample Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- QHKJIJXBJCOABP-UHFFFAOYSA-N 1-benzofuran-2-carboxamide Chemical compound C1=CC=C2OC(C(=O)N)=CC2=C1 QHKJIJXBJCOABP-UHFFFAOYSA-N 0.000 description 3
- RLQZIECDMISZHS-UHFFFAOYSA-N 2-phenylcyclohexa-2,5-diene-1,4-dione Chemical compound O=C1C=CC(=O)C(C=2C=CC=CC=2)=C1 RLQZIECDMISZHS-UHFFFAOYSA-N 0.000 description 3
- 208000008035 Back Pain Diseases 0.000 description 3
- 208000020401 Depressive disease Diseases 0.000 description 3
- 208000032131 Diabetic Neuropathies Diseases 0.000 description 3
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 3
- 208000019695 Migraine disease Diseases 0.000 description 3
- 208000004983 Phantom Limb Diseases 0.000 description 3
- 206010056238 Phantom pain Diseases 0.000 description 3
- 208000028017 Psychotic disease Diseases 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 230000000202 analgesic effect Effects 0.000 description 3
- 230000003110 anti-inflammatory effect Effects 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 239000012154 double-distilled water Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 206010027599 migraine Diseases 0.000 description 3
- 230000003040 nociceptive effect Effects 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 230000001107 psychogenic effect Effects 0.000 description 3
- 239000003723 serotonin 1A agonist Substances 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000007921 spray Substances 0.000 description 3
- 238000001356 surgical procedure Methods 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 239000000454 talc Substances 0.000 description 3
- 229910052623 talc Inorganic materials 0.000 description 3
- 230000000451 tissue damage Effects 0.000 description 3
- 231100000827 tissue damage Toxicity 0.000 description 3
- RPZBRGFNBNQSOP-UHFFFAOYSA-N vilazodone hydrochloride Chemical class Cl.C1=C(C#N)C=C2C(CCCCN3CCN(CC3)C=3C=C4C=C(OC4=CC=3)C(=O)N)=CNC2=C1 RPZBRGFNBNQSOP-UHFFFAOYSA-N 0.000 description 3
- 208000009935 visceral pain Diseases 0.000 description 3
- 206010000599 Acromegaly Diseases 0.000 description 2
- 206010049589 Afterbirth pain Diseases 0.000 description 2
- 201000000736 Amenorrhea Diseases 0.000 description 2
- 206010001928 Amenorrhoea Diseases 0.000 description 2
- 206010002383 Angina Pectoris Diseases 0.000 description 2
- 201000006474 Brain Ischemia Diseases 0.000 description 2
- 206010058019 Cancer Pain Diseases 0.000 description 2
- 208000018152 Cerebral disease Diseases 0.000 description 2
- 206010008120 Cerebral ischaemia Diseases 0.000 description 2
- 208000018380 Chemical injury Diseases 0.000 description 2
- 208000017667 Chronic Disease Diseases 0.000 description 2
- 206010063057 Cystitis noninfective Diseases 0.000 description 2
- 206010020751 Hypersensitivity Diseases 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- 206010058359 Hypogonadism Diseases 0.000 description 2
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 206010033892 Paraplegia Diseases 0.000 description 2
- 208000000450 Pelvic Pain Diseases 0.000 description 2
- 206010036376 Postherpetic Neuralgia Diseases 0.000 description 2
- 206010065347 Premenstrual pain Diseases 0.000 description 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 2
- 208000008765 Sciatica Diseases 0.000 description 2
- 206010042496 Sunburn Diseases 0.000 description 2
- 208000003827 Vulvar Vestibulitis Diseases 0.000 description 2
- 208000026935 allergic disease Diseases 0.000 description 2
- 231100000540 amenorrhea Toxicity 0.000 description 2
- 239000003708 ampul Substances 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 208000015114 central nervous system disease Diseases 0.000 description 2
- 208000026106 cerebrovascular disease Diseases 0.000 description 2
- 208000037976 chronic inflammation Diseases 0.000 description 2
- 230000002920 convulsive effect Effects 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 2
- 239000008298 dragée Substances 0.000 description 2
- 238000001647 drug administration Methods 0.000 description 2
- 238000003255 drug test Methods 0.000 description 2
- 230000029142 excretion Effects 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 230000009610 hypersensitivity Effects 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 230000000968 intestinal effect Effects 0.000 description 2
- 230000006651 lactation Effects 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- 210000000653 nervous system Anatomy 0.000 description 2
- 230000002981 neuropathic effect Effects 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 230000008533 pain sensitivity Effects 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 235000019271 petrolatum Nutrition 0.000 description 2
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 2
- 150000004885 piperazines Chemical class 0.000 description 2
- 229920001592 potato starch Polymers 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000011321 prophylaxis Methods 0.000 description 2
- 230000009103 reabsorption Effects 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 230000000392 somatic effect Effects 0.000 description 2
- 235000012222 talc Nutrition 0.000 description 2
- 238000004448 titration Methods 0.000 description 2
- 208000004371 toothache Diseases 0.000 description 2
- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- ZEUITGRIYCTCEM-KRWDZBQOSA-N (S)-duloxetine Chemical compound C1([C@@H](OC=2C3=CC=CC=C3C=CC=2)CCNC)=CC=CS1 ZEUITGRIYCTCEM-KRWDZBQOSA-N 0.000 description 1
- OOSZCNKVJAVHJI-UHFFFAOYSA-N 1-[(4-fluorophenyl)methyl]piperazine Chemical compound C1=CC(F)=CC=C1CN1CCNCC1 OOSZCNKVJAVHJI-UHFFFAOYSA-N 0.000 description 1
- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 description 1
- LLRGOAFFRRUFBM-UHFFFAOYSA-N 5-piperazin-1-yl-1-benzofuran-2-carboxamide Chemical compound C=1C=C2OC(C(=O)N)=CC2=CC=1N1CCNCC1 LLRGOAFFRRUFBM-UHFFFAOYSA-N 0.000 description 1
- 208000004998 Abdominal Pain Diseases 0.000 description 1
- 241001535291 Analges Species 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 241001598984 Bromius obscurus Species 0.000 description 1
- KERRETXUDOVMPI-UHFFFAOYSA-N C(#N)C1=CC=C(C=C1)N1CCN(CC1)CCCCC1=C2C=CNC2=CC=C1C#N Chemical compound C(#N)C1=CC=C(C=C1)N1CCN(CC1)CCCCC1=C2C=CNC2=CC=C1C#N KERRETXUDOVMPI-UHFFFAOYSA-N 0.000 description 1
- 206010008190 Cerebrovascular accident Diseases 0.000 description 1
- YRPSYMPXZZARHV-UHFFFAOYSA-N Cl.N#Cc1ccc2[nH]ccc2c1 Chemical compound Cl.N#Cc1ccc2[nH]ccc2c1 YRPSYMPXZZARHV-UHFFFAOYSA-N 0.000 description 1
- 206010010774 Constipation Diseases 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 208000001375 Facial Neuralgia Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 206010020843 Hyperthermia Diseases 0.000 description 1
- 208000007914 Labor Pain Diseases 0.000 description 1
- 208000035945 Labour pain Diseases 0.000 description 1
- 241000551546 Minerva Species 0.000 description 1
- 241000186359 Mycobacterium Species 0.000 description 1
- 206010028836 Neck pain Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 206010036030 Polyarthritis Diseases 0.000 description 1
- 208000025747 Rheumatic disease Diseases 0.000 description 1
- 206010061363 Skeletal injury Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 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 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- CJCSPKMFHVPWAR-JTQLQIEISA-N alpha-methyl-L-dopa Chemical compound OC(=O)[C@](N)(C)CC1=CC=C(O)C(O)=C1 CJCSPKMFHVPWAR-JTQLQIEISA-N 0.000 description 1
- 238000002266 amputation Methods 0.000 description 1
- 230000003070 anti-hyperalgesia Effects 0.000 description 1
- 230000007234 antiinflammatory process Effects 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 101150024767 arnT gene Proteins 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 238000007675 cardiac surgery Methods 0.000 description 1
- 239000000679 carrageenan Substances 0.000 description 1
- 235000010418 carrageenan Nutrition 0.000 description 1
- 229920001525 carrageenan Polymers 0.000 description 1
- 229940113118 carrageenan Drugs 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000006020 chronic inflammation Effects 0.000 description 1
- 208000022371 chronic pain syndrome Diseases 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 229940051068 counteract pain Drugs 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 125000004802 cyanophenyl group Chemical group 0.000 description 1
- 230000000881 depressing effect Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 229910000397 disodium phosphate Inorganic materials 0.000 description 1
- 235000019800 disodium phosphate Nutrition 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 229960002866 duloxetine Drugs 0.000 description 1
- 230000002996 emotional effect Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 230000001815 facial effect Effects 0.000 description 1
- 206010016766 flatulence Diseases 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 235000013773 glyceryl triacetate Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- MSQACBWWAIBWIC-UHFFFAOYSA-N hydron;piperazine;chloride Chemical compound Cl.C1CNCCN1 MSQACBWWAIBWIC-UHFFFAOYSA-N 0.000 description 1
- 230000036031 hyperthermia Effects 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- YWXYYJSYQOXTPL-SLPGGIOYSA-N isosorbide mononitrate Chemical compound [O-][N+](=O)O[C@@H]1CO[C@@H]2[C@@H](O)CO[C@@H]21 YWXYYJSYQOXTPL-SLPGGIOYSA-N 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 230000001272 neurogenic effect Effects 0.000 description 1
- 239000000014 opioid analgesic Substances 0.000 description 1
- 229940005483 opioid analgesics Drugs 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 239000008196 pharmacological composition Substances 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 208000030428 polyarticular arthritis Diseases 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- 230000026416 response to pain Effects 0.000 description 1
- 230000000552 rheumatic effect Effects 0.000 description 1
- 201000000980 schizophrenia Diseases 0.000 description 1
- 230000035807 sensation Effects 0.000 description 1
- 230000000697 serotonin reuptake Effects 0.000 description 1
- 230000013275 serotonin uptake Effects 0.000 description 1
- 208000018316 severe headache Diseases 0.000 description 1
- 229940074545 sodium dihydrogen phosphate dihydrate Drugs 0.000 description 1
- 239000008347 soybean phospholipid Substances 0.000 description 1
- 210000001032 spinal nerve Anatomy 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000007940 sugar coated tablet Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 229960002622 triacetin Drugs 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 230000009278 visceral effect Effects 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- 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
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Pain & Pain Management (AREA)
- Biomedical Technology (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP00125409 | 2000-11-20 | ||
| PCT/EP2001/012686 WO2002039989A1 (en) | 2000-11-20 | 2001-11-02 | Novel use of combined 5-ht1a agonists and selective serotonin reuptake inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| SK6442003A3 true SK6442003A3 (en) | 2003-09-11 |
Family
ID=8170432
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK644-2003A SK6442003A3 (en) | 2000-11-20 | 2001-11-02 | Novel use of combined 5-HT1A agonists and selective serotonin reuptake inhibitors |
Country Status (19)
| Country | Link |
|---|---|
| US (1) | US7479492B2 (zh) |
| EP (1) | EP1335716A1 (zh) |
| JP (1) | JP2004513916A (zh) |
| KR (1) | KR20030048477A (zh) |
| CN (1) | CN1541093A (zh) |
| AR (1) | AR031463A1 (zh) |
| AU (2) | AU2180302A (zh) |
| BR (1) | BR0115434A (zh) |
| CA (1) | CA2429216C (zh) |
| CZ (1) | CZ20031448A3 (zh) |
| HU (1) | HUP0400504A3 (zh) |
| MX (1) | MXPA03004341A (zh) |
| NO (1) | NO20032248D0 (zh) |
| PL (1) | PL361617A1 (zh) |
| RU (1) | RU2302243C2 (zh) |
| SK (1) | SK6442003A3 (zh) |
| UA (1) | UA76130C2 (zh) |
| WO (1) | WO2002039989A1 (zh) |
| ZA (1) | ZA200304757B (zh) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE10326939A1 (de) * | 2003-06-16 | 2005-01-05 | Merck Patent Gmbh | Indol-Derivate |
| EP1732610A2 (en) | 2004-03-26 | 2006-12-20 | Baylor University | Targeted serotonin reuptake inhibitors |
| WO2006006152A2 (en) * | 2004-07-08 | 2006-01-19 | Ramot At Tel-Aviv University Ltd | Treatment of disorders and diseases of the colon |
| US7994331B2 (en) | 2005-07-13 | 2011-08-09 | Msd K.K. | Heterocycle-substituted benzimidazole derivative |
| EP2044043B2 (en) | 2006-06-16 | 2021-03-03 | H. Lundbeck A/S | 1- ý[- (2, 4-dimethylphenylsulfanyl) -phenyl]piperazine hydrobromide as a compound with combined serotonin reuptake, 5-ht3 and 5-ht1a activity for the treatment of cognitive impairment |
| TW200848411A (en) * | 2007-03-20 | 2008-12-16 | Lundbeck & Co As H | Novel therapeutic uses of 1-[2-(2, 4-dimethylphenylsulfanyl)phenyl]-piperazine |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2222768B (en) * | 1988-06-17 | 1992-01-22 | Nat Res Dev | Analgesic compounds and compositions |
| US5589511A (en) * | 1990-08-13 | 1996-12-31 | Sepracor Inc. | Method for treating migraine headaches using optically pure S(+) fluoxetine |
| US5578612A (en) * | 1990-10-15 | 1996-11-26 | Pfizer Inc. | Indole derivatives |
| US5434174A (en) * | 1992-07-17 | 1995-07-18 | Eli Lilly And Company | Isoxazole derivatives for the treatment of irritable bowel syndrome |
| DE4333254A1 (de) * | 1993-09-30 | 1995-04-06 | Merck Patent Gmbh | Piperidine und Piperazine |
| US5576321A (en) * | 1995-01-17 | 1996-11-19 | Eli Lilly And Company | Compounds having effects on serotonin-related systems |
| DE19512639A1 (de) * | 1995-04-05 | 1996-10-10 | Merck Patent Gmbh | Benzonitrile und -fluoride |
| US5912256A (en) * | 1996-06-20 | 1999-06-15 | Eli Lilly And Company | Compounds having effects on serotonin-related systems |
| UA56185C2 (uk) * | 1996-09-30 | 2003-05-15 | Пфайзер Інк. | Аралкіл- та аралкіліденгетероциклічні лактами та іміди, фармацевтична композиція та спосіб лікування |
| GB9911863D0 (en) * | 1999-05-21 | 1999-07-21 | Knoll Ag | Therapeutic agents |
| TW518218B (en) | 1999-05-27 | 2003-01-21 | Merck Patent Gmbh | Pharmaceutical compositions comprising 1-[4-(5-cyanoindol-3-yl)butyl]-4-(2-carbamoylbenzofuran-5-yl)piperazine or its physiologically acceptable salts for use in the treatment of sub-type anxiety disorders |
-
2001
- 2001-02-11 UA UA2003065609A patent/UA76130C2/uk unknown
- 2001-11-02 CN CNA018191118A patent/CN1541093A/zh active Pending
- 2001-11-02 EP EP01996368A patent/EP1335716A1/en not_active Ceased
- 2001-11-02 BR BR0115434-6A patent/BR0115434A/pt not_active Application Discontinuation
- 2001-11-02 AU AU2180302A patent/AU2180302A/xx active Pending
- 2001-11-02 AU AU2002221803A patent/AU2002221803B2/en not_active Ceased
- 2001-11-02 RU RU2003116893/15A patent/RU2302243C2/ru not_active IP Right Cessation
- 2001-11-02 PL PL36161701A patent/PL361617A1/xx not_active Application Discontinuation
- 2001-11-02 HU HU0400504A patent/HUP0400504A3/hu unknown
- 2001-11-02 JP JP2002542364A patent/JP2004513916A/ja active Pending
- 2001-11-02 CA CA2429216A patent/CA2429216C/en not_active Expired - Fee Related
- 2001-11-02 CZ CZ20031448A patent/CZ20031448A3/cs unknown
- 2001-11-02 KR KR10-2003-7006755A patent/KR20030048477A/ko not_active Application Discontinuation
- 2001-11-02 MX MXPA03004341A patent/MXPA03004341A/es active IP Right Grant
- 2001-11-02 WO PCT/EP2001/012686 patent/WO2002039989A1/en not_active Application Discontinuation
- 2001-11-02 SK SK644-2003A patent/SK6442003A3/sk not_active Application Discontinuation
- 2001-11-02 US US10/432,047 patent/US7479492B2/en not_active Expired - Lifetime
- 2001-11-16 AR ARP010105360A patent/AR031463A1/es unknown
-
2003
- 2003-05-19 NO NO20032248A patent/NO20032248D0/no unknown
- 2003-06-19 ZA ZA200304757A patent/ZA200304757B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CA2429216C (en) | 2012-08-07 |
| NO20032248L (no) | 2003-05-19 |
| JP2004513916A (ja) | 2004-05-13 |
| AU2180302A (en) | 2002-05-27 |
| PL361617A1 (en) | 2004-10-04 |
| ZA200304757B (en) | 2004-09-20 |
| HUP0400504A3 (en) | 2006-02-28 |
| RU2302243C2 (ru) | 2007-07-10 |
| CN1541093A (zh) | 2004-10-27 |
| KR20030048477A (ko) | 2003-06-19 |
| AU2002221803B2 (en) | 2007-02-15 |
| NO20032248D0 (no) | 2003-05-19 |
| AR031463A1 (es) | 2003-09-24 |
| HUP0400504A2 (hu) | 2004-06-28 |
| UA76130C2 (en) | 2006-07-17 |
| MXPA03004341A (es) | 2003-08-19 |
| BR0115434A (pt) | 2003-10-07 |
| CA2429216A1 (en) | 2002-05-23 |
| CZ20031448A3 (cs) | 2003-09-17 |
| US20040014771A1 (en) | 2004-01-22 |
| WO2002039989A1 (en) | 2002-05-23 |
| EP1335716A1 (en) | 2003-08-20 |
| US7479492B2 (en) | 2009-01-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US7569604B2 (en) | Heterocyclic derivatives for modulation of calcium channels | |
| DE60017115T2 (de) | Amid-derivate und deren medizinische verwendung | |
| EP1736158B1 (en) | Use of 1- 4-(5-cyanoindol-3-yl)butyl -4-(2-carbamoylbenzofuran-5-yl)piperazine and its physiologically acceptable salts | |
| EP0977558B1 (en) | Use of 5ht4 receptor antagonists for overcoming gastrointestinal effects of serotonin reuptake inhibitors | |
| KR20090125251A (ko) | 수면 및 인지 관련 우울증에서의 통증 또는 잔여 증상의 치료를 위한, 세로토닌 재흡수, ５-ｈｔ３ 및 ５-ｈｔ１ａ 활성을 갖는 화합물인 1-[2-(2,4-디메틸페닐술파닐)페닐]피페라진 | |
| JP5453258B2 (ja) | カンナビノイド受容体の複素環式モジュレーター | |
| HU226976B1 (en) | Use of pirrolidine derivatives having kappa-opium-agonist effect for the preparation of a medicament for treating of inflammatory diseases of the intestine | |
| HRP20010473A2 (en) | Combination chemotherapy | |
| TW201536295A (zh) | σ配體在與間質性膀胱炎／膀胱疼痛綜合徵（ＩＣ／ＢＰＳ）相關的疼痛的預防和治療中的應用 | |
| US20220008414A1 (en) | Pharmaceutical composition comprising histone deacetylase 6 inhibitors | |
| US5236942A (en) | 5-aryl-4-alkyl-3H-1,2,4-triazole-3-thiones useful in the treatment of Altzheimer's dementia | |
| SK6442003A3 (en) | Novel use of combined 5-HT1A agonists and selective serotonin reuptake inhibitors | |
| US5100906A (en) | 5-aryl-4-alkyl-3h-1,2,4-triazole-3-thiones useful as memory enhancers | |
| WO1995031988A1 (en) | COMPOSITION CONTAINING 5HTIA and 5HTID ANTAGONISTS | |
| AU2002221803A1 (en) | Novel use of combined 5-HT1A agonists and selective serotonin reuptake inhibitors | |
| US5331002A (en) | 5-aryl-4-alkyl-3H-1,2,4-triazole-3-thiones useful as memory enhancers | |
| ZA200503520B (en) | Use of 5-HT2 receptor antagonists for the treatment of sleep disorders. | |
| CA2351674A1 (en) | Use of a 5ht2a and 5ht2a/c receptor antagonist for preparing medicines for treating snoring and high resistance syndrome of upper anatomical airways | |
| NZ539797A (en) | Use of 5-HT2 receptor antagonists for the treatment of sleep disorders |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FC9A | Refused patent application |