CA2321728C - Epiallopregnanolone in the treatment of cns disorders - Google Patents
Epiallopregnanolone in the treatment of cns disorders Download PDFInfo
- Publication number
- CA2321728C CA2321728C CA002321728A CA2321728A CA2321728C CA 2321728 C CA2321728 C CA 2321728C CA 002321728 A CA002321728 A CA 002321728A CA 2321728 A CA2321728 A CA 2321728A CA 2321728 C CA2321728 C CA 2321728C
- Authority
- CA
- Canada
- Prior art keywords
- hydroxy
- 5alpha
- pregnan
- 3beta
- steroids
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- AURFZBICLPNKBZ-FZCSVUEKSA-N 3beta-hydroxy-5alpha-pregnan-20-one Chemical compound C([C@@H]1CC2)[C@@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](C(=O)C)[C@@]2(C)CC1 AURFZBICLPNKBZ-FZCSVUEKSA-N 0.000 title claims abstract description 54
- AURFZBICLPNKBZ-UHFFFAOYSA-N Pregnanolone Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(=O)C)C1(C)CC2 AURFZBICLPNKBZ-UHFFFAOYSA-N 0.000 title abstract description 38
- 150000003431 steroids Chemical class 0.000 claims abstract description 41
- 208000015114 central nervous system disease Diseases 0.000 claims abstract description 15
- 238000004519 manufacturing process Methods 0.000 claims abstract description 15
- 208000019022 Mood disease Diseases 0.000 claims abstract description 10
- 230000000694 effects Effects 0.000 claims description 55
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- 208000016255 tiredness Diseases 0.000 claims description 20
- 230000002265 prevention Effects 0.000 claims description 16
- 210000003169 central nervous system Anatomy 0.000 claims description 15
- 206010002091 Anaesthesia Diseases 0.000 claims description 11
- 230000037005 anaesthesia Effects 0.000 claims description 11
- 206010015037 epilepsy Diseases 0.000 claims description 11
- 206010036618 Premenstrual syndrome Diseases 0.000 claims description 10
- 238000001949 anaesthesia Methods 0.000 claims description 10
- 229940127234 oral contraceptive Drugs 0.000 claims description 9
- 239000003539 oral contraceptive agent Substances 0.000 claims description 9
- 238000002560 therapeutic procedure Methods 0.000 claims description 7
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- 239000000203 mixture Substances 0.000 claims description 6
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- 230000002175 menstrual effect Effects 0.000 claims 2
- 206010052804 Drug tolerance Diseases 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 8
- 208000024891 symptom Diseases 0.000 abstract description 2
- 102000004300 GABA-A Receptors Human genes 0.000 description 20
- 108090000839 GABA-A Receptors Proteins 0.000 description 20
- 230000027455 binding Effects 0.000 description 17
- 239000000126 substance Substances 0.000 description 16
- 230000008859 change Effects 0.000 description 15
- 238000001727 in vivo Methods 0.000 description 11
- AURFZBICLPNKBZ-JJYAXCJVSA-N 3-hydroxy-5alpha-pregnan-20-one Chemical compound C([C@@H]1CC2)C(O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](C(=O)C)[C@@]2(C)CC1 AURFZBICLPNKBZ-JJYAXCJVSA-N 0.000 description 10
- 238000000034 method Methods 0.000 description 10
- 230000003444 anaesthetic effect Effects 0.000 description 9
- 229960002200 flunitrazepam Drugs 0.000 description 9
- 238000001802 infusion Methods 0.000 description 9
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- PPTYJKAXVCCBDU-UHFFFAOYSA-N Rohypnol Chemical compound N=1CC(=O)N(C)C2=CC=C([N+]([O-])=O)C=C2C=1C1=CC=CC=C1F PPTYJKAXVCCBDU-UHFFFAOYSA-N 0.000 description 8
- AURFZBICLPNKBZ-SYBPFIFISA-N brexanolone Chemical compound C([C@@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](C(=O)C)[C@@]2(C)CC1 AURFZBICLPNKBZ-SYBPFIFISA-N 0.000 description 8
- 238000001990 intravenous administration Methods 0.000 description 8
- AURFZBICLPNKBZ-YZRLXODZSA-N 3alpha-hydroxy-5beta-pregnan-20-one Chemical group C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](C(=O)C)[C@@]2(C)CC1 AURFZBICLPNKBZ-YZRLXODZSA-N 0.000 description 7
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 6
- 229950007402 eltanolone Drugs 0.000 description 6
- 230000029849 luteinization Effects 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 5
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- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 5
- 230000035945 sensitivity Effects 0.000 description 5
- CYKYBWRSLLXBOW-GDYGHMJCSA-N 5-alpha-THDOC Chemical compound C1[C@H](O)CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)C(=O)CO)[C@@H]4[C@@H]3CC[C@H]21 CYKYBWRSLLXBOW-GDYGHMJCSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 4
- 229920000858 Cyclodextrin Polymers 0.000 description 4
- 206010012289 Dementia Diseases 0.000 description 4
- 229940124326 anaesthetic agent Drugs 0.000 description 4
- 239000003098 androgen Substances 0.000 description 4
- 239000005557 antagonist Substances 0.000 description 4
- 210000004556 brain Anatomy 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 4
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 4
- AURFZBICLPNKBZ-GRWISUQFSA-N 3beta-hydroxy-5beta-pregnan-20-one Chemical compound C([C@H]1CC2)[C@@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](C(=O)C)[C@@]2(C)CC1 AURFZBICLPNKBZ-GRWISUQFSA-N 0.000 description 3
- VTBHBNXGFPTBJL-UHFFFAOYSA-N 4-tert-butyl-1-sulfanylidene-2,6,7-trioxa-1$l^{5}-phosphabicyclo[2.2.2]octane Chemical compound C1OP2(=S)OCC1(C(C)(C)C)CO2 VTBHBNXGFPTBJL-UHFFFAOYSA-N 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 229940049706 benzodiazepine Drugs 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 230000003828 downregulation Effects 0.000 description 3
- 230000002708 enhancing effect Effects 0.000 description 3
- 230000001506 immunosuppresive effect Effects 0.000 description 3
- 230000005906 menstruation Effects 0.000 description 3
- 230000001537 neural effect Effects 0.000 description 3
- 239000000186 progesterone Substances 0.000 description 3
- 229960003387 progesterone Drugs 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 206010001497 Agitation Diseases 0.000 description 2
- 206010010904 Convulsion Diseases 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 150000001557 benzodiazepines Chemical class 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 230000012173 estrus Effects 0.000 description 2
- 229940035423 ethyl ether Drugs 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 230000000324 neuroprotective effect Effects 0.000 description 2
- 239000002858 neurotransmitter agent Substances 0.000 description 2
- 230000002611 ovarian Effects 0.000 description 2
- 150000003146 progesterones Chemical class 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 239000000932 sedative agent Substances 0.000 description 2
- 230000001624 sedative effect Effects 0.000 description 2
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 description 1
- 239000003148 4 aminobutyric acid receptor blocking agent Substances 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 108090000312 Calcium Channels Proteins 0.000 description 1
- 102000003922 Calcium Channels Human genes 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 102000005915 GABA Receptors Human genes 0.000 description 1
- 108010005551 GABA Receptors Proteins 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 238000012404 In vitro experiment Methods 0.000 description 1
- 208000026139 Memory disease Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 108090000189 Neuropeptides Proteins 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- LHNKBXRFNPMIBR-UHFFFAOYSA-N Picrotoxin Natural products CC(C)(O)C1(O)C2OC(=O)C1C3(O)C4OC4C5C(=O)OC2C35C LHNKBXRFNPMIBR-UHFFFAOYSA-N 0.000 description 1
- 206010036600 Premature labour Diseases 0.000 description 1
- 206010039897 Sedation Diseases 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 230000001270 agonistic effect Effects 0.000 description 1
- 230000003281 allosteric effect Effects 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 230000003556 anti-epileptic effect Effects 0.000 description 1
- 230000002460 anti-migrenic effect Effects 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 230000000949 anxiolytic effect Effects 0.000 description 1
- 229940125717 barbiturate Drugs 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 230000009460 calcium influx Effects 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 239000003245 coal Substances 0.000 description 1
- 230000019771 cognition Effects 0.000 description 1
- 230000008094 contradictory effect Effects 0.000 description 1
- 239000003179 convulsant agent Substances 0.000 description 1
- 210000004246 corpus luteum Anatomy 0.000 description 1
- 230000000881 depressing effect Effects 0.000 description 1
- 230000000994 depressogenic effect Effects 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000013401 experimental design Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000003193 general anesthetic agent Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 230000002766 immunoenhancing effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 239000002555 ionophore Substances 0.000 description 1
- 230000000236 ionophoric effect Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000009245 menopause Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000036651 mood Effects 0.000 description 1
- 230000001722 neurochemical effect Effects 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 230000008587 neuronal excitability Effects 0.000 description 1
- 230000011599 ovarian follicle development Effects 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- VJKUPQSHOVKBCO-AHMKVGDJSA-N picrotoxin Chemical compound O=C([C@@]12O[C@@H]1C[C@]1(O)[C@@]32C)O[C@@H]3[C@H]2[C@@H](C(=C)C)[C@@H]1C(=O)O2.O=C([C@@]12O[C@@H]1C[C@]1(O)[C@@]32C)O[C@@H]3[C@H]2[C@@H](C(C)(O)C)[C@@H]1C(=O)O2 VJKUPQSHOVKBCO-AHMKVGDJSA-N 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 230000003169 placental effect Effects 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- -1 pregnane steroids Chemical class 0.000 description 1
- 150000003128 pregnanes Chemical class 0.000 description 1
- 230000001739 rebound effect Effects 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000028527 righting reflex Effects 0.000 description 1
- 230000036280 sedation Effects 0.000 description 1
- 238000007391 self-medication Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 238000013222 sprague-dawley male rat Methods 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L sulfate group Chemical group S(=O)(=O)([O-])[O-] QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
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- 210000003462 vein Anatomy 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/18—Feminine contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P23/00—Anaesthetics
-
- 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
- A61P25/06—Antimigraine agents
-
- 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
- A61P25/08—Antiepileptics; Anticonvulsants
-
- 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
- A61P25/20—Hypnotics; Sedatives
-
- 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
- A61P25/24—Antidepressants
-
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- 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
- A61P5/00—Drugs for disorders of the endocrine system
Landscapes
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Pain & Pain Management (AREA)
- Endocrinology (AREA)
- Epidemiology (AREA)
- Psychiatry (AREA)
- Reproductive Health (AREA)
- Anesthesiology (AREA)
- Hospice & Palliative Care (AREA)
- Gynecology & Obstetrics (AREA)
- Diabetes (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US3786998A | 1998-03-11 | 1998-03-11 | |
| US09/037,869 | 1998-03-11 | ||
| PCT/EP1999/001496 WO1999045931A1 (en) | 1998-03-11 | 1999-03-10 | Epiallopregnanolone in the treatment of cns disorders |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2321728A1 CA2321728A1 (en) | 1999-09-16 |
| CA2321728C true CA2321728C (en) | 2008-12-09 |
Family
ID=21896803
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002321728A Expired - Fee Related CA2321728C (en) | 1998-03-11 | 1999-03-10 | Epiallopregnanolone in the treatment of cns disorders |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US6455516B1 (enExample) |
| EP (1) | EP1063999B1 (enExample) |
| JP (1) | JP3877961B2 (enExample) |
| CN (1) | CN1270718C (enExample) |
| AT (1) | ATE307592T1 (enExample) |
| AU (1) | AU756001B2 (enExample) |
| CA (1) | CA2321728C (enExample) |
| DE (1) | DE69927960T2 (enExample) |
| WO (1) | WO1999045931A1 (enExample) |
Families Citing this family (34)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20020072509A1 (en) * | 2000-10-11 | 2002-06-13 | Stein Donald Gerald | Methods for the treatment of a traumatic central nervous system injury |
| SE0104423D0 (sv) | 2001-12-27 | 2001-12-27 | Umecrine Ab | Pregnane steroids and their use in the treatment of CNS disorders |
| RU2413516C2 (ru) * | 2004-11-18 | 2011-03-10 | Умекрин Аб | Гамк-стероидные антагонисты и их применение в лечении нарушений цнс |
| JP4914368B2 (ja) * | 2004-11-18 | 2012-04-11 | ウメクライン アーベー | Ｇａｂａ−ステロイド拮抗剤およびｃｎｓ疾患の治療のためのその使用 |
| DE102006003509A1 (de) * | 2006-01-24 | 2007-07-26 | Grünenthal GmbH | Kontrazeptivum |
| DE102006003508A1 (de) * | 2006-01-24 | 2007-07-26 | Grünenthal GmbH | Arzneimittel umfassend eine Hormonkombination |
| US20070203216A1 (en) * | 2006-02-14 | 2007-08-30 | Bjarke Ebert | Method of treating inflammatory diseases |
| PL2711371T3 (pl) | 2006-11-21 | 2018-06-29 | Asarina Pharma Ab | Zastosowanie steroidów pregnanowych i androstanowych do wytwarzania kompozycji farmaceutycznej do leczenia zaburzeń oun |
| WO2008154579A1 (en) * | 2007-06-11 | 2008-12-18 | University Of Southern California | Allopregnanolone in a method for enhancing neurological function (alzheimer disease) |
| US20100204192A1 (en) | 2007-06-11 | 2010-08-12 | University Of Sourthern California | Agents, compositions and methods for enhancing neurological function |
| US20090048288A1 (en) * | 2007-08-13 | 2009-02-19 | H. Lundbeck A/S | Method of treating stress-mediated depression |
| WO2011087441A1 (en) * | 2010-01-14 | 2011-07-21 | Umecrine Mood Ab | A pharmaceutical composition comprising 3-beta-hydroxy-5-alpha-pregnan-20-one with improved storage and solubility properties |
| US10150793B2 (en) * | 2011-05-20 | 2018-12-11 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Antagonists of CB1 receptor |
| WO2013043985A1 (en) | 2011-09-23 | 2013-03-28 | The Regents Of The University Of California | Edible oils to enhance delivery of orally administered steroids |
| DK2806877T3 (da) * | 2012-01-23 | 2019-11-04 | Sage Therapeutics Inc | Neuroaktive steroidformuleringer omfattende et kompleks af allopregnanolon og sulfobutylether beta-cyclodekstrin |
| US20140050789A1 (en) | 2012-08-13 | 2014-02-20 | The Regents Of The University Of California | Mitigation of epileptic seizures by combination therapy using benzodiazepines and neurosteroids |
| CA2882708A1 (en) | 2012-08-21 | 2014-02-27 | Sage Therapeutics, Inc. | Methods of treating epilepsy or status epilepticus |
| HRP20170503T1 (hr) | 2012-11-28 | 2017-06-16 | Institut National De La Santé Et De La Recherche Médicale (Inserm) | 3-(4'-supstituirani)-benzil-eter derivati pregnenolona |
| JP2016501876A (ja) * | 2012-11-30 | 2016-01-21 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | ステロイドの抗痙攣活性 |
| ME03351B (me) | 2014-01-29 | 2019-10-20 | Umecrine Cognition Ab | Steroidno jedinjenje za upotrebu u lečenju hepatične encefalopatije |
| JOP20200195A1 (ar) | 2014-09-08 | 2017-06-16 | Sage Therapeutics Inc | سترويدات وتركيبات نشطة عصبياً، واستخداماتها |
| SMT202000276T1 (it) * | 2014-11-27 | 2020-07-08 | Sage Therapeutics Inc | Composizioni e metodi per trattare disturbi del snc |
| AR103384A1 (es) | 2015-01-12 | 2017-05-03 | Umecrine Cognition Ab | 3a-ETINILO, 3b-HIDROXI, 5a-PREGNAN-20-OXIMA COMO MODULADOR DE GABA |
| WO2017156103A1 (en) | 2016-03-08 | 2017-09-14 | Sage Therapeutics, Inc. | Neuroactive steroids, compositions, and uses thereof |
| US10278977B2 (en) | 2016-06-06 | 2019-05-07 | Umecrine Cognition Ab | Methods for treating hypersomnolence |
| RS67063B1 (sr) | 2017-01-09 | 2025-08-29 | Relmada Therapeutics Inc | Injektabilne suspenzije |
| AU2018218823B2 (en) * | 2017-02-10 | 2022-12-22 | Relmada Therapeutics, Inc. | 3-beta-hydroxy-5-alpha-pregnan-20-one for use in medical treatment |
| WO2018147791A1 (en) | 2017-02-10 | 2018-08-16 | Asarina Pharma Ab | 3-beta-hydroxy-5-alpha-pregnan-20-one for use in treatment of essential tremor |
| US20210228596A1 (en) * | 2017-10-12 | 2021-07-29 | Sage Therapeutics, Inc. | Method of treating cns disorders with neurosteroids and gabaergic compounds |
| RU2020130861A (ru) | 2018-04-05 | 2022-05-05 | Асарина Фарма Апс | Антагонисты гамка для применения в лечении расстройств отмены психоактивного вещества |
| US20240383942A1 (en) | 2021-09-14 | 2024-11-21 | Nanjing Minova Pharmaceutical Co., Ltd. | Water-soluble allopregnanolone derivative, and preparation method therefor and use thereof |
| US20240383941A1 (en) | 2021-11-10 | 2024-11-21 | Umecrine Ab | 3-alpha substituted 3-beta-hydroxy-17-oximated androstane compound for modulation of the alpha-3 subtype of the gabaa receptor |
| WO2023083980A1 (en) | 2021-11-10 | 2023-05-19 | Umecrine Ab | Steroid as a modulator of gabaa receptor |
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| US5232917A (en) * | 1987-08-25 | 1993-08-03 | University Of Southern California | Methods, compositions, and compounds for allosteric modulation of the GABA receptor by members of the androstane and pregnane series |
| US5120723A (en) | 1987-08-25 | 1992-06-09 | University Of Southern California | Method, compositions, and compounds for modulating brain excitability |
| WO1995005826A1 (en) * | 1993-08-20 | 1995-03-02 | Jackson Meyer B | Method for regulating neuropeptide hormone secretion |
| US5939545A (en) * | 1994-02-14 | 1999-08-17 | Cocensys, Inc. | Method, compositions, and compounds for allosteric modulation of the gaba receptor by members of the androstane and pregnane series |
| CA2205919A1 (en) * | 1994-11-23 | 1996-05-30 | Cocensys, Inc. | Androstane and pregnane series for allosteric modulation of gaba receptor |
| DK0981349T3 (da) * | 1997-05-02 | 2003-03-10 | Wyeth Corp | 5-alfa-pregnan-3-beta-ol-20-on-sulfat til behandling af tumorer og CNS sygdomme |
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1999
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- 1999-03-10 AU AU33292/99A patent/AU756001B2/en not_active Ceased
- 1999-03-10 JP JP2000535346A patent/JP3877961B2/ja not_active Expired - Fee Related
- 1999-03-10 EP EP99914491A patent/EP1063999B1/en not_active Expired - Lifetime
- 1999-03-10 CA CA002321728A patent/CA2321728C/en not_active Expired - Fee Related
- 1999-03-10 CN CNB998060283A patent/CN1270718C/zh not_active Expired - Fee Related
- 1999-03-10 DE DE69927960T patent/DE69927960T2/de not_active Expired - Lifetime
- 1999-03-10 WO PCT/EP1999/001496 patent/WO1999045931A1/en not_active Ceased
- 1999-03-11 US US09/266,035 patent/US6455516B1/en not_active Expired - Lifetime
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| CA2321728A1 (en) | 1999-09-16 |
| US6455516B1 (en) | 2002-09-24 |
| JP2002506034A (ja) | 2002-02-26 |
| DE69927960D1 (de) | 2005-12-01 |
| WO1999045931A1 (en) | 1999-09-16 |
| AU756001B2 (en) | 2003-01-02 |
| EP1063999B1 (en) | 2005-10-26 |
| AU3329299A (en) | 1999-09-27 |
| CN1270718C (zh) | 2006-08-23 |
| DE69927960T2 (de) | 2006-07-20 |
| EP1063999A1 (en) | 2001-01-03 |
| CN1300219A (zh) | 2001-06-20 |
| ATE307592T1 (de) | 2005-11-15 |
| JP3877961B2 (ja) | 2007-02-07 |
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