CA3024081A1 - Procedes de traitement de la dependance aux opioides et des symptomes de sevrage en utilisant de la noribogaine - Google Patents
Procedes de traitement de la dependance aux opioides et des symptomes de sevrage en utilisant de la noribogaine Download PDFInfo
- Publication number
- CA3024081A1 CA3024081A1 CA3024081A CA3024081A CA3024081A1 CA 3024081 A1 CA3024081 A1 CA 3024081A1 CA 3024081 A CA3024081 A CA 3024081A CA 3024081 A CA3024081 A CA 3024081A CA 3024081 A1 CA3024081 A1 CA 3024081A1
- Authority
- CA
- Canada
- Prior art keywords
- noribogaine
- opioid
- patient
- substituted
- derivative
- 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.)
- Abandoned
Links
- RAUCDOKTMDOIPF-RYRUWHOVSA-N noribogaine Chemical compound N1([C@@H]2[C@H]3C[C@H](C1)C[C@@H]2CC)CCC1=C3NC2=CC=C(O)C=C12 RAUCDOKTMDOIPF-RYRUWHOVSA-N 0.000 title claims abstract description 554
- RAUCDOKTMDOIPF-UHFFFAOYSA-N hydroxyibogamine Natural products CCC1CC(C2)CC3C1N2CCC1=C3NC2=CC=C(O)C=C12 RAUCDOKTMDOIPF-UHFFFAOYSA-N 0.000 title claims abstract description 330
- 238000000034 method Methods 0.000 title claims abstract description 125
- 238000011282 treatment Methods 0.000 title claims description 138
- 150000003839 salts Chemical class 0.000 claims abstract description 133
- 239000012453 solvate Substances 0.000 claims abstract description 129
- 239000003401 opiate antagonist Substances 0.000 claims abstract description 125
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 claims abstract description 60
- 230000001419 dependent effect Effects 0.000 claims abstract description 46
- 229940124636 opioid drug Drugs 0.000 claims abstract description 17
- 230000001154 acute effect Effects 0.000 claims abstract description 16
- 230000001225 therapeutic effect Effects 0.000 claims description 53
- 239000000203 mixture Substances 0.000 claims description 44
- UZHSEJADLWPNLE-GRGSLBFTSA-N naloxone Chemical compound O=C([C@@H]1O2)CC[C@@]3(O)[C@H]4CC5=CC=C(O)C2=C5[C@@]13CCN4CC=C UZHSEJADLWPNLE-GRGSLBFTSA-N 0.000 claims description 35
- 229960004127 naloxone Drugs 0.000 claims description 35
- 210000002966 serum Anatomy 0.000 claims description 35
- 238000012423 maintenance Methods 0.000 claims description 32
- 230000004060 metabolic process Effects 0.000 claims description 29
- 229960003086 naltrexone Drugs 0.000 claims description 25
- DQCKKXVULJGBQN-XFWGSAIBSA-N naltrexone Chemical compound N1([C@@H]2CC3=CC=C(C=4O[C@@H]5[C@](C3=4)([C@]2(CCC5=O)O)CC1)O)CC1CC1 DQCKKXVULJGBQN-XFWGSAIBSA-N 0.000 claims description 25
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- 238000009472 formulation Methods 0.000 claims description 22
- 239000005557 antagonist Substances 0.000 claims description 21
- 230000001965 increasing effect Effects 0.000 claims description 21
- 229940005483 opioid analgesics Drugs 0.000 claims description 21
- UIQMVEYFGZJHCZ-SSTWWWIQSA-N Nalorphine Chemical compound C([C@@H](N(CC1)CC=C)[C@@H]2C=C[C@@H]3O)C4=CC=C(O)C5=C4[C@@]21[C@H]3O5 UIQMVEYFGZJHCZ-SSTWWWIQSA-N 0.000 claims description 18
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- 229940127240 opiate Drugs 0.000 claims description 18
- OZYUPQUCAUTOBP-QXAKKESOSA-N Levallorphan Chemical compound C([C@H]12)CCC[C@@]11CCN(CC=C)[C@@H]2CC2=CC=C(O)C=C21 OZYUPQUCAUTOBP-QXAKKESOSA-N 0.000 claims description 17
- WJBLNOPPDWQMCH-MBPVOVBZSA-N Nalmefene Chemical compound N1([C@@H]2CC3=CC=C(C=4O[C@@H]5[C@](C3=4)([C@]2(CCC5=C)O)CC1)O)CC1CC1 WJBLNOPPDWQMCH-MBPVOVBZSA-N 0.000 claims description 17
- APSUXPSYBJVPPS-YAUKWVCOSA-N Norbinaltorphimine Chemical compound N1([C@@H]2CC3=CC=C(C=4O[C@@H]5[C@](C3=4)([C@]2(CC=2C=3C[C@]4(O)[C@]67CCN(CC8CC8)[C@@H]4CC=4C7=C(C(=CC=4)O)O[C@H]6C=3NC=25)O)CC1)O)CC1CC1 APSUXPSYBJVPPS-YAUKWVCOSA-N 0.000 claims description 17
- INUCRGMCKDQKNA-CEMLEFRQSA-N cyprodime Chemical compound N1([C@@H]2CC=3C=CC=C(C=3[C@@]3([C@]2(CCC(=O)C3)OC)CC1)OC)CC1CC1 INUCRGMCKDQKNA-CEMLEFRQSA-N 0.000 claims description 17
- 229960000263 levallorphan Drugs 0.000 claims description 17
- 229960005297 nalmefene Drugs 0.000 claims description 17
- DKJCUVXSBOMWAV-PCWWUVHHSA-N naltrindole Chemical compound N1([C@H]2CC3=CC=C(C=4O[C@@H]5[C@](C3=4)([C@]2(CC2=C3[CH]C=CC=C3N=C25)O)CC1)O)CC1CC1 DKJCUVXSBOMWAV-PCWWUVHHSA-N 0.000 claims description 17
- 238000012544 monitoring process Methods 0.000 claims description 16
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- 208000024891 symptom Diseases 0.000 claims description 16
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- USSIQXCVUWKGNF-UHFFFAOYSA-N 6-(dimethylamino)-4,4-diphenylheptan-3-one Chemical compound C=1C=CC=CC=1C(CC(C)N(C)C)(C(=O)CC)C1=CC=CC=C1 USSIQXCVUWKGNF-UHFFFAOYSA-N 0.000 claims description 9
- 206010013654 Drug abuse Diseases 0.000 claims description 9
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- 238000002347 injection Methods 0.000 claims description 3
- 239000007924 injection Substances 0.000 claims description 3
- 238000010255 intramuscular injection Methods 0.000 claims description 3
- 239000007927 intramuscular injection Substances 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 238000009535 clinical urine test Methods 0.000 claims description 2
- 230000002401 inhibitory effect Effects 0.000 claims description 2
- RMRJXGBAOAMLHD-IHFGGWKQSA-N buprenorphine Chemical compound C([C@]12[C@H]3OC=4C(O)=CC=C(C2=4)C[C@@H]2[C@]11CC[C@]3([C@H](C1)[C@](C)(O)C(C)(C)C)OC)CN2CC1CC1 RMRJXGBAOAMLHD-IHFGGWKQSA-N 0.000 claims 2
- 125000000623 heterocyclic group Chemical group 0.000 description 122
- 125000001072 heteroaryl group Chemical group 0.000 description 106
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- -1 acetylenyl Chemical group 0.000 description 69
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- 239000001257 hydrogen Substances 0.000 description 63
- 125000000753 cycloalkyl group Chemical group 0.000 description 45
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- 125000003342 alkenyl group Chemical group 0.000 description 40
- 125000000547 substituted alkyl group Chemical group 0.000 description 40
- 229940079593 drug Drugs 0.000 description 39
- 125000005346 substituted cycloalkyl group Chemical group 0.000 description 38
- 125000005017 substituted alkenyl group Chemical group 0.000 description 37
- 125000004426 substituted alkynyl group Chemical group 0.000 description 37
- 150000002431 hydrogen Chemical class 0.000 description 35
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 31
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 22
- 125000004432 carbon atom Chemical group C* 0.000 description 20
- 230000000694 effects Effects 0.000 description 20
- 125000005843 halogen group Chemical group 0.000 description 19
- 238000012216 screening Methods 0.000 description 19
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 18
- 229910052757 nitrogen Inorganic materials 0.000 description 17
- 125000003545 alkoxy group Chemical group 0.000 description 16
- 125000001424 substituent group Chemical group 0.000 description 16
- 150000001875 compounds Chemical class 0.000 description 15
- 230000036470 plasma concentration Effects 0.000 description 15
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 15
- 125000004414 alkyl thio group Chemical group 0.000 description 14
- 125000004104 aryloxy group Chemical group 0.000 description 14
- 125000005842 heteroatom Chemical group 0.000 description 14
- 125000005110 aryl thio group Chemical group 0.000 description 12
- 125000004465 cycloalkenyloxy group Chemical group 0.000 description 12
- 125000005366 cycloalkylthio group Chemical group 0.000 description 12
- 125000005553 heteroaryloxy group Chemical group 0.000 description 12
- 125000005368 heteroarylthio group Chemical group 0.000 description 12
- 125000005844 heterocyclyloxy group Chemical group 0.000 description 12
- 125000004468 heterocyclylthio group Chemical group 0.000 description 12
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 11
- 229960005181 morphine Drugs 0.000 description 11
- 239000000651 prodrug Substances 0.000 description 11
- 229940002612 prodrug Drugs 0.000 description 11
- 125000004093 cyano group Chemical group *C#N 0.000 description 10
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 10
- HSIBGVUMFOSJPD-CFDPKNGZSA-N ibogaine Chemical compound N1([C@@H]2[C@H]3C[C@H](C1)C[C@@H]2CC)CCC1=C3NC2=CC=C(OC)C=C12 HSIBGVUMFOSJPD-CFDPKNGZSA-N 0.000 description 10
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 10
- VOXIUXZAOFEFBL-UHFFFAOYSA-N Voacangin Natural products CCC1CC2CN3CC1C(C2)(OC(=O)C)c4[nH]c5ccc(OC)cc5c4C3 VOXIUXZAOFEFBL-UHFFFAOYSA-N 0.000 description 9
- RMRJXGBAOAMLHD-CTAPUXPBSA-N buprenorphine Chemical compound C([C@]12[C@H]3OC=4C(O)=CC=C(C2=4)C[C@@H]2[C@]11CC[C@@]3([C@H](C1)[C@](C)(O)C(C)(C)C)OC)CN2CC1CC1 RMRJXGBAOAMLHD-CTAPUXPBSA-N 0.000 description 9
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 9
- 235000019788 craving Nutrition 0.000 description 9
- 150000002148 esters Chemical class 0.000 description 9
- OLOCMRXSJQJJPL-UHFFFAOYSA-N ibogaine Natural products CCC1CC2CC3C1N(C2)C=Cc4c3[nH]c5ccc(OC)cc45 OLOCMRXSJQJJPL-UHFFFAOYSA-N 0.000 description 9
- AREITJMUSRHSBK-UHFFFAOYSA-N ibogamine Natural products CCC1CC2C3CC1CN2CCc4c3[nH]c5ccccc45 AREITJMUSRHSBK-UHFFFAOYSA-N 0.000 description 9
- 230000002035 prolonged effect Effects 0.000 description 9
- 108090000790 Enzymes Proteins 0.000 description 8
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- 208000026251 Opioid-Related disease Diseases 0.000 description 8
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- OROGSEYTTFOCAN-DNJOTXNNSA-N codeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC OROGSEYTTFOCAN-DNJOTXNNSA-N 0.000 description 8
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- OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
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- GVGLGOZIDCSQPN-PVHGPHFFSA-N Heroin Chemical compound O([C@H]1[C@H](C=C[C@H]23)OC(C)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4OC(C)=O GVGLGOZIDCSQPN-PVHGPHFFSA-N 0.000 description 6
- BRUQQQPBMZOVGD-XFKAJCMBSA-N Oxycodone Chemical compound O=C([C@@H]1O2)CC[C@@]3(O)[C@H]4CC5=CC=C(OC)C2=C5[C@@]13CCN4C BRUQQQPBMZOVGD-XFKAJCMBSA-N 0.000 description 6
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Classifications
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- 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
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
-
- 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
- A61K31/47—Quinolines; Isoquinolines
- A61K31/485—Morphinan derivatives, e.g. morphine, codeine
-
- 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
- A61K31/66—Phosphorus compounds
- A61K31/661—Phosphorus acids or esters thereof not having P—C bonds, e.g. fosfosal, dichlorvos, malathion or mevinphos
- A61K31/6615—Compounds having two or more esterified phosphorus acid groups, e.g. inositol triphosphate, phytic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/36—Opioid-abuse
Landscapes
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (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)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Addiction (AREA)
- Biomedical Technology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Psychiatry (AREA)
- Emergency Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
La présente invention concerne un procédé de traitement de la dépendance à un médicament opioïde, y compris les symptômes de sevrage aigus et post-aigus, consistant à traiter un patient dépendant aux substances opioïdes avec de la noribogaïne, un dérivé de la noribogaïne, ou un sel ou solvate de la noribogaïne pharmaceutiquement acceptable selon un schéma à doses multiples et éventuellement un antagoniste des récepteurs opioïdes.
Applications Claiming Priority (11)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562159905P | 2015-05-11 | 2015-05-11 | |
| US62/159,905 | 2015-05-11 | ||
| US201562165853P | 2015-05-22 | 2015-05-22 | |
| US62/165,853 | 2015-05-22 | ||
| US201562180579P | 2015-06-16 | 2015-06-16 | |
| US62/180,579 | 2015-06-16 | ||
| US201562247130P | 2015-10-27 | 2015-10-27 | |
| US62/247,130 | 2015-10-27 | ||
| US201562260182P | 2015-11-25 | 2015-11-25 | |
| US62/260,182 | 2015-11-25 | ||
| PCT/US2016/031932 WO2016183244A1 (fr) | 2015-05-11 | 2016-05-11 | Procédés de traitement de la dépendance aux opioïdes et des symptômes de sevrage en utilisant de la noribogaïne |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA3024081A1 true CA3024081A1 (fr) | 2016-11-17 |
Family
ID=57248533
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA3024081A Abandoned CA3024081A1 (fr) | 2015-05-11 | 2016-05-11 | Procedes de traitement de la dependance aux opioides et des symptomes de sevrage en utilisant de la noribogaine |
Country Status (3)
| Country | Link |
|---|---|
| EP (1) | EP3340984A4 (fr) |
| CA (1) | CA3024081A1 (fr) |
| WO (1) | WO2016183244A1 (fr) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11977085B1 (en) | 2023-09-05 | 2024-05-07 | Elan Ehrlich | Date rape drug detection device and method of using same |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2224430T3 (es) * | 1997-09-04 | 2005-03-01 | Novoneuron Inc | Noribogaina en el tratamiento del dolor y de la toxicomania. |
| EP2605813B1 (fr) * | 2010-08-17 | 2018-08-01 | University of Florida Research Foundation, Inc. | Système intelligent d'administration de médicament, destiné à optimiser un traitement médical ou une thérapie. |
| US10702485B2 (en) * | 2011-07-09 | 2020-07-07 | Syntrix Biosystems Inc. | Compositions and methods for overcoming resistance to tramadol |
| CA2942638A1 (fr) * | 2013-03-15 | 2014-09-18 | Demerx, Inc. | Procede pour le traitement avec la noribogaine de l'addiction de patients sous methadone |
-
2016
- 2016-05-11 EP EP16793477.7A patent/EP3340984A4/fr not_active Withdrawn
- 2016-05-11 WO PCT/US2016/031932 patent/WO2016183244A1/fr not_active Ceased
- 2016-05-11 CA CA3024081A patent/CA3024081A1/fr not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| WO2016183244A1 (fr) | 2016-11-17 |
| EP3340984A1 (fr) | 2018-07-04 |
| EP3340984A4 (fr) | 2019-06-19 |
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Legal Events
| Date | Code | Title | Description |
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| EEER | Examination request |
Effective date: 20210505 |
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| EEER | Examination request |
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| EEER | Examination request |
Effective date: 20210505 |
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| EEER | Examination request |
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| EEER | Examination request |
Effective date: 20210505 |
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| FZDE | Discontinued |
Effective date: 20231107 |