WO1998046225A1 - Traitement contre la schizophrenie - Google Patents
Traitement contre la schizophrenie Download PDFInfo
- Publication number
- WO1998046225A1 WO1998046225A1 PCT/US1998/007152 US9807152W WO9846225A1 WO 1998046225 A1 WO1998046225 A1 WO 1998046225A1 US 9807152 W US9807152 W US 9807152W WO 9846225 A1 WO9846225 A1 WO 9846225A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- disorder
- schizophrenia
- chronic
- unspecified
- subchronic
- Prior art date
Links
- 201000000980 schizophrenia Diseases 0.000 title claims abstract description 98
- 238000000034 method Methods 0.000 title claims abstract description 24
- 208000028017 Psychotic disease Diseases 0.000 claims abstract description 38
- 150000001875 compounds Chemical class 0.000 claims abstract description 34
- 208000020186 Schizophreniform disease Diseases 0.000 claims abstract description 7
- 208000022610 schizoaffective disease Diseases 0.000 claims abstract description 7
- 230000009798 acute exacerbation Effects 0.000 claims description 30
- 230000001684 chronic effect Effects 0.000 claims description 30
- JTJMJGYZQZDUJJ-UHFFFAOYSA-N phencyclidine Chemical compound C1CCCCN1C1(C=2C=CC=CC=2)CCCCC1 JTJMJGYZQZDUJJ-UHFFFAOYSA-N 0.000 claims description 30
- 208000024254 Delusional disease Diseases 0.000 claims description 21
- 208000002851 paranoid schizophrenia Diseases 0.000 claims description 21
- 208000022821 personality disease Diseases 0.000 claims description 21
- 239000000126 substance Substances 0.000 claims description 21
- 206010007776 catatonia Diseases 0.000 claims description 18
- 206010012218 Delirium Diseases 0.000 claims description 16
- 229950010883 phencyclidine Drugs 0.000 claims description 15
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 claims description 12
- 239000000380 hallucinogen Substances 0.000 claims description 12
- KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 claims description 9
- 206010012289 Dementia Diseases 0.000 claims description 9
- 208000019022 Mood disease Diseases 0.000 claims description 9
- 239000000150 Sympathomimetic Substances 0.000 claims description 9
- 229940025084 amphetamine Drugs 0.000 claims description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 9
- 230000001575 pathological effect Effects 0.000 claims description 9
- 230000001975 sympathomimetic effect Effects 0.000 claims description 9
- 208000016686 tic disease Diseases 0.000 claims description 9
- 208000027626 Neurocognitive disease Diseases 0.000 claims description 8
- 208000027520 Somatoform disease Diseases 0.000 claims description 8
- 208000035475 disorder Diseases 0.000 claims description 8
- 208000019901 Anxiety disease Diseases 0.000 claims description 6
- 208000027691 Conduct disease Diseases 0.000 claims description 6
- 208000026331 Disruptive, Impulse Control, and Conduct disease Diseases 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- 201000001916 Hypochondriasis Diseases 0.000 claims description 6
- 229960003920 cocaine Drugs 0.000 claims description 6
- 231100000566 intoxication Toxicity 0.000 claims description 6
- 230000035987 intoxication Effects 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 6
- 239000012453 solvate Substances 0.000 claims description 4
- 208000007848 Alcoholism Diseases 0.000 claims description 3
- 206010002859 Anxiety disorder due to a general medical condition Diseases 0.000 claims description 3
- 241000218236 Cannabis Species 0.000 claims description 3
- 208000017781 Cocaine intoxication Diseases 0.000 claims description 3
- 206010012225 Delirium tremens Diseases 0.000 claims description 3
- 208000001613 Gambling Diseases 0.000 claims description 3
- 208000011688 Generalised anxiety disease Diseases 0.000 claims description 3
- 208000030990 Impulse-control disease Diseases 0.000 claims description 3
- 206010027944 Mood disorder due to a general medical condition Diseases 0.000 claims description 3
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 claims description 3
- 231100000643 Substance intoxication Toxicity 0.000 claims description 3
- 208000023655 Tic Diseases 0.000 claims description 3
- 208000000323 Tourette Syndrome Diseases 0.000 claims description 3
- 208000016620 Tourette disease Diseases 0.000 claims description 3
- 201000007930 alcohol dependence Diseases 0.000 claims description 3
- 208000006246 alcohol withdrawal delirium Diseases 0.000 claims description 3
- 208000022266 body dysmorphic disease Diseases 0.000 claims description 3
- 208000021703 chronic tic disease Diseases 0.000 claims description 3
- 208000029364 generalized anxiety disease Diseases 0.000 claims description 3
- 208000015046 intermittent explosive disease Diseases 0.000 claims description 3
- 206010023461 kleptomania Diseases 0.000 claims description 3
- 230000008447 perception Effects 0.000 claims description 3
- 208000028173 post-traumatic stress disease Diseases 0.000 claims description 3
- 208000027100 transient tic disease Diseases 0.000 claims description 3
- 208000002271 trichotillomania Diseases 0.000 claims description 3
- 208000001836 Firesetting Behavior Diseases 0.000 claims description 2
- 206010034158 Pathological gambling Diseases 0.000 claims description 2
- 208000033039 Somatisation disease Diseases 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 201000004645 pyromania Diseases 0.000 claims description 2
- 208000016994 somatization disease Diseases 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 230000004044 response Effects 0.000 description 12
- 230000001143 conditioned effect Effects 0.000 description 7
- 230000035939 shock Effects 0.000 description 7
- 238000011282 treatment Methods 0.000 description 7
- 241001465754 Metazoa Species 0.000 description 6
- 230000000694 effects Effects 0.000 description 5
- 230000000561 anti-psychotic effect Effects 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 239000000164 antipsychotic agent Substances 0.000 description 3
- 241000700159 Rattus Species 0.000 description 2
- 230000006735 deficit Effects 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 230000003340 mental effect Effects 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 239000000902 placebo Substances 0.000 description 2
- 229940068196 placebo Drugs 0.000 description 2
- 230000036515 potency Effects 0.000 description 2
- 208000020016 psychiatric disease Diseases 0.000 description 2
- SBCXBWBXWKVIFK-PBBCPHEYSA-N (e)-but-2-enedioic acid;(3r)-3-prop-2-ynoxy-1-azabicyclo[2.2.2]octane Chemical compound OC(=O)\C=C\C(O)=O.C1CC2[C@@H](OCC#C)CN1CC2 SBCXBWBXWKVIFK-PBBCPHEYSA-N 0.000 description 1
- 206010001497 Agitation Diseases 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 241001233887 Ania Species 0.000 description 1
- XVFJONKUSLSKSW-JTQLQIEISA-N C#CCO[C@@H]1C(CC2)CCN2C1 Chemical compound C#CCO[C@@H]1C(CC2)CCN2C1 XVFJONKUSLSKSW-JTQLQIEISA-N 0.000 description 1
- 241000557626 Corvus corax Species 0.000 description 1
- 206010012239 Delusion Diseases 0.000 description 1
- 102000015554 Dopamine receptor Human genes 0.000 description 1
- 108050004812 Dopamine receptor Proteins 0.000 description 1
- 208000004547 Hallucinations Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 206010027951 Mood swings Diseases 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 206010041243 Social avoidant behaviour Diseases 0.000 description 1
- 206010044565 Tremor Diseases 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- VMWNQDUVQKEIOC-CYBMUJFWSA-N apomorphine Chemical compound C([C@H]1N(C)CC2)C3=CC=C(O)C(O)=C3C3=C1C2=CC=C3 VMWNQDUVQKEIOC-CYBMUJFWSA-N 0.000 description 1
- 229960004046 apomorphine Drugs 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 238000009227 behaviour therapy Methods 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 230000009194 climbing Effects 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 231100000868 delusion Toxicity 0.000 description 1
- 230000009699 differential effect Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000003176 neuroleptic agent Substances 0.000 description 1
- 230000000701 neuroleptic effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 239000004089 psychotropic agent Substances 0.000 description 1
- WQGWDDDVZFFDIG-UHFFFAOYSA-N pyrogallol Chemical compound OC1=CC=CC(O)=C1O WQGWDDDVZFFDIG-UHFFFAOYSA-N 0.000 description 1
- -1 quinuclidine compound Chemical class 0.000 description 1
- 238000007920 subcutaneous administration Methods 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
- A61K31/435—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
- A61K31/439—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 the ring forming part of a bridged ring system, e.g. quinuclidine
Definitions
- This invention provides a method for treating or alleviating the symptoms of pathologic psychosis, comprising administering an effective amount of a cyano-oxime compound.
- the method of this invention provides a method for treating schizophrenia using compounds which were previously disclosed for use in the treatment of Alzheimer's Disease.
- the method of this invention provide the clinician with another treatment option for the treatment of psychotic conditions.
- the compounds used in the presently claimed method appear to have an acceptable side effect profile while providing surprising anti-psychotic activity.
- the present invention provides a method for treating a condition selected from the group consisting of schizophrenia, schizophreniform disorder, and schizoaffective disorder, comprising administering an effective amount of Compound I:
- the present invention provides a method for treating a pathologic psychotic condition selected from the group consisting of Conduct Disorder, Solitary Aggressive Type (312.00), Conduct Disorder, Undifferentiated Type (312.90), Tourette's Disorder (307.23), Chronic Motor Or Vocal Tic Disorder (307.22), Transient Tic Disorder (307.21), Tic Disorder NOS (307.20), Alcohol Withdrawal Delirium (291.00), Alcohol Hallucinosis (291.30), Alcohol Dementia Associated with Alcoholism (291.20), Amphetamine or Similarly Acting Sympathomimetic Intoxication (305.70), Amphetamine or Similarly Acting Sympathomimetic Delirium (292.81), Amphetamine or Similarly Acting Sympathomimetic Delusional Disorder (292.11), Cannabis Delusional Disorder (292.11), Cocaine Intoxication (305.60), Cocaine Delirium (292.81), Cocaine Delusional Disorder (292.11), Hallucinogen Hallucinosis (305.30), Hallucin
- Post-traumatic Stress Disorder (309.89), Generalized Anxiety Disorder (300.02), Anxiety Disorder NOS (300.00), Body Dysmorphic Disorder (300.70), Hypochondriasis (or Hypochondriacal Neurosis) (300.70), Somatization Disorder (300.81), Undifferentiated Somatoform Disorder (300.70), Somatoform Disorder NOS (300.70), Intermittent Explosive Disorder (312.34), Kleptomania (312.32), Pathological
- Schizophrenia Catatonic, Chronic with Acute Exacerbation (295.24), Schizophrenia, Catatonic, in Remission (295.55), Schizophrenia, Catatonic, Unspecified (295.20), Schizophrenia, Disorganized, Subchronic (295.11), Schizophrenia, Disorganized, Chronic (295.12),
- a particularly preferred Compound I is of the formula II:
- the compound may further be delivered by a variety of other pharmaceutically accepted routes including, but in no way limited to parenterally, subcutaneous, intranasal, intramuscular and intravenous routes.
- Such formulations may be designed to provide delayed or controlled release using formulation techniques which are known in the art.
- Arylcyclohexylamine Organic Mental Disorder NOS (292.90), Other or Unspecified Psychoactive Substance Intoxication (305.90), Other or Unspecified Psychoactive Substance Delirium (292.81), Other or Unspecified Psychoactive Substance Dementia (292.82), Other or Unspecified Psychoactive Substance Delusional Disorder (292.11), Other or Unspecified Psychoactive SubstanHallucinosis (292.12), Other or Unspecified Psychoactive Substance Mood Disorder (292.84), Other or Unspecified Psychoactive Substance Anxiety Disorder (292.89), Other or Unspecified Psychoactive Substance Personality Disorder (292.89), Other or Unspecified Psychoactive Substance Organic
- Obsessive Compulsive Disorder (300.30), Post-traumatic Stress Disorder (309.89), Generalized Anxiety Disorder (300.02), Anxiety Disorder NOS (300.00), Body Dysmorphic Disorder (300.70), Hypochondriasis (or Hypochondriacal Neurosis) (300.70), So atization Disorder (300.81),
- This activity can be demonstrated in models using well-established procedures.
- the compound is assessed in a number of standard behavioral tests predictive of antipsychotic activity.
- Antagonism of apomorphine-induced climbing in mice is predictive of antipsychotic activity (see, Moore, N.A. et al. Psychopharmacology 9 ⁇ (2), 263-266 (1988), and 96_ 539 (1988) ) .
- the conditioned avoidance model as described by Davidson, A.B. Differential Effect of Neuroleptic and other Psychotropic Agents on Acquisition of Avoidance in Rats, Life Sci . 1_8: 1279-1284 (1976) .
- conditioned avoidance test animals learn to respond during a conditioned stimulus in order to avoid mild shock presentation.
- a response during the conditioned stimulus is termed an avoidance response
- a response during shock is termed an escape response
- a response failure is when the animal fails to respond either during the conditioned stimulus or the shock presentation and is indicative of motor impairment.
- Animals rapidly learn to avoid 99% of the time.
- Antipsychotic drugs decrease the percentage of avoidance without interfering with the ability of the animal to respond since the animals do emit escape responses. The percentage of response failures is considered a measure of motor impairment. Procedure .
- Example 1 Human Clinical Trials The activity of Compound I for treating or alleviating psychosis can be demonstrated by human clinical trials.
- the study was designed as a double-blind, parallel, placebo-controlled multicenter trial. The patients are randomized into four groups, placebo and 3 other dosages of test compound. The dosages are administered orally with food. Patients are observed at four visits to provide baseline measurements. Visits 5-33 served as the treatment phase for the study.
- Treatment groups are compared with respect to the number and percent of patients who ever had the symptom during the double-blind portion of the study (visits 5 through 33) , at a severity that was worse than during the baseline visits (1 through 4) .
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
La présente invention concerne un traitement permettant de soigner un patient souffrant d'un état appartenant au groupe constitué de la schizophrénie, du trouble schizo-affectif et du trouble schizophréniforme. Ce traitement utilise pour le patient considéré un composé représenté par la formule (I).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU68960/98A AU6896098A (en) | 1997-04-11 | 1998-04-08 | Method for treating schizophrenia |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US4357097P | 1997-04-11 | 1997-04-11 | |
| US60/043,570 | 1997-04-11 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1998046225A1 true WO1998046225A1 (fr) | 1998-10-22 |
Family
ID=21927829
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US1998/007152 WO1998046225A1 (fr) | 1997-04-11 | 1998-04-08 | Traitement contre la schizophrenie |
Country Status (2)
| Country | Link |
|---|---|
| AU (1) | AU6896098A (fr) |
| WO (1) | WO1998046225A1 (fr) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002064124A2 (fr) * | 2001-02-15 | 2002-08-22 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Composition medicamenteuse qui contient un agoniste muscarinique |
| US10154988B2 (en) | 2012-11-14 | 2018-12-18 | The Johns Hopkins University | Methods and compositions for treating schizophrenia |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5451587A (en) * | 1988-11-22 | 1995-09-19 | Boehringer Ingelheim Gmbh | Quinuclidines, their use as medicaments and processes for their preparation |
-
1998
- 1998-04-08 AU AU68960/98A patent/AU6896098A/en not_active Abandoned
- 1998-04-08 WO PCT/US1998/007152 patent/WO1998046225A1/fr active Application Filing
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5451587A (en) * | 1988-11-22 | 1995-09-19 | Boehringer Ingelheim Gmbh | Quinuclidines, their use as medicaments and processes for their preparation |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002064124A2 (fr) * | 2001-02-15 | 2002-08-22 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Composition medicamenteuse qui contient un agoniste muscarinique |
| WO2002064124A3 (fr) * | 2001-02-15 | 2002-12-05 | Boehringer Ingelheim Pharma | Composition medicamenteuse qui contient un agoniste muscarinique |
| US10154988B2 (en) | 2012-11-14 | 2018-12-18 | The Johns Hopkins University | Methods and compositions for treating schizophrenia |
| EP3610890A1 (fr) | 2012-11-14 | 2020-02-19 | The Johns Hopkins University | Procédés et compositions de traitement de la schizophrénie |
| US10624875B2 (en) | 2012-11-14 | 2020-04-21 | The Johns Hopkins University | Methods and compositions for treating schizophrenia |
Also Published As
| Publication number | Publication date |
|---|---|
| AU6896098A (en) | 1998-11-11 |
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