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WO1998046225A1 - Traitement contre la schizophrenie - Google Patents

Traitement contre la schizophrenie Download PDF

Info

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
Application number
PCT/US1998/007152
Other languages
English (en)
Inventor
Harlan Edgar Shannon
Celia Ann Whitesitt
Original Assignee
Eli Lilly And Company
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Eli Lilly And Company filed Critical Eli Lilly And Company
Priority to AU68960/98A priority Critical patent/AU6896098A/en
Publication of WO1998046225A1 publication Critical patent/WO1998046225A1/fr

Links

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).
PCT/US1998/007152 1997-04-11 1998-04-08 Traitement contre la schizophrenie WO1998046225A1 (fr)

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)

* Cited by examiner, † Cited by third party
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)

* Cited by examiner, † Cited by third party
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

Patent Citations (1)

* Cited by examiner, † Cited by third party
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)

* Cited by examiner, † Cited by third party
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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