Combination of a glycine transporter (GLYT1) inhibitor and an antipsychotic for the treatment of symptoms of schizophrenia as well as its preparation and use thereof

• US 20060154919A1
• Filed: 12/15/2005
• Published: 07/13/2006
• Est. Priority Date: 12/16/2004
• Status: Abandoned Application

• Current Assignee: Janssen Pharmaceutica NV (Johnson & Johnson)
• Original Assignee: Janssen Pharmaceutica NV (Johnson & Johnson)
• Inventors: Moyer, John Allen, Ashton, David, Kalivas, Peter, Klitenick, Mark
• Application Number:
  US11/304,175
• Publication Number:
  US 20060154919A1
• Time in Patent Office: Days
• US Class Current: 514/220
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/34 having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
• CPC Class Codes: A61K 31/341 not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine
• CPC Class Codes: A61K 31/381 having five-membered rings
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 31/517 ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 31/5415 ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam
• CPC Class Codes: A61K 31/551 having two nitrogen atoms, e.g. dilazep
• CPC Class Codes: A61K 31/5513 1,4-Benzodiazepines, e.g. diazepam or clozapine
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia

Abstract

An antipsychotic and GlyT1 inhibitor combination is disclosed. The antipsychotic and GlyT1 inhibitor combination may be employed in the prevention and treatment of symptoms of schizophrenia. Pharmaceutical compositions and treatments comprising an antipsychotic and a GlyT1 inhibitor for treating symptoms of schizophrenia are thus also disclosed.

Claims

1. A method of treating or preventing a symptom of schizophrenia in a mammal, comprising administering an antipsychotic and a GlyT1 inhibitor to said mammal in an amount effective to treat or prevent said symptom of schizophrenia.

6. The method according to claim 1 wherein the antipsychotic is selected from the group consisting of olanzapine, haloperidol, fluphenazine, chlorpromazine, clozapine, risperidone, paliperidone, R209130, aripiprazole, and pharmaceutically acceptable salts thereof, pharmaceutically acceptable esters thereof and enantiomeric forms thereof.

7. The method according to claim 1 wherein the GlyT1 inhibitor is selected from the group consisting of:

2. A method of increasing extracellular glycine in a mammal, comprising administering an antipsychotic and a GlyT1 inhibitor to said mammal.

3. The method of claim 2, wherein said extracellular glycine is increased to an amount more than if said antipsychotic or said GlyT1 inhibitor was administered alone.

4. The method of claim 2, wherein said GlyT1 inhibitor has minimal or no effect on extracellular dopamine.

8. The method according to claim 3 wherein the antipsychotic is selected from the group consisting of olanzapine, haloperidol, fluphenazine, chlorpromazine, clozapine, risperidone, paliperidone, aripiprazole, and pharmaceutically acceptable salts thereof, pharmaceutically acceptable esters thereof and enantiomeric forms thereof.

5. A medical product, comprising (a) an antipsychotic, and (b) a GlyT1 inhibitor, as a combined preparation for simultaneous, separate or sequential use in treating or preventing a disorder that can present a symptom of schizophrenia.

9. A process for treating a psychotic disease in a mammal, comprising administering to said mammal an antipsychotic and a GlyT1 inhibitor in an amount effective to treat or prevent the clinical manifestations of said psychotic disease.

10. The process of claim 9 wherein the psychotic disease is selected from the group consisting of schizophrenia, dementia, depression, Alzheimer'"'"'s, ADHD, substance abuse and anxiety.