Use of ladostigil for the treatment of schizophrenia

Abstract

Disclosed are methods for the treatment of schizophrenia comprising administering an amount of R(+)-6-(N-methyl, N-ethyl-carbamoyloxy)-N′-propargyl-1-aminoindan or a pharmaceutically acceptable salt thereof.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1: Full Experiment—Means and standard errors of the log times to complete licks 76-100 (after tone onset) of the preexposed (PE) and nonpreexposed (NPE) rats treated with MK-801 or saline, and pretreated with ladostigil tartrate at doses of 25 mg/kg (low) or 37.5 mg/kg (high), or vehicle. Forty preexposures and five conditioning trials were used. Ladostigil tartrate was chronically administered perorally prior to the preexposure (day 10 of administration) and conditioning (day 11 of administration) stages; MK-801 was administered intraperitoneally prior to the conditioning stage. Asterisks indicate a significant difference between the PE and NPE groups, namely, presence of latent inhibition.

FIG. 2: Low Dose Experiment—Means and standard errors of the log times to complete licks 76-100 (after tone onset) of the preexposed (PE) and nonpreexposed (NPE) rats treated with MK-801 or saline, and pretreated with ladostigil tartrate at a dose of 25 mg/kg (low) or vehicle. Forty preexposures and five conditioning trials were used. Ladostigil tartrate was chronically administered perorally prior to the preexposure (day 10 of administration) and conditioning (day 11 of administration) stages; MK-801 was administered intraperitoneally prior to the conditioning stage. Asterisks indicate a significant difference between the PE and NPE groups, namely, presence of latent inhibition.

FIG. 3: High Dose Experiment—Means and standard errors of the log times to complete licks 76-100 (after tone onset) of the preexposed (PE) and nonpreexposed (NPE) rats treated with MK-801 or saline, and pretreated with ladostigil tartrate at a dose of 37.5 mg/kg (high) or vehicle. Forty preexposures and five conditioning trials were used. Ladostigil tartrate was chronically administered perorally prior to the preexposure (day 10 of administration) and conditioning (day 11 of administration) stages; MK-801 was administered intraperitoneally prior to the conditioning stage. Asterisks indicate a significant difference between the PE and NPE groups, namely, presence of latent inhibition.

Claims

1. A method of treating a symptom of schizophrenia in a subject afflicted with schizophrenia comprising administering to the subject an amount of R(+)-6-(N-methyl, N-ethyl-carbamoyloxy)-N′-propargyl-1-aminoindan or a pharmaceutically acceptable salt thereof effective to treat the symptom of schizophrenia.

2. The method of claim 1, wherein the subject is a human being.

3. The method of claim 1, wherein the symptom of the schizophrenia is a negative symptom/cognitive impairment.

4. The method of claim 1, wherein the administration is effected orally, parenterally, rectally or transdermally.

5. The method of claim 1, wherein the method comprises administering R(+)-6-(N-methyl, N-ethyl-carbamoyloxy)-N′-propargyl-1-aminoindan.

6. The method of claim 1, wherein the method comprises administering a pharmaceutically acceptable salt of R(+)-6-(N-methyl, N-ethyl-carbamoyloxy)-N′-propargyl-1-aminoindan.

7. The method of claim 6, wherein the pharmaceutically acceptable salt of R(+)-6-(N-methyl, N-ethyl-carbamoyloxy)-N′-propargyl-1-aminoindan is ½ tartrate.

8. The method of claim 7, wherein the amount of R(+)-6-(N-methyl, N-ethyl-carbamoyloxy)-N′-propargyl-1-aminoindan ½ tartrate is in the range from 0.5 mg to 2000 mg.

9. The method of claim 8, wherein the amount of R(+)-6-(N-methyl, N-ethyl-carbamoyloxy)-N′-propargyl-1-aminoindan ½ tartrate is in the range from 25 mg to 105 mg.

10. The method of claim 9, wherein the amount of R(+)-6-(N-methyl, N-ethyl-carbamoyloxy)-N′-propargyl-1-aminoindan ½ tartrate is 25 mg.

11. The method of claim 8, wherein the amount of R(+)-6-(N-methyl, N-ethyl-carbamoyloxy)-N′-propargyl-1-aminoindan ½ tartrate is 8.9 mg.

12. The method of claim 8, wherein the salt of R(+)-6-(N-methyl, N-ethyl-carbamoyloxy)-N′-propargyl-1-aminoindan is in crystalline form.

13. The method of claim 1, wherein the R(+)-6-(N-methyl, N-ethyl-carbamoyloxy)-N′-propargyl-1-aminoindan or the pharmaceutically acceptable salt thereof is in a pharmaceutical composition which also comprises at least one pharmaceutically acceptable carrier.

14. The method of claim 13, wherein the pharmaceutical composition is in the form of a tablet, capsule, pill, powder, or granule.

15. A pharmaceutical composition comprising R(+)-6-(N-methyl, N-ethyl-carbamoyloxy)-N′-propargyl-1-aminoindan or the pharmaceutically acceptable salt thereof and an agent which treats a symptom of schizophrenia.

16. The composition of claim 15, wherein the agent is chlorpromazine, thioridazine, mesoridazine, trifluoperazine, fluphenazine, perphenazine, loxapine, molindone, thiothixene, haloperidol, pimozide, clozapine, risperidone, olanzapine, quetiapine, sertindole, or ziprasidone.

17-18. (canceled)