WO2002043727A1

WO2002043727A1 - Treatment of psychiatric disorders with trimethyl-bicyclo[2.2.1]heptane derivatives

Info

Publication number: WO2002043727A1
Application number: PCT/FI2001/001032
Authority: WO
Inventors: Outi MÄKI-IKOLA
Original assignee: Orion Corporation
Priority date: 2000-11-28
Filing date: 2001-11-27
Publication date: 2002-06-06
Also published as: AU2002218338A1

Abstract

A method for the treatment of psychiatric disorders with impaired social behaviour in a mammal by administering to the mammal an effective amount of 1,7,7-trimethylbicyclo[2.2.1]heptane derivative of Formula I wherein R is hydrogen or methyl, or a pharmaceutically acceptable salt thereof.

Description

TREATMENT OF PSYCHIATRIC DISORDERS WITH TRIMETHYL- BICYLO [2.2.1 ] HEPTANE DERIVATIVES

FIELD OF THE INVENTION

The present invention relates in general to a method for treatment of psychiatric disorders with impaired social behaviour. More particularly, this invention relates to a method for treatment of psychiatric disorders with impaired social behaviour in a mammal by administering to the mammal an effective amount of 1,7,7- trimethylbicyclo[2.2.1]heptane derivative of Formula I

wherein R is hydrogen or methyl, or a pharmaceutically acceptable salt thereof.

Additional objects and advantages of the invention will be set forth in part in the description which follows, and in part will be obvious from the description, or may be learned by practice of the invention. The objects and advantages of the invention will be realised and attained by means of the elements and combinations particularly pointed out in the appended claims.

BACKGROUND OF THE INVENTION

Psychiatric disorders with impaired social behaviour, such as Social Anxiety Disorder (SAD), Panic Disorder (PD), and agoraphobia are chronic anxiety disorders in which the anxiety is usually related to social situations. As a consequence, anticipatory anxiety and avoidant or phobic behaviour may develop and the social adjustment of the patient is impaired.

Psychiatric disorders with impaired social behaviour, such as SAD, PD, and agoraphobia, may appear as a single disorder or more typically they are comorbid conditions with an affective disorder, e.g., depression, or an other anxiety disorder, such as generalized anxiety disorder (GAD).

The active ingredients of this invention, (lR,2S,4R)-(-)- 2-phenyl 2- (dimethylaminoethoxy)-l,7,7-trimethyl-bicyclo[2.2.1]heptane, known as deramciclane, and (lR,2S,4R)-(-)- 2-phenyl-2-(methylaminoethoxy)-l,7,7-trimethyl- bicyclo[2.2.1]heptane, and their pharmaceutically acceptable acid addition salts with inorganic and organic acids generally used for the purpose, fall within the disclosures of U.S. Patent No. 4,342,762 and International Patent Application No. WO 98/17230, respectively, which are both incorporated herein by reference.

These compounds are selective serotonin 5HT2A- and/or 5HT2C-receptor antagonists. They have shown anxiolytic-like effects in animal test models.

BRIEF DESCRIPTION OF THE DRAWING

Figure 1 shows the social contacts of the patients at visit 8.

DESCRIPTION OF THE INVENTION

Applicants have surprisingly discovered that the compounds of formula (I) are effective in reducing one or several symptoms associated with psychiatric disorders with impaired social behaviour in a mammal. Accordingly, an object of the present invention is a method for treating psychiatric disorders with impaired social behaviour in a mammal by administering to the mammal an effective amount of a compound of Formula (I) or a pharmaceutically acceptable salt thereof. Specifically, the psychiatric disorder with impaired social behaviour is PD, SAD or agoraphobia. Another object of the invention is a method for treating psychiatric disorders with impaired social behaviour in a mammal by administering to the mammal an effective amount of a compound of Formula (I) or a pharmaceutically acceptable salt thereof together with a benzodiazepine or an antidepressant. The antidepressant may be a tricyclic antidepressant, such as clomipramine, a SSRI, such as fiuoxetine or paroxetine, or a SNRI, such as venlafaxine.

For the purposes of this disclosure and claims the term "treatment" is relating to treatment in order to cure or alleviate the disease or its symptoms, and to treatment in order to prevent the development or the exacerbation of the disease or its symptoms.

Pharmaceutically acceptable salts of the compound of Formula (I) can be formed with inorganic acids, e.g. hydrohalogenic acid such as hydrochlorid acid or hydrobromic acid, sulfuric acid, phosphoric acid or nitric acid, or organic acids e.g., tartaric acid, succinic acid, malic acid, maleic acid, fumaric acid, citric acid, or lactic acid. Salt with fumaric acid is preferred.

Pharmaceutical compositions containing a compound of Formula (I) or a pharmaceutically acceptable salt thereof as the active ingredient include the usual oral dosage forms, such as tablets, capsules, and liquid preparations. In oral dosage forms, the active ingredient can be mixed with suitable pharmaceutically acceptable excipients, such as starch, lactose, sucrose and magnesium stearate, in accordance with conventional pharmaceutical practice.

The precise amount of the drug to be administered to a mammal for treating psychiatric disorders with social disturbances e.g. panic disorder in a mammal is dependent on numerous factors known to one skilled in the art, such as the compund to be administered, the general condition of the patient, the condition to be treated etc. For example, the usual recommended oral daily dose of deramciclane would be about 5-150 mg, preferably 30-60 mg.

The invention will be further clarified by the following example, which is intended to be purely exemplary of the invention. EXAMPLE

The efficacy of deramciclane in the treatment of psychiatric disorders with impaired social behaviour was studied in a randomised placebo-controlled double-blind study. The subjects were randomly assigned to four parallel groups to receive one tablet twice daily (b.i.d) of a placebo, 5mg (=10mg/day), 15mg (=30mg/day), or 30mg (=60mg/day) deramciclane for 8 weeks.

After 8 weeks treatment the patients were questioned whether their social contact situation was better or worse than before the treatment.

RESULTS

Administration of deramciclane improved the quality of social behaviour as assessed with evaluation of social contacts. The amount of patients reporting improved social contacts was 12%, 16%, 20% and 28% of patients in placebo, 5 mg b.i.d, 15 mg b.i.d, and 30 mg b.i.d. groups, respectively. The improvement was statistically significant (p=0.048, Mantel-Haenszel model) in group receiving deramciclane 30 mg b.i.d. when compared to placebo. The results are presented also in Figure 1.

Although the invention has been illustrated by the preceding example, it is not to be construed as being limited to the materials employed therein; rather, the invention is directed to the generic area as herein disclosed. Various modifications and embodiments thereof can be made without departing from the spirit or scope thereof.

Claims

CLAIMS:

1. Use of a compound of Formula (I)

wherein R is hydrogen or methyl, or a pharmaceutically acceptable ester or salt thereof, for the manufacture of a medicament for treating psychiatric disorders with impaired social behaviour in a mammal.

2. The use of claim 1, wherein the disorder is Social Anxiety Disorder.

3. The use of claim 1 , wherein the disorder is Panic Disorder.

4. The use of claim 1 , wherein the disorder is agoraphobia.

5. The use of claim 1, wherein the psychiatric disorder with impaired social behaviour is a comorbidity of depression.

6. The use of claim 1, wherein the psychiatric disorder with impaired social behaviour is a comorbidity of Generalized Anxiety Disorder.

7. The use of claim 1, wherein the mammal is human.

8. The use of claim 1, wherein the compound is deramciclane or a pharmaceutically acceptable ester or salt thereof.

9. The use of claim 1, wherein the effective dose of the medicament is about 5-150 mg/day.

10. The use of claim 9 wherein the effective dose of the medicament is about 10-60 mg/day.

11. The use of claim 1 , further comprising administering a benzodiazepine together with the compound of Formula (I) or pharmaceutically acceptable salt thereof.

12. The use of claim 1, further comprising administering an antidepressant together with the compound of Formula (I) or pharmaceutically acceptable salt thereof.