Treatment of mood disorders with functional antagonists of the glycine/NMDA receptor complex

• US 5,086,072 A
• Filed: 06/18/1990
• Issued: 02/04/1992
• Est. Priority Date: 06/18/1990
• Status: Expired due to Term

• Current Assignee: United States Department Of Health And Human Services
• Original Assignee: United States Department Of Health And Human Services
• Inventors: Trullas, Ramon, Skolnick, Phil
• Primary Examiner(s): Waddell, Frederick E.
• Assistant Examiner(s): NOT, DEFINED
• Application Number:
  US07/541,032
• Time in Patent Office: 596 Days
• Field of Search: 514/531, 514/557
• US Class Current: 514/531
• CPC Class Codes: A61K 31/135 having aromatic rings , e.g. ketamine, nortriptyline methadone A61K31/137
• CPC Class Codes: A61K 31/195 having an amino group
• CPC Class Codes: A61K 31/215 of carboxylic acids
• CPC Class Codes: A61K 31/66 Phosphorus compounds
• CPC Class Codes: A61K 31/675 having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 25/26 Psychostimulants, e.g. nicotine, cocaine

Abstract

A method is disclosed for the treatment of mood disorders, including major depression, by administering an effective mood disorder treating amount of a compound possessing functional antagonist properties for the N-methyl-D-aspartate receptor complex.

Claims

1. A method for treating mood disorders selected from the group consisting of major depression, bipolar disorder, dysthemia, and seasonal effective disorder in a patient, which comprises:

administering to a patient in need thereof, an effective amount of a compound possessing functional antagonist properties for the N-Methyl-D-Aspartate (NMDA) receptor complex.

2. The method of claim 1, wherein said mood disorder is major depression.

3. The method of claim 1, wherein the compound which is administered possesses partial agonist properties for the strychnine-insensitive glycine modulatory site of the NMDA receptor complex.

4. The method of claim 1, wherein the compound which is administered possesses partial agonist properties for the strychnine-insensitive glycine modulatory site of the NMDA receptor complex, and is a compound having the formula:

##STR3## wherein A is --NH₂, --NHR¹ or --NR¹ R² ;

B is --OH or --OR³ ;

R¹, R² and R³, same or different, are lower alkyl, or lower alkyl substituted by halogen, hydroxyl, alkoxy, oxo, mercapto, aryl or amino;

or a pharmaceutically acceptable salt thereof.

5. The method of claim 1, wherein the compound which is administered possesses partial agonist properties for the strychnine-insensitive glycine modulatory site of the NMDA receptor complex, and is a compound having the formula:

##STR4## wherein A¹ is --NH₂, --NHR¹ or --NR¹ R² ;

B¹ is --OH or --OR³ ;

R¹, R² and R³, same or different are lower alkyl, or a pharmaceutically acceptable salt thereof.

6. The method of claim 4, wherein the compound is:

1-aminocyclopropanecarboxylic acid,

1-aminocyclopropanecarboxylic acid methyl ester,

1-aminocyclopropanecarboxylic acid ethyl ester, or

a pharmaceutically acceptable salt thereof.

7. The method of claim 5, wherein the compound is:

1-aminocyclopropanecarboxylic acid,

1-aminocyclopropanecarboxylic acid methyl ester,

1-aminocyclopropanecarboxylic acid ethyl ester or

the pharmaceutically acceptable salts thereof.

8. A method for treating major depression in a patient, comprising:

administering to a patient in need thereof an effective amount of a functional antagonist of the N-methyl-D-aspartate (NMDA) receptor complex;

administering to a patient in need thereof an effective amount of a functional antagonist of the N-methyl-D-aspartate (NMDA) receptor complex;

the functional antagonist which is administered being selected from the group consisting of;

1-aminocyclopropylcarboxylic acid;

1-aminocyclopropylcarboxylic acid methyl ester;

1-aminocyclopropylcarboxylic acid ethyl ester; and

the pharmaceutically acceptable salts thereof.

9. The method of claim 8, wherein the functional antagonist which is administered is 1-aminocyclopropanecarboxylic acid;

or a pharmaceutically acceptable salt thereof.

10. The method of claim 8, wherein the functional antagonist which is administered is 1-aminocyclopropanecarboxylic acid methyl ester.