Methods for treating depressive symptoms

Patent metadata

Field	Value
Publication number	US-10231963-B2
Application number	US-201715489377-A
Country	US
Kind code	B2
Filing date	Apr 17, 2017
Priority date	May 24, 2013
Publication date	Mar 19, 2019
Grant date	Mar 19, 2019

Abstract

The present application relates methods for treating a depressive symptom comprising administering an effective amount of a μ opioid receptor agonist or a pharmaceutically acceptable salt thereof to a subject in need thereof. Non-limiting examples of such agonist include the compounds of Formulas I, II, III, and IV, as well as the compounds of Table A.

First claim

What is claimed is:

1. A method of treating a depressive symptom in a subject in need thereof, the method comprising administering to the subject an effective amount of a p opioid receptor agonist that exhibits an Emax of 5% to 45% in a GTPγS binding assay wherein the depressive symptom is depressed mood, loss of pleasure, loss of appetite, sleep disturbance, psychomotor changes, fatigue, and/or post-partum depression.

2. A method of treating a depressive symptom in a subject in need thereof, the method comprising administering to the subject an effective amount of a μ opioid receptor agonist that exhibits an Emax of 5% to 45% in a GTPγS binding assay wherein the depressive symptom is acute stress disorder, adjustment disorders with depressed mood, Asperger syndrome, attention deficit, bereavement, bipolar I disorder, bipolar II disorder, borderline and personality disorder, cyclothymia and dysthymia, depression such as major depressive disorder (MDD) and treatment-resistant disorder (TRD), Dysthymic disorder, hyperactivity disorder, impulse control disorder, mixed mania, obsessive-compulsive personality disorder (OCD), paranoid, post-traumatic stress disorder, seasonal affective disorder, self-injury separation, sleep disorder, substance-induced mood disorder, Tourette syndrome and tic disorder, and/or Trichotillomania.

3. A method of treating a depressive symptom in a subject in need thereof, the method comprising administering to the subject an effective amount of a μ opioid receptor agonist that exhibits an Emax of 5% to 45% in a GTPγS binding assay wherein the depressive symptom is an anxiety disorder, wherein the anxiety disorder is generalized anxiety disorder, panic, agoraphobia, acute stress, and/or post-traumatic stress disorder.

4. The method of claim 1 , wherein the μ opioid receptor agonist is a compound of Formula II:

or a pharmaceutically acceptable salt thereof, wherein
R 1 is C 1 -C 6 alkyl, C 2 -C 6 alkenyl, cycloalkyl, heterocyclyl, hydroxyalkyl, or alkoxyalkyl;
R 1a is H or methyl;
R 2 and R 3 are each methyl, or alternatively, R 2 and R 3 , together with the carbon atoms to which they are attached, form a 6-membered unsubstituted carbocyclic ring;
when is a single bond, R 4 is H; and
when is a double bond, R 4 is O.

5. The method according to claim 4 , wherein the compound of Formula II is:

6. The method of claim 2 , wherein the μ opioid receptor agonist is a compound of Formula II:

or a pharmaceutically acceptable salt thereof, wherein
R 1 is C 1 -C 6 alkyl, C 2 -C 6 alkenyl, cycloalkyl, heterocyclyl, hydroxyalkyl, or alkoxyalkyl;
R 1a is H or methyl;
R 2 and R 3 are each methyl, or alternatively, R 2 and R 3 , together with the carbon atoms to which they are attached, form a 6-membered unsubstituted carbocyclic ring;
when is a single bond, R 4 is H; and
when is a double bond, R 4 is O.

7. The method according to claim 6 , wherein the compound of Formula II is:

8. The method of claim 3 , wherein the μ opioid receptor agonist is a compound of Formula II:

or a pharmaceutically acceptable salt thereof, wherein
R 1 is C 1 -C 6 alkyl, C 2 -C 6 alkenyl, cycloalkyl, heterocyclyl, hydroxyalkyl, or alkoxyalkyl;
R 1a is H or methyl;
R 2 and R 3 are each methyl, or alternatively, R 2 and R 3 , together with the carbon atoms to which they are attached, form a 6-membered unsubstituted carbocyclic ring;
when is a single bond, R 4 is H; and
when is a double bond, R 4 is O.

9. The method according to claim 8 , wherein the compound of Formula II is:

Assignees

• Alkermes Pharma Ireland Ltd

Inventors

• Blumberg Laura Cook
• Deaver Daniel R
• Eyerman David J
• Wynn Thomas Andrew

Classifications

• A61P25/24

  Antidepressants · CPC title

• C07D217/04

  with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom · CPC title

• C07D211/62

  attached in position 4 · CPC title

• A61K31/485 Primary

  Morphinan derivatives, e.g. morphine, codeine · CPC title

• C07D405/12

  linked by a chain containing hetero atoms as chain links · CPC title