Methods for treating depressive symptoms

• US 10,231,963 B2
• Filed: 04/17/2017
• Issued: 03/19/2019
• Est. Priority Date: 05/24/2013
• Status: Active Grant

• Current Assignee: Alkermes Pharma Ireland Limited (Alkermes plc)
• Original Assignee: Alkermes Pharma Ireland Limited (Alkermes plc)
• Inventors: Blumberg, Laura Cook, Deaver, Daniel R., Eyerman, David J., Wynn, Thomas Andrew
• Primary Examiner(s): Weddington, Kevin E
• Application Number:
  US15/489,377
• Publication Number:
  US 20170216279A1
• Time in Patent Office: 701 Days
• Field of Search: 514289
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: C07D 211/62 attached in position 4
• CPC Class Codes: C07D 217/04 with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
• CPC Class Codes: C07D 221/22 Bridged ring systems
• CPC Class Codes: C07D 221/28 Morphinans
• CPC Class Codes: C07D 223/04 with only hydrogen atoms, halogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 405/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 489/00 Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula:
• CPC Class Codes: C07D 489/09 containing 4aH-8, 9 c-Iminoethano- phenanthro [4, 5-b, c, d] furan ring systems condensed with carbocyclic rings or ring systems

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.

Claims

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 GTPγ

S 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.

4. The method of claim 1, wherein the μ

opioid receptor agonist is a compound of Formula II;

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

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 GTPγ

S 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.

6. The method of claim 2, wherein the μ

opioid receptor agonist is a compound of Formula II;

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

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 GTPγ

S 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.

8. The method of claim 3, wherein the μ

opioid receptor agonist is a compound of Formula II;

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