Methods for treating depressive symptoms
View Patent ↗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.
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: