Methods for treating depressive symptoms
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 μ opioid receptor agonist, wherein the μ opioid receptor agonist is compound of Formula III:
or a pharmaceutically acceptable salt thereof, wherein
R 1 is C 1 -C 6 alkyl, C 2 -C 6 alkenyl, aryl, cycloalkyl, heterocyclyl, benzyl, hydroxyalkyl, or alkoxyalkyl;
R 1a is H or methyl;
R 2 and R 3 are each H, methyl, or ethyl, or alternatively, R 2 and R 3 , together with the carbon atoms to which they are attached, form a 6-membered unsubstituted carbocyclic ring or carbonyl-substituted carbocyclic ring;
R 4 and R 5 are each, independently, H, hydroxyl, or C 1 -C 6 alkyl;
R 6 is unsubstituted or substituted C 6 -C 10 aryl, or substituted or unsubstituted heteroaryl comprising one or two 5- or 6-membered rings and 1-4 heteroatoms selected from N, O and S;
R 7 and R 8 are each, independently, H or hydroxyl; and
wherein the depressive symptom is depressed mood, loss of pleasure, loss of appetite, sleep disturbance, psychomotor changes, fatigue, or post-partum depression.
2. The method according to claim 1 , wherein the compound of Formula III 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, wherein the μ opioid receptor agonist is compound of Formula III:
or a pharmaceutically acceptable salt thereof, wherein
R 1 is C 1 -C 6 alkyl, C 2 -C 6 alkenyl, aryl, cycloalkyl, heterocyclyl, benzyl, hydroxyalkyl, or alkoxyalkyl;
R 1a is H or methyl;
R 2 and R 3 are each H, methyl, or ethyl, or alternatively, R 2 and R 3 , together with the carbon atoms to which they are attached, form a 6-membered unsubstituted carbocyclic ring or carbonyl-substituted carbocyclic ring;
R 4 and R 5 are each, independently, H, hydroxyl, or C 1 -C 6 alkyl;
R 6 is unsubstituted or substituted C 6 -C 10 aryl, or substituted or unsubstituted heteroaryl comprising one or two 5- or 6-membered rings and 1-4 heteroatoms selected from N, O and S; and
R 7 and R 8 are each, independently, H or hydroxyl,
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, or Trichotillomania.
4. The method of claim 3 , wherein the compound of Formula III is:
5. 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, wherein the μ opioid receptor agonist is compound of Formula III:
or a pharmaceutically acceptable salt thereof, wherein
R 1 is C 1 -C 6 alkyl, C 2 -C 6 alkenyl, aryl, cycloalkyl, heterocyclyl, benzyl, hydroxyalkyl, or alkoxyalkyl;
R 1a is H or methyl;
R 2 and R 3 are each H, methyl, or ethyl, or alternatively, R 2 and R 3 , together with the carbon atoms to which they are attached, form a 6-membered unsubstituted carbocyclic ring or carbonyl-substituted carbocyclic ring;
R 4 and R 5 are each, independently, H, hydroxyl, or C 1 -C 6 alkyl;
R 6 is unsubstituted or substituted C 6 -C 10 aryl, or substituted or unsubstituted heteroaryl comprising one or two 5- or 6-membered rings and 1-4 heteroatoms selected from N, O and S; and
R 7 and R 8 are each, independently, H or hydroxyl, wherein the depressive symptom is an anxiety disorder, wherein the anxiety disorder is generalized anxiety disorder, panic, agoraphobia, acute stress, or post-traumatic stress disorder.
6. The method of claim 5 , wherein the compound of Formula III is: