Treatment of autism spectrum disorders, obsessive-compulsive disorder and anxiety disorders

1. A method of treating an NMDA receptor-mediated disorder in a subject in need thereof, comprising administering to the subject an effective amount of a chemical entity of formula II B′ :

wherein the chemical entity is selected from:

compound

Z B′

R 5B′

R 6B′

R 7B′

E1-22.2 B′

CH 3

H

H

E1-22.4 B′

F

H

H

E1-22.5 B′

CH 2 CH 3

H

H

E1-22.6 B′

CF 2 H

H

H

wherein the NMDA-receptor mediated disorder is selected from (i) an obsessive-compulsive disorder (OCD) and/or related disorder, (ii) an autism spectrum disorder (ASD), or (iii) an anxiety disorder.

2. The method according to claim 1 , wherein the NMDA receptor-mediated disorder is an obsessive-compulsive disorder (OCD) and/or related disorder.

3. The method according to claim 1 , wherein the NMDA receptor-mediated disorder is an autism spectrum disorder (ASD).

4. The method according to claim 1 , wherein the NMDA receptor-mediated disorder is an anxiety disorder.

5. The method according to claim 2 , wherein the OCD and/or related disorder is selected from body dysmorphic disorder (e.g., anorexia nervosa), hoarding disorder, trichotillomania and excoriation disorder.

6. The method according to claim 3 , wherein the ASD is characterized by one or more of repetitive or ritualistic behaviors, behavioral rigidity, constant movements, lack of social interaction, restricted patterns of interest that are abnormal in intensity or focus, or sensory abnormalities.

7. The method of claim 3 , wherein the autism spectrum disorder is autism, Asperger's syndrome, or pervasive developmental disorder not otherwise specified (PDD-NOS).

8. The method of claim 4 , wherein the anxiety disorder is generalized anxiety disorder.

9. The method of claim 4 , wherein the anxiety disorder is agoraphobia with panic disorder.

10. The method of claim 4 , wherein the anxiety disorder is agoraphobia without panic disorder.

11. The method of claim 4 , wherein the anxiety disorder is panic disorder.

12. The method of claim 4 , wherein the anxiety disorder is post-traumatic stress disorder.

13. The method of claim 4 , wherein the anxiety disorder is social anxiety disorder.

14. The method of claim 1 , wherein the NR2B subunit-selective NMDA antagonist is administered intravenously or intracranially.

15. The method of claim 1 , further comprising administering to the subject an effective amount of a therapeutic agent useful for treating an anxiety disorder.

16. The method of claim 15 , wherein the therapeutic agent is a selective serotonin reuptake inhibitor, a tri-cyclic antidepressant, a benzodiazepine, an atypical antipsychotic or a serotonin-norepinephrine reuptake inhibitor.

17. The method of claim 1 , wherein the chemical entity is administered in conjunction with behavioral therapy, electroconvulsive therapy, deep brain stimulation, or vagus nerve stimulation.

18. The method of claim 1 , further comprising administering to the subject an effective amount of a therapeutic agent useful for treating an autism spectrum disorder.

19. The method of claim 18 , wherein the therapeutic agent is an atypical antipsychotic, a dopamine receptor agonist, a selective serotonin reuptake inhibitor, an atypical antipsychotic, a serotonin-norepinephrine reuptake inhibitor, a stimulant, secretin, oxytocin, or a typical antipsychotic.

20. The method of claim 1 , wherein the chemical entity is administered in conjunction with behavioral therapy, electroconvulsive therapy, or hyperbaric oxygen therapy.

21. The method of claim 1 , wherein the subject is a human.

22. The method according to claim 1 , wherein the chemical entity is in a salt form.

23. The method according to claim 22 , wherein the chemical entity is in a pharmaceutically acceptable salt form.

24. The method according to claim 1 , wherein the chemical entity is:

25. A chemical entity selected from: