DEUTERATED ANALOGS OF D-SERINE AND USES THEREOF

1 . A pharmaceutical composition comprising a compound of Formula I:

wherein

R 1 is —OH, —OD, —O—C 1-4 alkyl, or an amino acid residue;

R 2 is H, D, —C 1-4 alkyl, —C(O)—C 1-6 alkyl, or —C(O)—C 1-6 hydroxyalkyl;

R 3 is H, D, or an amino acid residue;

R 4 is H or D; and

each of Y 1 , Y 2a , Y 2b is independently H or D, provided that at least one of Y 1 , Y 2a Y 2 b is D; wherein each position designated specifically as deuterium has at least 50.1% incorporation of deuterium;

or a pharmaceutically acceptable salt thereof;

and a pharmaceutically acceptable carrier.

2 . The pharmaceutical composition of claim 1 , wherein R 1 or R 3 is a D-D-serine residue.

3 . The pharmaceutical composition of claim 1 , wherein the compound is a compound of Formula II :

wherein each of Y 1 , Y 2a Y 2b is independently H or D, provided that at least one of Y 1 , Y 2a and Y 2b is D;

or a pharmaceutically acceptable salt thereof.

4 . The pharmaceutical composition of claim 3 , wherein Y 1 is D.

5 . The pharmaceutical composition of any one of claims 1 - 4 , wherein Y 2a and Y 2b are each H.

6 . The pharmaceutical composition of any one of claims 1 - 4 , wherein Y 2a and Y 2b are each D.

7 . The pharmaceutical composition of claim 1 , wherein the compound is selected from Compound 100 and Compound 103:

8 . The pharmaceutical composition of claim 1 , wherein the compound is Compound 100:

9 . The pharmaceutical composition of any one of claims 1 - 8 , wherein each position designated specifically as deuterium has at least 90% incorporation of deuterium.

10 . The pharmaceutical composition of any one of claims 1 - 9 , wherein any atom not designated as deuterium is present at its natural isotopic abundance.

11 . The pharmaceutical composition of any one of claims 1 - 10 , wherein the compound of Formula I is at least about 90% stereomerically pure.

12 . The pharmaceutical composition of any one of claims 1 - 11 , wherein the pharmaceutical composition is suitable for oral administration.

13 . The pharmaceutical composition of any one of claims 1 - 12 , wherein the pharmaceutical composition comprises 0.1 g to 60 g of the compound of Formula I.

14 . The pharmaceutical composition of any one of claims 1 - 13 , wherein the pharmaceutical composition further comprises an antipsychotic.

15 . A method of treating NMDAR encephalitis, the method comprising administering to a subject in need thereof an effective amount of the pharmaceutical compositions of any one of claims 1 - 13 .

16 . A method of treating epilepsy, NMDAR encephalitis, Parkinson's disease, cognitive deficits in Parkinson's disease, Alzheimer's disease, mild cognitive impairment, amyotrophic lateral sclerosis (ALS), Huntington's disease, schizophrenia, bipolar disorder, bipolar mania, bipolar depression, treatment-refractory depression, cognitive deficits in depression, major depressive disorder, generalized anxiety disorder, major depressive disorder with mixed features, and cognition deficits associated with Huntington's disease, subjective cognitive decline, traumatic brain injury, or Lewy Body Dementia, the method comprising administering to a subject in need thereof an effective amount of the pharmaceutical composition of any one of claims 1 - 13 .

17 . A method of treating depression, the method comprising administering to a subject in need thereof an effective amount of the pharmaceutical composition of any one of claims 1 - 13 .

18 . A method of increasing NMDA receptor function, the method comprising contacting a cell with the pharmaceutical composition of any one of claims 1 - 13 , such that NMDA receptor function in the cell is increased.

19 . A method of treating schizophrenia, the method comprising administering to a subject in need thereof an effective amount of the pharmaceutical composition of any one of claims 1 - 14 .

20 . The method of claim 19 , wherein the method further comprises administering an antipsychotic therapeutic agent to the subject.