Methods

Patent metadata

Field	Value
Publication number	US-12414948-B2
Application number	US-202318518436-A
Country	US
Kind code	B2
Filing date	Nov 22, 2023
Priority date	May 18, 2022
Publication date	Sep 16, 2025
Grant date	Sep 16, 2025

Abstract

The disclosure provides methods the treatment of psychiatric disorders caused by viral, bacterial, or autoimmune encephalitis, and for treatment of psychiatric symptoms of viral, bacterial, and autoimmune encephalitis, and for protecting or reinforcing the blood-brain barrier, comprising administering to a patient in need thereof, a therapeutically effective amount of a 5-HT 2A .

First claim

We claim:

1. A method for the treatment of psychiatric disorders caused by viral, bacterial, or autoimmune encephalitis, and for treatment of psychiatric symptoms of viral, bacterial, and autoimmune encephalitis comprising administering to a patient in need thereof a Compound of Formula I:

wherein:
X is —N(CH 3 )—; and
Y is —C(═O)—;
in free base, or pharmaceutically acceptable salt form;
wherein the patient has elevated levels of one or more biomarkers indicative of peripheral inflammation in the blood, plasma, serum, peripheral blood mononuclear cells (PBMC), or urine; and
wherein the psychiatric disorder and/or the psychiatric symptom is depression, anxiety, psychosis, anhedonia, memory loss, impairment of executive functioning, difficulty concentrating, seizures, difficulty sleeping, hallucination, change in personality, or any combination thereof.

2. The method according to claim 1 , wherein the Compound of Formula I is in the form of a tosylate salt.

3. The method according to claim 1 , wherein the method comprises once daily administration of a unit dosage for oral administration, comprising the compound of Formula I in free base or in tosylate salt form, in an amount equivalent 1 to 100 mg of free base, and a pharmaceutically acceptable diluent or carrier.

4. The method according to claim 1 , wherein the method comprises once daily administration of a unit dosage for oral transmucosal administration selected from a sublingual or buccal orally disintegrating tablet, wafer, or film, comprising the compound of Formula I in free base or in tosylate salt form, in an amount equivalent to 0.5 to 30 mg of free base, and a pharmaceutically acceptable diluent or carrier.

5. The method according to claim 1 , wherein the compound of Formula I is administered in the form of a long-acting injectable (LAI) composition.

6. The method according to claim 1 , wherein the encephalitis is viral encephalitis.

7. The method according to claim 6 , wherein the encephalitis is caused by, or suspected to be caused by, Herpes simplex Virus 1, Herpes Simplex Virus 2, West Nile Virus, Nipah Virus, human immunodeficiency virus, rabies virus, Epstein-Barr Virus, cytomegalovirus, coronavirus, or influenza virus.

8. The method according to claim 1 , wherein the encephalitis is bacterial encephalitis.

9. The method according to claim 8 , wherein the encephalitis is caused by, or believed to be caused by, toxoplasmosis, Rickettsia, Mycoplasma, Borrelia (e.g., Lyme disease), or malaria.

10. The method according to claim 1 , wherein the encephalitis is autoimmune encephalitis.

11. The method according to claim 10 , wherein the encephalitis is caused by, or believed to be caused by, autoantibodies against the NMDA receptor, the AMPA receptor, the voltage-gated potassium, channel (VGKC), the LGL1 protein, the GABA receptor, the glycine receptor, the glutamate receptor, or the CASPR2 receptor.

12. The method according to claim 1 , wherein the psychiatric disorder and/or the psychiatric symptom is acute depression, depression of MDD, depression of bipolar disorder, acute anxiety, schizophrenia, anhedonia, or any combination thereof.

13. The method according to claim 1 , wherein the method protects or reinforces the blood-brain barrier.

14. The method according to claim 1 , wherein the patient has elevated levels of pro-inflammatory cytokines in the CNS, or elevated levels of C-reactive protein (CRP) of Csf1, and/or depressed levels of anti-inflammatory cytokines in the CNS.

15. The method according to claim 1 , wherein the compound of Formula I is administered intra-nasally subcutaneously, intramuscularly, intravenously, orally, sub-lingually, intra-peritoneally, or buccally.

16. The method according to claim 1 , wherein the patient has not responded to, or has not responded adequately to, or who suffers undesirable side effects from, treatment with another antidepressant agent.

17. A method for protecting or reinforcing the blood-brain barrier, comprising administering to a patient in need thereof, a therapeutically effective amount of a Compound of Formula I:

wherein:
X is —N(CH 3 )—; and
Y is —C(═O)—;
in free base, or pharmaceutically acceptable salt form;
wherein the patient has elevated levels of one or more biomarkers indicative of peripheral inflammation in the blood, plasma, serum, peripheral blood mononuclear cells (PBMC), or urine.

18. A method for the treatment of psychiatric disorders in a patient in need thereof, wherein the psychiatric disorder and/or the psychiatric symptom is depression, anxiety, psychosis, anhedonia, memory loss, impairment of executive functioning, difficulty concentrating, seizures, difficulty sleeping, hallucination, change in personality, or any combination thereof;
wherein the patient has elevated levels of one or more biomarkers indicative of peripheral inflammation in the blood, plasma, serum, peripheral blood mononuclear cells (PBMC), or urine; and
wherein the patient has elevated levels of pro-inflammatory cytokines in the CNS, or elevated levels of C-reactive protein (CRP), or Csf1, and/or depressed levels of anti-inflammatory cytokines in the CNS, the method comprising administering a therapeutically effective amount of a Compound of Formula I:

wherein:
X is —N(CH 3 )—; and
Y is —C(═O)—;
in free base, or pharmaceutically acceptable salt form,
to the patient.

19. The method according to claim 1 , wherein the one or more biomarkers indicative of peripheral inflammation are selected from the group consisting of interferon-alpha, interferon-beta, interferon-delta, and combinations thereof.

20. The method according to claim 1 , wherein after treatment with the Compound of Formula I, the patient has a reduced level of the one or more biomarkers indicative of peripheral inflammation.

21. The method according to claim 1 , wherein the patient has peripheral serotonin deficiency.

22. The method according to claim 17 , wherein the one or more biomarkers indicative of peripheral inflammation are selected from the group consisting of interferon-alpha, interferon-beta, interferon-delta, and combinations thereof.

23. The method according to claim 17 , wherein after treatment with the Compound of Formula I, the patient has a reduced level of the one or more biomarkers indicative of peripheral inflammation.

24. The method according to claim 17 , wherein the patient has peripheral serotonin deficiency.

25. The method according to claim 18 , wherein the one or more biomarkers indicative of peripheral inflammation are selected from the group consisting of interferon-alpha, interferon-beta, interferon-delta, and combinations thereof.

26. The method according to claim 18 , wherein after treatment with the Compound of Formula I, the patient has a reduced level of the one or more biomarkers indicative of peripheral inflammation.

27. The method according to claim 18 , wherein the patient has peripheral serotonin deficiency.

Assignees

• Intra Cellular Therapies Inc

Inventors

• Dutheil Sophie
• Snyder Gretchen
• Li Peng
• Davis Robert E

Classifications

• A61P25/22 Primary

  Anxiolytics · CPC title

• A61P25/24

  Antidepressants · CPC title

• A61P25/18

  Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• A61K31/4985 Primary

  Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems · CPC title