# US 11,304,917 B2 · Treatment of tinnitus using glutamate receptor agonists

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- Number: US 11,304,917 B2
- Document ID: US11304917B2
- Status: Granted
- Kind: B2
- Application number: 15/999,753
- Filed: 2016-02-19
- Published: 2021-08-19
- Granted: 2022-04-19
- Earliest claimed: 2016-02-19
- Assignees: Northeast Ohio Medical University
- Applicants: Northeast Ohio Medical University
- Inventors: Alexander V. Galazyuk
- Web page: https://patentgrep.com/patent/US11304917B2

## CPC

- A61K 31/196: the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
- A61K 31/662: Phosphorus acids or esters thereof having P—C bonds, e.g. foscarnet, trichlorfon
- A61K 31/343: condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 27/16: Otologicals
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

A method of treating tinnitus in a subject is described that includes administering a therapeutically effective amount of a group II metabotropic glutamate receptor (mGluR) agonist to the subject. A method of screening a subject having tinnitus for treatment with a group II mGluR agonist that includes testing the use of residual inhibition to suppress tinnitus in the subject, wherein suppression of tinnitus by residual inhibition indicates that a group II mGluR agonist would be effective for treating tinnitus in the subject, is also described.

## Claims

### Claim 1

A method of temporarily suppressing tinnitus in a subject, comprising administering a therapeutically effective amount of a group II metabotropic glutamate receptor (mGluR) agonist to the subject.

### Claim 2 (depends on 1)

The method of claim 1, wherein the group II mGluR agonist is selected from the group consisting of (1S,3R)-ACPD, cis-ACPD, (±)-trans-ACPD, (2R,4R)-APDC, (S)-3-Carboxy-4-hydroxyphenylglycine, (S)-4-Carboxy-3-hydroxyphenylglycine, (S)-4-Carboxyphenyglycine, L-CCG-I, DCG IV, LY354740, LY379268, (±)-LY395756, MAP4, NPEC-caged-LY379268, and spaglumic acid, and pharmaceutically acceptable salts thereof.

### Claim 3 (depends on 1)

The method of claim 1, wherein the group II mGluR agonist is LY354740 or an LY354740 prodrug, or a pharmaceutically acceptable salt thereof.

### Claim 4 (depends on 3)

The method of claim 3, wherein the subject is human, and a dose of LY354740 from about 100 to 200 mg/day is administered.

### Claim 5 (depends on 1)

The method of claim 1, wherein the group II mGluR agonist is administered systemically.

### Claim 6 (depends on 1)

The method of claim 1, wherein the group II mGluR agonist is administered with a pharmaceutically acceptable carrier.

### Claim 7 (depends on 1)

The method of claim 1, wherein the tinnitus is subjective tinnitus.

### Claim 8 (depends on 1)

The method of claim 1, wherein administration of group II mGluR agonist provides suppression of tinnitus for about 5 to about 25 minutes following administration.

### Claim 9

A method of screening a subject having tinnitus for temporary suppression of tinnitus with a group II metabotropic glutamate receptor (mGluR) agonist, comprising testing the use of residual inhibition to suppress tinnitus in the subject, wherein suppression of tinnitus by residual inhibition indicates that a group II mGluR agonist would be effective for temporarily suppressing tinnitus in the subject, further comprising administering a therapeutically effective amount of a group II mGluR agonist to a subject in which tinnitus is suppressed by residual inhibition.

### Claim 10 (depends on 9)

The method of claim 9, wherein the use of residual inhibition to suppress tinnitus in the subject is tested by administering a masking stimulus using a sound synthesizer.

### Claim 11 (depends on 9)

The method of claim 9, wherein the group II mGluR agonist is LY354740 or an LY354740 prodrug, or a pharmaceutically acceptable salt thereof.

### Claim 12 (depends on 1)

The method of claim 1, wherein administration of the group II mGluR agonist provides suppression of tinnitus for up to 2 hours following administration.

### Claim 13 (depends on 1)

The method of claim 1, wherein a dose ranging from 0.001 mg/kg to 30 mg/kg body weight of the mGluR agonist is administered to the subject.