# US 2008/0306019 A1 · Dopamine Receptor Agonists in the Treatment and Prevention of Hiv-Induced Dementia

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- Number: US 2008/0306019 A1
- Document ID: US20080306019A1
- Status: Published application
- Kind: A1
- Application number: 11/913,519
- Filed: 2006-05-03
- Published: 2008-12-11
- Earliest claimed: 2005-05-03
- Inventors: Rosemarie M. Booze; Charles Mactutus
- Web page: https://patentgrep.com/patent/US20080306019A1

## CPC

- A61K 31/137: Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine {or methadone}
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A61P 31/18: for HIV
- 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

Provided herein is a method of protecting a neuron from dysfunction induced by an HIV neurotoxin, comprising contacting the cell with a therapeutically effective dose of a dopamine D1 receptor agonist. Also provided is a method of treating or preventing HIV-1 associated dementia (HAD) in a subject in need of such treatment or prevention, comprising administering to the subject a therapeutically effective dose of a dopamine D1 receptor agonist and estrogenic compound.

## Claims

### Claim 1

A method of protecting a neuron from dysfunction induced by an HIV neurotoxin, comprising contacting the cell with a therapeutically effective dose of a dopamine D1 receptor agonist.

### Claim 2

A method of treating or preventing HIV-1 associated dementia (HAD) in a subject in need of such treatment or prevention, comprising administering to the subject a therapeutically effective dose of a dopamine D1 receptor agonist.

### Claim 3 (depends on 1)

The method of claim 1, wherein the dopamine D1 receptor agonist is not dopamine.

### Claim 4 (depends on 1)

The method of claim 1, wherein the dopamine D1 receptor agonist does not increase HIV-1 replication.

### Claim 5 (depends on 1)

The method of claim 1, wherein the dopamine D1 receptor agonist does not bind the dopamine D2 receptor.

### Claim 6 (depends on 1)

The method of claim 1, wherein the dopamine D1 receptor agonist does not bind the dopamine D3 receptor.

### Claim 7 (depends on 1)

The method of claim 1, wherein the dopamine D1 receptor agonist does not bind the dopamine D4 receptor.

### Claim 8 (depends on 1)

The method of claim 1, wherein the dopamine D1 receptor agonist does not bind the dopamine D5 receptor.

### Claim 9 (depends on 1)

The method of claim 1, wherein the dopamine D1 receptor agonist is selected from the group consisting of Bromocriptine, Pergolide, Ropinirole, Pramipexole, Entacapone, Tolcapone, Fenoldopam, Apomorphine, Dihexadine, IPX-750, Cabergoline, A68930, SKF38393, CY208-243, SKF81297, NNC01-0012, and SCH23390.

### Claim 10 (depends on 2)

The method of claim 2, wherein the HAD in the subject is a result of HIV-1 infection in the presence of a psychostimulant.

### Claim 11 (depends on 10)

The method of claim 10, wherein the psychostimulant is cocaine or methamphetamine.

### Claim 12 (depends on 1)

The method of claim 1, further comprising contacting the cell with a therapeutic amount of an estrogen receptor agonist.

### Claim 13 (depends on 12)

The method of claim 12, wherein the estrogen receptor agonist is selected from the group consisting of 17 beta-estradiol, conjugated equine estrogens, synthetic conjugated estrogens, esterified estrogens, and testosterone.

### Claim 14 (depends on 13)

The method of claim 13, wherein the estrogen receptor agonist is administered in combination with Raloxifene or a Progestogen.

### Claim 15 (depends on 1)

The method of claim 1, further comprising contacting the cell with a therapeutic amount of a compound that decreases dopamine availability.

### Claim 16 (depends on 1)

The method of claim 1, further comprising contacting the cell with an antiretroviral compound.

### Claim 17 (depends on 16)

The method of claim 16, wherein the antiretroviral compound comprises one or more molecules selected from the group consisting of protease inhibitors [PI], nucleoside reverse transcriptase inhibitors [NRTI], and non-nucleoside reverse transcriptase inhibitors [NNRTI].

### Claim 18 (depends on 17)

The method of claim 17, wherein the PI is selected from the group consisting of Indinavir, Amprenavir, Nelfinavir, Saquinavir, Fosamprenavir, Lopinavir, Ritonavir, and Atazanavir.

### Claim 19 (depends on 17)

The method of claim 17, wherein the NRTI is selected from the group consisting of Abacavir, Stavudine, Didanosine, Lamivudine, Zidovudine, Zalcitabine, Tenofovir, and Emtricitabine.

### Claim 20 (depends on 17)

The method of claim 17, wherein the NNRTI is selected from the group consisting of Efavirenz, Nevirapine, and Delavirdine.

### Claim 21 (depends on 2)

The method of claim 2, wherein the dopamine D1 receptor agonist is not dopamine.

### Claim 22 (depends on 2)

The method of claim 2, wherein the dopamine D1 receptor agonist does not increase HIV-1 replication.

### Claim 23 (depends on 2)

The method of claim 2, wherein the dopamine D1 receptor agonist does not bind the dopamine D2 receptor.

### Claim 24 (depends on 2)

The method of claim 2, wherein the dopamine D1 receptor agonist does not bind the dopamine D3 receptor.

### Claim 25 (depends on 2)

The method of claim 2, wherein the dopamine D1 receptor agonist does not bind the dopamine D4 receptor.

### Claim 26 (depends on 2)

The method of claim 2, wherein the dopamine D1 receptor agonist does not bind the dopamine D5 receptor.

### Claim 27 (depends on 2)

The method of claim 2, wherein the dopamine D1 receptor agonist is selected from the group consisting of Bromocriptine, Pergolide, Ropinirole, Pramipexole, Entacapone, Tolcapone, Fenoldopam, Apomorphine, Dihexadine, IPX-750, Cabergoline, A68930, SKF38393, CY208-243, SKF81297, NNC01-0012, and SCH23390.

### Claim 28 (depends on 2)

The method of claim 2, further comprising administering to the subject a therapeutic amount of an estrogen receptor agonist.

### Claim 29 (depends on 28)

The method of claim 28, wherein the estrogen receptor agonist is selected from the group consisting of 17 beta-estradiol, conjugated equine estrogens, synthetic conjugated estrogens, esterified estrogens, and testosterone.

### Claim 31 (depends on 2)

The method of claim 2, further comprising administering to the subject a therapeutic amount of a compound that decreases dopamine availability.

### Claim 32 (depends on 2)

The method of claim 2, further comprising administering to the subject an antiretroviral compound.

### Claim 33 (depends on 32)

The method of claim 32, wherein the antiretroviral compound comprises one or more molecules selected from the group consisting of protease inhibitors [PI], nucleoside reverse transcriptase inhibitors [NRTI], and non-nucleoside reverse transcriptase inhibitors [NNRTI].

### Claim 34 (depends on 33)

The method of claim 33, wherein the PI is selected from the group consisting of Indinavir, Amprenavir, Nelfinavir, Saquinavir, Fosamprenavir, Lopinavir, Ritonavir, and Atazanavir.

### Claim 35 (depends on 33)

The method of claim 33, wherein the NRTI is selected from the group consisting of Abacavir, Stavudine, Didanosine, Lamivudine, Zidovudine, Zalcitabine, Tenofovir, and Emtricitabine.

### Claim 36 (depends on 33)

The method of claim 33, wherein the NNRTI is selected from the group consisting of Efavirenz, Nevirapine, and Delavirdine.

### Claim 301 (depends on 29)

The method of claim 29, wherein the estrogen receptor agonist is administered in combination with Raloxifene or a Progestogen.