Methods related to opioid therapeutics
View Patent ↗The present invention provides methods for modulating opioid receptor mediated analgesic effect, e.g., promoting or enhancing analgesia in subjects in need of pain relief. Also provided in the invention are methods for ameliorating or suppressing withdrawal symptoms in subjects with chronic opioid use. These methods of the invention entail administering to the subjects in need of treatment a therapeutically effective amount of a GPR139 antagonist compound. The invention further provides methods for identifying novel compounds that can be useful for modulating opioid receptor mediated analgesic effect.
1. A method for providing or enhancing analgesic effect mediated by the μ-opioid receptor (MOR) in a subject, comprising administering to the subject a pharmaceutical composition comprising an effective amount of a compound that down-regulates expression or cellular activity of GPR139 or an ortholog thereof, wherein the compound is a small organic molecule, thereby enhancing MOR mediated analgesic effect in the subject.
2. The method of claim 1 , wherein the subject is administered with an opioid drug for pain relief.
3. The method of claim 2 , wherein the subject is administered with the opioid drug prior to, simultaneously with, or subsequent to administration of the pharmaceutical composition.
4. The method of claim 2 , wherein the opioid drug is oxycodone, hydrocodone, morphine, codeine, fentanyl, buprenorphine or methadone.
5. The method of claim 1 , wherein the subject is a human.
6. The method of claim 1 , wherein the compound down-regulates GPCR signaling activity of GPR139 or an ortholog thereof.
7. The of claim 6 , wherein the compound is selected from the following table:
Compound Identifier
Compound Structure
NCRW0001-C02
NCRW0005-F05
LP-114958
LP-471756