Compounds and methods for treating addiction and related disorders
Inventors
Korinek, William S. • Liston, Theodore E • Lechleiter, James D. • Beckstead, Michael
Assignees
University of Texas System • Astrocyte Pharmaceuticals Inc
Publication Number
US-11839615-B2
Publication Date
2023-12-12
Expiration Date
2039-02-08
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Abstract
The present invention relates to adenosine receptor agonist compounds and methods of use thereof for treatment of certain disorders and conditions, for example an addiction or compulsive disorder. Exemplary compounds for use in disclosed methods include: and pharmaceutically acceptable salts thereof.
Core Innovation
The present invention concerns adenosine receptor agonist compounds and their methods of use for treating, ameliorating, or promoting recovery from diseases and disorders such as addictions, addictive behaviors, behavioral addictions, brain reward system disorders, compulsive disorders, and related conditions. The compounds include those that are selective or biased agonists or antagonists of adenosine A3 receptors or P2Y1 receptors, such as AST-004 or MRS1873 (AST-008), or their pharmaceutically acceptable salts. These methods are based on the modulation of energy metabolism in astrocytes and related cells in the brain or central nervous system.
The problem addressed is the lack of effective treatments for addictions and compulsive disorders. Addictive drugs like heroin, cocaine, alcohol, opiates, nicotine, and amphetamines act on the brain's reward system, causing persistent changes in dopamine-mediated reinforcement and leading to compulsive drug-seeking behaviors and withdrawal symptoms. Current treatments are insufficient in restoring normal brain function or preventing relapse.
The core of the innovation is the discovery and use of specific agonist compounds that, by targeting adenosine and purinergic receptors on astrocytes and other central nervous system cells, reverse addiction-associated loss of glutamate uptake and restore or enhance energy metabolism and mitochondrial ATP production. These compounds not only treat addiction and withdrawal but may also address relapse and a broad spectrum of compulsive and behavioral disorders by restoring neural function through astrocyte activation. Methods include administering these compounds in effective amounts for oral, intravenous, or parenteral use to subjects in need.
Claims Coverage
The patent claims encompass three main inventive features regarding methods of treating and promoting recovery from addiction, withdrawal, and related behavioral or compulsive disorders using specific receptor agonist compounds.
Method of treating or promoting recovery from addiction and related disorders by administering specific compounds
This inventive feature covers the administration to a subject in need of an effective amount of a compound selected from a specified list of adenosine or purinergic receptor agonists or their pharmaceutically acceptable salts. The conditions targeted include addiction, addictive behavior, behavioral addiction, brain reward system disorder, compulsive disorder, or treating relapse of an addiction or addictive behavior.
Method of treating or promoting recovery from withdrawal caused by addiction to drugs of abuse using specified compounds
This inventive feature covers the administration to a subject in need of an effective amount of a compound selected from a specified group of adenosine or purinergic receptor agonists or their pharmaceutically acceptable salts for treating or promoting recovery from withdrawal caused by addiction to substances or drugs with abuse potential.
Method of treating or promoting recovery from addictive behaviors or compulsive disorders by administering defined compounds
This inventive feature covers the administration of an effective amount of a compound from a specified list to treat or promote recovery from an addictive behavior, behavioral addiction, brain reward system disorder, compulsive disorder, or related condition, with the compounds being adenosine receptor or purinergic receptor agonists or their pharmaceutically acceptable salts.
The patent's inventive features collectively claim methods of treating addiction, withdrawal, relapse, and broad compulsive or behavioral disorders using specific adenosine or purinergic receptor agonist compounds administered in pharmaceutically acceptable forms.
Stated Advantages
Compounds selectively modulate adenosine A3 or P2Y1 receptors, allowing targeted activation of astrocytes for improved treatment and avoidance of undesired pathway modulation.
The invention provides methods that may reverse loss of glutamate uptake in astrocytes caused by addiction, thereby restoring brain function.
Disclosed compounds can increase energy metabolism and mitochondrial ATP production in astrocytes and other central nervous system cells.
Compounds of the invention show high solubility and low plasma and brain binding, resulting in higher concentrations of unbound drug available to interact with the target receptor.
The methods offer treatment not only for addiction and withdrawal, but also for preventing relapse and treating a range of compulsive and behavioral disorders.
Documented Applications
Treatment, prevention, or recovery promotion from addiction, addictive behaviors, behavioral addictions, brain reward system disorders, and compulsive disorders, including but not limited to substance and drug addiction.
Treatment or prevention of withdrawal symptoms caused by addiction to substances or drugs having abuse potential, including alcohol, nicotine, heroin, cocaine, and others listed.
Treatment or prevention of relapse in addicted individuals, including those addicted to prescription drugs and recreational drugs.
Treatment or prevention of compulsive disorders and behaviors such as OCD, Tourette syndrome, trichotillomania, anorexia, bulimia, anxiety disorder, psychosis, post-traumatic stress disorder, gambling, sex addiction, pornography addiction, eating disorders, spending addiction, rage/anger, workaholism, exercise addiction, risk-taking behaviors, perfectionism, internet or video game addiction, and compulsive use of electronic devices.
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