Treatment of addiction and impulse-control disorders using PDE7 inhibitors
Inventors
Demopulos, Gregory A. • Gaitanaris, George A.
Assignees
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Publication Number
US-11207275-B2
Publication Date
2021-12-28
Expiration Date
Abstract
This disclosure is directed to treatment of addictions and primary impulse-control disorders using phosphodiesterase 7 (PDE7) inhibitors, alone or in combination with other therapeutic agents.
Core Innovation
Methods utilize a phosphodiesterase 7 (PDE7) inhibitor selected from formulas 6A through 6H to treat or reduce relapse use of addictive agents, treat relapse into addictive or compulsive behaviors, or treat or prevent addiction. One method specifically targets subjects who previously reduced or eliminated use in response to anti-addiction treatment and are no longer exposed to an effective amount of that treatment. Target agents include alcohol, nicotine, marijuana or marijuana derivatives, opioid agonists, benzodiazepines, barbiturates, and psychostimulants.
The disclosure describes structural substituent ranges, chemotypes, and specific PDE7 inhibitors, including thiazole-pyrimidine derivatives, quinazolinone derivatives, formulas 13 through 34, ASB16165, and YM-393059, alongside stereoisomers, pharmaceutically acceptable salts, solvates, prodrugs, and hydrates. Evaluated compounds include OMS182056, OMS182401, and OMS182399 across addiction and relapse paradigms. In animal models, these agents demonstrate reductions in stress- and cue-induced cocaine relapse, chronic cocaine self-administration, stress-induced binge eating, and nicotine self-administration.
Claims Coverage
The claims define three inventive features covering methods for reducing relapse use, treating relapse involving addictive agents or behaviors, and treating or preventing addiction using phosphodiesterase 7 (PDE7) inhibitors.
Reducing relapse use after anti-addiction treatment
Claim 1 covers determining that a subject previously reduced or eliminated use of an addictive agent in response to anti-addiction treatment and is no longer exposed to an effective amount of that treatment, followed by administering a selective phosphodiesterase 7 (PDE7) inhibitor selected from formulas 6A–6H to reduce relapse use after abstinence, limited use, or reduced use of alcohol, nicotine, marijuana or a marijuana derivative, an opioid agonist, a benzodiazepine, a barbiturate, or a psychostimulant.
Treating relapse involving addictive agents or behaviors
Claim 13 covers administering an effective amount of a phosphodiesterase 7 (PDE7) inhibitor selected from formulas 6A–6H to treat relapse use of the specified addictive agents, or relapse into practice of an addictive or compulsive behavior associated with a primary impulse-control disorder or obsessive-compulsive disorder, in a subject who has undergone a period of abstinence, limited use, or reduced use.
Treating or preventing addiction
Claim 14 covers determining that a subject has or is at risk of developing an addiction and administering an effective amount of a phosphodiesterase 7 (PDE7) inhibitor selected from formulas 6A–6H to treat or prevent the addiction, wherein the addiction involves the specified addictive substances or an addictive or compulsive behavior associated with a primary impulse-control disorder or obsessive-compulsive disorder.
Together, all elements of the claim define methods using phosphodiesterase 7 (PDE7) inhibitors selected from formulas 6A–6H for relapse reduction following anti-addiction treatment, relapse treatment across addictive substances and compulsive behaviors, and addiction treatment or prevention.
Stated Advantages
Phosphodiesterase 7 (PDE7) inhibition treats or reduces relapse use of specified addictive agents, treats relapse into specified addictive or compulsive behaviors, and treats or prevents addiction.
Animal studies report that phosphodiesterase 7 (PDE7) inhibitors OMS182401 and OMS182056 reduce stress- and cue-induced cocaine relapse, chronic cocaine self-administration, stress-induced binge eating, and nicotine self-administration and reinstatement, though certain cocaine self-administration and priming-relapse tests show no significant benefit.
Documented Applications
Reducing or treating relapse use of alcohol, nicotine, marijuana or a marijuana derivative, an opioid agonist, a benzodiazepine, a barbiturate, or a psychostimulant after a period of abstinence, limited use, or reduced use.
Treating relapse into an addictive or compulsive behavior associated with a primary impulse-control disorder or obsessive-compulsive disorder after a period of abstinence, limited practice, or reduced practice.
Treating or preventing addiction to the specified addictive substances or involving the specified addictive or compulsive behaviors in a subject who has or is at risk of developing an addiction.
Animal-model applications evaluating cocaine addiction and relapse, nicotine self-administration and reinstatement, and stress-induced binge eating.
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