Compositions and methods for increasing compliance with therapies using aldehyde dehydrogenase inhibitors and treating alcoholism

Abstract

Compositions and methods for treating, preventing, or reducing alcoholism, in particular methods for increasing patient compliance with therapies that require the intake of an ALDH inhibitor comprising the step of administering a monoamine oxidase B inhibitor.

Description

[0001] This patent application claims the benefit of the filing date of U.S. Patent Application No. 60 / 338,901 filed on Nov. 5, 2001, the entire contents of which are hereby expressly incorporated by reference.[0002] 1. Field of the Invention[0003] The present invention relates to compositions and methods for increasing patient compliance with therapies comprising the administration of aldehyde dehydrogenase inhibitors, and for preventing, ameliorating or treating alcoholism. Such compositions and methods may be used to facilitate alcohol cessation, and may comprise a combination of aldehyde dehydrogenase inhibitors and monoamine oxidase inhibitors.[0004] 2. Description of the Related Art[0005] Alcohol is a commonly abused drug. According to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), problematic alcohol use is divided into alcohol abuse and alcohol dependence.[0006] Alcohol abuse involves recurrent alcohol consumption that negatively affects one's life, wher...

AI Technical Summary

Benefits of technology

[0018] There is provided in one embodiment of the present invention compositions and methods for increasing the rate of continuous abstinence, delaying resumption of abuse or dependence and / or preventing relapses in patients being treated for alcoholism.

[0019] There is further provided a method for increasing patient compliance with therapies that require self-administration of an ALDH inhibitor comprising the step of administering a therapeutically effective amount of a MAOB inhibitor.

[0025] A prodrug of a MAOB inhibitor is a derivatized MAOB inhibitor that is metabolized in vivo into the active inhibitory agent. Prodrugs according to this invention preferably have substantially the same or better therapeutic value than the underivatized MAOB inhibitor. For example, a prodrug useful according to this invention can improve the penetration of the drug across biological membranes leading to improved drug absorption; prolong duration of the action of the drug, e.g., slow release of the parent drug from the prodrug and / or decrease first-pass metabolism of the drug; target the drug action; improve aqueous solubility and stability of the drug (e.g., intravenous preparations, eyebrows etc.); improve topical drug delivery (e.g., dermal and ocular drug delivery); improve the chemical and / or enzymatic stability of drugs (e.g., peptides); or decrease side effects due to the drug. Methods for making prodrugs are readily known in the art.

Problems solved by technology

Alcohol abuse and dependence commonly lead to other problems such as alcohol-related violence, motor vehicle accidents, and medical consequences of chronic alcohol ingestion including death [McRae et al., supra; Swift, supra].

Patients who consume such inhibitors of ALDH experience mild to severe discomfort if they ingest alcohol.

In fact, patient compliance is a significant problem with these types of therapies.

Although disulfiram has been available in the United States for many decades, patients frequently have difficulty complying with disulfiram treatment therapies.

One reason for poor compliance is the lack of motivation for the patient to continue to take disulfiram, that is, other than self-motivation (i.e., there is no positive reinforcement for taking disulfiram).

In fact, disulfiram has not proven to be useful in maintaining long-term sobriety [Kick, supra].

One of the major problems associated with therapies using ALDH inhibitors is ensuring patient compliance with the regimen.

However, WO 99 / 21540 does not suggest pharmacotherapy for ensuring patient compliance with the regimen, which is important for the success of the treatment.

However, none of the above references teach or suggest the use of MAOB inhibitors in therapies using ALDH inhibitors.

Moreover, none of these references teach that MAOB inhibitors have a sustained effect on ensuring patient compliance with other therapies.

Alcohol abuse as a maladaptive pattern of alcohol use that leads to clinically significant impairment or distress.