Title:  Use of pramipexole for the treatment of addictive disorders

United States Patent:  6,410,579

Assignee:  Pharmacia & Upjohn Company (Kalamazoo, MI)

Filed:  February 14, 2001

This patent application describes the treatment addictive disorders, psychoactive substance use disorders, intoxication disorders, inhalation disorders, alcohol addiction, tobacco addiction and or nicotine addiction comprising administering a therapeutically effective, nontoxic dose of pramipexole and derivatives and or pharmaceutically acceptable salts thereof to a patient.

SUMMARY OF THE INVENTION

The present invention particularly provides a method for the treatment of certain addictive disorders, such as pychoactive substance use disorders, nicotine addiction or tobacco addiction (with a result of smoking cessation or a decrease in smoking) comprising administering a therapeutically effective, nontoxic dose of pramipexole and derivatives and or pharmaceutically acceptable salts thereof to a patient suffering from or susceptible to such an addiction or disorder comprising the administration of an effective amount of pramipexole. By pramipexole is meant 2-amino-6-n-propylamino-4,5,6,7-tetrahydrobenzothiazole, its (-)-enantiomer thereof, or (S)-2-amino-4,5,6,7-tetrahydro-6-(propylamino)-benzothiazole and pharmacologically acceptable salts thereof especially (-)-2-amino-6-n-propylamino-4,5,6,7-tetrahydrobenzothiazole dihydrochloride (H₂ O).

2-Amino-6-n-propyl-amino-4,5,6,7-tetrahydrobenzothiazole, particularly the (-)-enantiomer thereof, and the pharmacologically acceptable acid addition salts thereof can be given for treating the addictive disorders described here. The form of conventional preparations consist essentially of an inert pharmaceutical carrier and an effective dose of the active substance; e.g., plain or coated tablets, capsules, lozenges, powders, solutions, suspensions, emulsions, syrups, suppositories, etc.

Preferred are tablets containing the following amounts of active drug, in mg/tablet: 0.125, 0.25, 0.5, 1.0, 1.25 and 1.5 mg of pramipexole base (mg pramipexole 2HCl), respectively, and further comprising mannitol, maize starch, colloidal silica, polividone and magnesium stearate as excipients. Preferred would be starting dose of 0.125 mg provided to a patient 3 times per day (tid). After accepting the starting dose, the patient may then seek to increase the dosage to a higher level with increases every 5 to 7 days up to a maximum dose of 10 mg/day, a preferred higher total daily dosage of about 6 mg/day with a more preferred highest dosage of about 4.5 to 5 mg/day.

For treating the addictive disorders described herein the drug may also be provided in chewable format, such as a chewing gum. The amount of active drug put in a chewable base may be half that suggested above, starting with about 0.075 mg per square of chewing gum being administered tid and followed with higher levels after the patient shows tolerance to the drug. Several chewing gum dosages are considered here including; 0.075, 0.10, 0.125, 0.150, in addition to those mentioned for a tablet. One or two chewing gum squares could be provided up to three times a day, depending on the therapeutic need of the patient.

Transdermal administration, such as with a skin patch application, and inhalation therapy, such as with an inhaler, is also foreseen where the patch or inhaler would deliver levels of pramipexole to the patient's blood in levels comparable to that suggested herein. A transdermal patch containing pramipexole could also be combined with a patch containing nicotine with the goal being the elimination of craving for tobacco containing products.

The drug is typically first administered to a patient at a low dosage to avoid possible nausea that may occur with higher starting doses. The dose is then titrated up to higher levels until a suitable therapeutic effect is acheived.

The effective dose range can be from 0.01 to 10.0 mg/day and patient, preferred is between 0.125 and 6 mg/day, more preferred between 0.375 to 5 mg/day and especially preferred is between 0.75 and 4.5 mg/day to a patient. In addition to being administered by oral or intravenous route pramipexole may also be administered transdermally or by inhalation.

Dosages should be typically increased gradually from a starting dose of about 0.125 mg of base drug given to the patient three times per day and then increased every 5-7 days until optimal therapeutic effect is achieved. Providing patients do not experience intolerable side effects, the dosage should be titrated to achieve a maximal therapeutic effect. One ordinarily skilled in art of providing medicine, such as a physician or pharmacist should be able to determine the optimal dosage level after considering a patients age, size, medical history, responsiveness to and toleration for the drug.

Description of the Disorders that May Be Treated With Pramipexole

Addictive disorders and psychoactive substance use disorders, such as intoxication disorders, inhalation disorders, alcohol addiction, tobacco addiction and/or nicotine addiction. Tobacco and nicotine addiction would be treated with the goal of achieving either smoking cessation or smoking reductions.

Addictive disorders, alcohol and other psychoactive substance use disorders, disorders related to intoxication and inhalants and especially tobacco addiction or nicotine addiction, may be treated with pramipexole. Tobacco addiction or nicotine addiction would be treated with pramipexole in order to achieve smoking/chewing cessation or smoking/chewing reduction. General descriptions of addictive disorders, including disorders related to intoxication and inhalants and tobacco addiction or nicotine addiction may be found in many standard sources, such as, The American Psychiatric Press Textbook of Psychiatry, Second Edition, Edited by Robert E. Hales, Stuart C. Yudofsky, and John A. Talbott, copyright 1994, incorporated by reference, especially pp. 401 et. seq., section on "Nicotine" incorporated by reference. Another of many texts is the Manual of Psychiatric Therapeutics, Second Edition, edited by Richard I. Shader, incorporated by reference, especially pp. 85 from Chapter 11 (Hypnosis).

The treatment of alcohol and other psychoactive substance use disorders, such as disorders related to intoxication and inhalants and tobacco addiction or nicotine addiction but especially tobacco addiction involves the administration of pramipexole in a manner and form that provide a reduction in the symptoms of the disease. Tobacco addiction or nicotine addiction in particular would be treated to achieve a reduction or cessation of smoking or chewing of nicotine containing materials by a patient. Cessation or a reduction in smoking or chewing of addictive or psychoactive substances involves the administration of pramipexole in a manner and form that provide a reduction in the symptoms of the disease, or with tobacco or nicotine with a reduction in the amount smoked or chewed. See the description above for methods and dosages for the proper administration of pramipexole for the treatment of these diseases and symptoms.

Claim 1 of 14 Claims

What is claimed is:

1. A method of treating or enhancing the treatment of a disorder selected from, addictive disorders, psychoactive substance use disorders, intoxication disorders, inhalation disorders, alcohol addiction, tobacco addiction and nicotine addiction comprising:

administering a therapeutically effective, nontoxic dose of a compound selected from the group consisting of pramipexole, an (-)-enantiomer of pramipexole, pramipexole dihydrochloride, pramipexole dihydrochloride-(H₂ O), and a pharmaceutically acceptable salt of any said compound to a patient, wherein said compound is administered orally or by inhalation.

____________________________________________
If you want to learn more about this patent, please go directly to the U.S. Patent and Trademark Office Web site to access the full patent.