Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1996-09-19
1999-01-26
Spivack, Phyllis G.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514305, 514491, 514649, 514651, 514652, 514654, A61K 3144, A61K 31265, A61K 31135
Patent
active
058639276
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/US94/10771, filed Sep. 22, 1994.
BACKGROUND OF THE INVENTION
This invention relates to pharmacology. More specifically, the invention relates to compositions of matter useful for preparing medicaments for the treatment of various disorders.
A number of chronic disorders have symptoms which are known to be very difficult to treat, and often fail to respond to safe, non-addictive, and non-steroid medications. Such disorders, such as intractable coughing, fail to respond to conventional medicines and must be treated by such drugs as codeine, morphine, or the anti-inflammatory steroid prednisone. These drugs are unacceptable for long-term treatment due to dangerous side-effects, long-term risks to the patient's health, or the danger of addiction. Other disorders, such as dermatitis, have no satisfactory treatment for the severe itching and rash at this time. Drugs such as prednisone and even tricyclic antidepressants, as well as topical applications, have been tried, but do not appear to offer substantial and consistent relief.
Chronic pain due to conditions such as stroke, cancer, trauma, as well as neuropathic pain resulting from conditions such as diabetes and shingles (herpes zoster), for example, is also a problem which resists treatment. Chronic pain is estimated to affect millions of people. A variety of therapies for this type of pain have been tried, but there remains a need for safe and effective treatments.
The compound dextromethorphan, or (+)-3-methoxy-N-methylmorphinan, has been used as a cough suppressant ingredient in cough syrups. Dextromethorphan has also been tested as a potential therapeutic agent for stroke, and progressive neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis. However, the effectiveness of dextromethorphan for the treatment of any disorder has been limited because it is rapidly broken down by the liver and excreted in most individuals.
It is an object of the present invention to provide a combination of compounds useful for the preparation of medicaments which will effectively treat formerly intractable conditions not responsive to other medications. It is also an object of the present invention to provide medicaments which are safe, non-addictive, and relatively free of side-effects for patients suffering from long-term intractable conditions.
SUMMARY OF THE INVENTION
The present invention provides compounds which are useful in the preparation of medicaments for the treatment of a variety of disorders including intractable coughing, dermatitis, chronic pain, tinnitus and sexual dysfunction. These compounds are a therapeutically effective dosage of dextromethorphan and a therapeutically effective dosage of a second agent, an inhibitor of enzymatic dextromethorphan oxidation. This combination of compounds can be administered together, or individually. A preferred combination is dextromethorphan and the oxidative inhibitor quinidine. Inhibitors which may also be used include quinine, yohimbine, fluoxetine, haloperidol, ajmaline, lobeline, and pipamperone.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 shows the relationship between DM oral dosages and DM plasma concentrations in patients receiving 150 mg/day of quinidine orally.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
As used herein the term dextromethorphan (hereinafter, DM) refers to (+)-3-methoxy-N-methylmorphinan, or therapeutically effective salts and analogs thereof.
As used herein the term "antioxidants" or "oxidative inhibitors" refers to inhibitors capable of inhibiting the oxidation of DM by the liver enzyme debrisoquin hydroxylase.
As used herein, the term "intractable" or "refractory" coughing refers to coughing that will not respond adequately to non-addictive, non-steroid medications.
As used herein, the term "dermatitis" or "eczema" refers to a skin condition which includes visible skin lesions which may be accompanied by an itching or burning sensation on the skin. This condition does not readily respond
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Licht Jonathan M.
Smith Richard Alan
Bellas Christine M.
Center for Neurologic Study
Kelly Patrick D.
Spivack Phyllis G.
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