Use of oxidase inhibitor with dextromethorphan to treat...

A - Human Necessities – 61 – K

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Details

A61K 31/49 (2006.01) A61K 31/485 (2006.01) A61P 25/28 (2006.01)

Patent

CA 2114267

This invention discloses a method for increasing the effectiveness of dextromethorphan (DM) in treating either severe coughing or dermatitis which do not respond to other drug treatments. This method involves the administration, to a patient who is an extensive metabolizer of dextromethorphan and who is suffering from severe coughing or dermatitis, of dextromethorphan along with a second agent that inhibits the enzymatic activity of debrisoquin hydroxylase (also called sparteine monooxygenase, cytochrome P450DB, and cytochrome P450-2D6). Quinidine is an especially potent inhibitor of enzymatic DM oxidation, but it is not well tolerated by everyone. Other antioxidants which are less potent and better tolerated by some patients include quinine, yohimbine, fluoxetine, haloperidol, ajmaline, lobeline, and pipamperone. Since people have major variations in their oxidative enzyme activities, screening tests should be undertaken under the supervision of a physician to select a preferred antioxidant for each particular patient. In tests described herein, patients suffering from intractable coughing or dermatitis which did not respond adequately to any other safe and non-addictive drugs reported excellent results and virtually complete elimination of their coughing or dermatitis. In addition, the treated patients did not report any adverse side effects such as drowsiness, fatigue, or nausea.

L'invention porte sur une méthode permettant d'augmenter l'efficacité du dextrométhorphane (DM) dans le traitement de la dermatite ou la toux grave chez le patient qui ne répond pas aux autres traitements médicamenteux. Cette méthode comprend l'administration de dextrométhorphane en association avec un deuxième agent qui inhibe l'activité enzymatique de la débrisoquine hydroxylase (aussi appelée spartéine monooxygénase, cytochrome P450DB et cytochrome P450-2D6), à un patient qui métabolise rapidement le dextrométhorphane et qui présente une dermatite ou une toux grave. La quinidine est un inhibiteur particulièrement puissant de l'oxydation enzymatique du DM, mais il n'est pas toujours bien toléré. Parmi les autres antioxydants moins puissants et mieux tolérés par certains patients figurent la quinine, la yohimbine, la fluoxetine, l'halopéridol, l'ajmaline, la lobéline et la pipampérone. Puisque l'activité oxydative des enzymes peut grandement varier selon la personne, on devrait faire subir au patient des analyses sous la supervision d'un médecin afin de choisir le meilleur antioxydant. Dans les analyses décrites dans l'invention, les patients atteints d'une dermatite ou d'une toux résistante au traitement qui ne répondent pas efficacement à un autre médicament sûr et ne créant pas une dépendance ont obtenu d'excellents résultats et une disparition presque complète de leur toux ou de leur dermatite. En outre, les patients traités n'ont pas déclaré d'effets indésirables comme la somnolence, la fatigue ou les nausées.

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