MXPA00009883A - New treatments for nervous disorders - Google Patents

Abstract

This patent application describes the treatment of Addictive disorders, Psychoactive Substance Use disorders, Intoxication disorders, Inhalation disorders, Alcohol addiction, Tobacco addiction and or Nicotine addiction;and Attention Deficit Hyperactivity Disorder (ADHD);comprising administering a therapeutically effective, nontoxic dose of Reboxetine and derivatives and or pharmaceutically acceptable salts thereof to a patient.

Description

NOVEDOS TREATMENTS FOR NERVOUS DISORDERS FIELD OF THE INVENTION This invention describes novel treatments for various nervous disorders, among which are: Addictive Disorders, Disorders by Use of Psychoactive Substances, Nicotine Addiction or Acupuncture Tobacco that results in a cessation of the habit of Smoking and Hyperactivity Disorder with Attention Deficit.

BACKGROUND OF THE INVENTION The introduction of tricyclic antidepressants in the early 1960s has provided an important advance in the treatment of neuropsychiatric disorders. Diagnostics of reactive and endogenous depressions, which previously had serious prognostic implications, with the introduction of tricyclics have become manageable disorders at a much lower cost to the patient and to society in general. Electroconvulsive shock therapy, which was a long time ago. Unique effective treatment despite its extremely invasive nature, thanks to tricyclics is now an obsolete form of treatment in most countries. The first tricyclic compounds were reuptake inhibitors of all the catecholamines released in the synaptic cleft, resulting in the prolongation and intensification of the action of dopamine (DA), noradrenaline (NA) and serotonin (5-hydroxytryptamine = 5-HT) . Desipramine, for example, has been characterized as "one of the most studied tricyclic antidepressants in children and adolescents with ADHD". TEA. Wilens, et al., Am. J. "Psychiatry 153: 1147-1153, 1148 (1996) .It has also been considered as a treatment for the disease in adults." Unfortunately, the lack of selectivity in most tricyclics. , including desipramine, may also cause undesirable side effects, particularly in acetylcholine-mediated neurotransmission (especially the muscarinic component) and histamine. Due to these undesirable pharmacodynamic activities, cognitive damage, sedation, alterations of the urinary tract and gastrointestinal tract and increased intraocular pressure were limiting factors in the clinical use of these compounds and often required the suspension of treatment. The toxic cardiac effects and the proconvulsive activity of this group of drugs were also of great concern. It is also known that another drug, methylphenidate, has clinical efficacy in the treatment of ADHD. Wender, P.H., et al., Am. J. Psychiatry 142: 547-552 (1985). In more recent years, selective serotonin reuptake inhibitors (SSRIs) have been introduced with definite advantages in terms of fewer side effects and no loss of efficacy. We present here the surprising finding that a particular drug, of a new category of antidepressants, the so-called noradrenaline reuptake inhibitor (NA), can be used to manage or treat some special diseases, diseases that have symptoms other than those that have been considered in general the symptoms of depression. Now these diseases can be treated with Reboxetine.

SUMMARY OF THE INVENTION This patent application describes the treatment of addictive disorders, disorders due to the use of psychoactive substances, nicotine addiction or tobacco addiction (with the consequence of smoking cessation or smoking cessation) and hyperactivity disorder with attention deficit disorder (ADHD), which comprises administering to a patient a non-toxic, therapeutically effective dose of reboxetine and derivatives and / or pharmaceutically acceptable salts thereof. Reboxetine is the generic name of the pharmaceutical substance with the chemical name 2- (a - ((2-ethoxyphenoxy) benzyl) -morpholine and its pharmaceutically acceptable salts Reboxetine may be a free base or may include reboxetine methanesulfonate (referred to as also reboxetine mesylate) or any other pharmaceutically acceptable salt that does not significantly affect the pharmaceutical activity of the substance A preferred dose range is between 4 and 10 mg per patient per day and the most preferred dose is between 6 and 8 mg 8 and 10 mg daily per patient, depending on the patient, is administered twice a day.

ADDITIONAL DESCRIPTION OF THE INVENTION AND PREFERRED EMBODIMENTS Reboxetine is LAS generic name of the pharmaceutical substance with the chemical name 2- (a -. ((2-ethoxyphenoxy) benzyl) -morpholine, and its pharmaceutically acceptable salts Reboxetine can be a base free or may include methanesulfonate reboxetine (also called reboxetine mesylate) or any other pharmaceutically acceptable salt that does not significantly affect the pharmaceutical activity of the substance. reboxetine and a method of synthesis are described in Patent US 4,229,449, issued October 21, 1980 to Melloni et al., Which is considered part of the present, as a reference, methods of preparation are described in United States Patent 5,068,433, issued November 26, 1991, to Melloni et al., and in U.S. Patent 5,391,735, issued February 21, 1995, which are considered foxman part of the present e, as a reference. Reboxetine also known under the tradename EDRONAX ". Pharmaceutical compositions and administration methods are described in Patent US 4229449 column 18, lines 33 to 66 and specifically considered part of the present, reference. with current formulations one dose twice a day is preferred. reboxetine acts as an antidepressant. usually antidepressants are grouped into categories or "generations." the first generation of antidepressants in general was tricyclic antidepressants such as maprotiline, affecting several neurotransmitter systems and are associated with many undesirable side effects. the second generation of antidepressants, such as mianserine, mirtrazpina and trazodone are largely devoid of anticholinergic action and their adrenolytic and antihistaminic effects are weaker. This contrasts with the third generation of antidepressants ( for example, SSRIs, isapirone, viloxazine, reboxetine, bupropion) that mediate only one of the three systems of the major neurotransmitters of depression (5-HT, noradrenaline, dopamine) and do not affect the brain systems of muscarine, histamine and adrenergic. Svestka, J. "Antidepressants of the 3rd, 4th and 5th generation", Cesk-Psychiatr. 1994 Feb; 90 (1): 3-19 (Czech). However, reboxetine does not act like most antidepressants. Unlike tricyclic antidepressants and even selective serotonin reuptake inhibitors (SSRIs), reboxetine is ineffective in the hypothermia test 8-OH-DPAT, indicating that reboxetine is not a selective inhibitor of serotonin reuptake , rather it is selective for the noradrenergic system. In this way, reboxetine is not an SSRI, rather it is considered a novel selective norepinephrine reuptake inhibitor (NRTI). Leonard-BE, "Noradrenaline in basic models of depression", European-Neuropsychopharmacol. , 1997 Apr; 7 Suppl. l: Sll-6; discussion S71-3. Unlike most drugs, reboxetine is a selective selective norepinephrine reuptake inhibitor, only with marginal serotonin reuptake inhibitory activity and not dopamine. The compound shows only weak or no anticholinergic activity in different animal models and has no inhibitory activity of monoamine oxidase (MAO). Reboxetine is very powerful and fast acting. Our research indicates that reboxetine has a potent antiresermin activity and combines the inhibitory properties of classical tricyclic antidepressants in the reuptake of noradrenaline with an ability to desensitize ß-adrenergic receptor function without showing any appreciable interaction with cholinergic receptors and a- adrenergic In addition, reboxetine shows less vagolytic activity than other tricyclic antidepressants. The inventors have discovered that due to their unique properties, reboxetine is considered particularly useful for treating or reinforcing the treatment of psychiatric symptoms or disorders, with greater efficacy and with fewer side effects than when treated by known drugs. In addition, the inventors have also discovered that reboxetine can be used to treat or reinforce the treatment of some other specific psychiatric symptoms or disorders. Symptoms or disorders amenable to treatment with reboxetine are described below. The dosage used to treat all disorders described herein is as follows. Reboxetine is well tolerated and has a wide range of safety, it can be administered in a dose range of active ingredient of approximately between 1 and more 20 mg / kg. The most common is that it is administered in doses of 1 to 20 mg per patient per day. The compound can be administered by any appropriate method, including a suitable oral dosage form. One preferred method is oral dosing twice a day. The preferred dose range is between 4 and 10 mg 'per patient per day and the most preferred dose is between 6 and 8 mg or 8 and 10 mg daily per patient, depending on the patient, it is administered twice a day. It can also be administered in dosages of 2, 4, 6, 8, 10 or 12 mg per patient per day or fractions thereof. For example, adequate administrations could be 4 mg in the morning and 2 or 4 mg in the afternoon or 6 mg in the morning and 4 mg in the afternoon. In some patients the ideal dosage could be 3 to 5 mg in the morning and 3 to 5 mg in the afternoon. A skilled physician would be expected to determine the precise dosage level. The ideal dosage could be determined routinely by an evaluation of clinical trials and the needs of the patient. The diseases described here for treatment are: I. Addictive disorders, disorders due to the use of psychoactive substances such as intoxication disorders, inhalation disorders, alcohol addiction, tobacco addiction or nicotine addiction. Addiction to tobacco or nicotine would be treated with the aim of achieving either cessation in smoking or reduction of smoking. Addictive disorders, disorders by the use of alcohol and other psychoactive substances, disorders related to poisoning and inhalants and especially addiction to tobacco or nicotine can be treated with reboxetine. Addiction to tobacco or nicotine addiction could be treated with reboxetine in order to achieve cessation of smoking or chewing or reduction in smoking or chewing. General descriptions of addictive disorders, which include disorders related to intoxication and addiction to inhalants or tobacco and nicotine addiction, can be found in many commonly used sources, for example, The American Psychiatric Press Textbook of Psychiatry , Second Edition, edited by Robert E. Hales, Stuart C. Yudofsky and John A. Talbott, copyright 1994, which is considered part of this, as a reference, especially, the section on "Nicotine" p. 401 and following. Another of the many texts is the Manual of Psychiatric Therapeutics, Second Edition, edited by Richard I. Shader, which is considered part of this, as a reference, especially p. 85 of Chapter 11 (Hypnosis), considered part of this, as a reference. The treatment of disorders by the use of alcohol and other psychoactive substances, for example, disorders related to poisoning and inhalants and addiction to tobacco or nicotine, but especially tobacco addiction, involves the administration of reboxetine in one way and way that provides a reduction in the symptoms of the disease. In particular, tobacco addiction or nicotine addiction could be treated to achieve in a patient a reduction or cessation in the habit of smoking or chewing nicotine-containing materials. The cessation or reduction in the habit of smoking or chewing addictive or psychoactive substances, involves the administration of reboxetine in a manner and manner that provides a reduction in the symptoms of the disease or with respect to tobacco or nicotine, a reduction in the amount that is smoked or chewed. See the above general description for the administration of reboxetine. II. Hyperactivity Disorder due to Attention Deficit (ADHD). ADHD is a condition or disease that can be treated with reboxetine. The general descriptions of ADHD can be found in many commonly used sources, for example, The American Psychiatric Press Textbook of Psychiatry, Second Edition, edited by Robert E. Hales, Stuart C. Yudofsky and John A. Talbott, copyright 1994, which is considered part of this, as a reference, in particular, the section "ADHD" p. 741 and following. Another of the many texts is the Manual of Psychiatric Therapeutics, Second Edition, edited by Richard I. Shader, which is considered part of this, as reference, especially chapter 18, Attention-Deficit Hyperactivity Disorder and p. 172 et seq., Considered part of this, as a reference. The treatment of attention deficit hyperactivity disorder in children and adults involves the administration of reboxetine in a manner and manner that provides a reduction in the symptoms of the disease. A child or a young adult may require a lower dose depending on the size, age and condition of the patient. See previous overview for the administration of reboxetine.

Claims (10)

1. CLAIMS; 1.
2. A method for treating or reinforcing the treatment of a disorder selected from: a) "Addictive disorders, disorders by the use of psychoactive substances, intoxication disorders, inhalation disorders, alcohol addiction, tobacco addiction and / or addiction to nicotine, and b) attention deficit hyperactivity disorder (ADHD), where the method comprises administering to a patient, a non-toxic, therapeutically effective dose of reboxetine and derivatives and / or pharmaceutically acceptable salts thereof. according to claim 1, wherein the reboxetine is used to treat or reinforce the treatment of tobacco and / or nicotine addiction 3.
3. The method according to claim 2, wherein the reboxetine is used to reduce the intense desire for products that they contain tobacco or nicotine 4.
4. The method according to claim 2, wherein the reboxetine is used to reduce the habit of smoking or chewing products containing tobacco or nicotine.
5. The method according to claim 1, wherein the reboxetine is used to treat or reinforce the treatment of attention deficit hyperactivity disorder (ADHD).
6. The method according to claim 5, wherein the reboxetine is used to increase the period of attention and calm in individuals suffering from ADHD.
7. 7. A method for treating or reinforcing the treatment of a disorder selected from: a) addictive disorders, disorders by the use of psychoactive substances, intoxication disorders, inhalation disorders, alcohol addiction, addiction to tobacco and / or nicotine addiction; and b) attention deficit hyperactivity disorder (ADHD); wherein the method comprises administering a non-toxic, therapeutically effective dose of reboxetine and derivatives and / or pharmaceutically acceptable salts thereof, to a patient in need of effective treatment against said disorders.
8. 8. The use of reboxetine or its pharmaceutically acceptable salts in the manufacture of a medicament for treating: a) addictive disorders, disorders due to the use of psychoactive substances, intoxication disorders, inhalation disorders, alcohol addiction, addiction to tobacco and / or nicotine addiction; and b) attention deficit hyperactivity disorder (ADHD); The method or use according to claims 1 to 8, wherein the dose range of reboxetine is from 4 to 10 mg per patient per day. The method or use according to claims 1 to 8, wherein the dose range of reboxetine is from 6 to 8 mg per patient per day.