MXPA00010025A - New treatments for nervous disorders - Google Patents
New treatments for nervous disordersInfo
- Publication number
- MXPA00010025A MXPA00010025A MXPA/A/2000/010025A MXPA00010025A MXPA00010025A MX PA00010025 A MXPA00010025 A MX PA00010025A MX PA00010025 A MXPA00010025 A MX PA00010025A MX PA00010025 A MXPA00010025 A MX PA00010025A
- Authority
- MX
- Mexico
- Prior art keywords
- reboxetine
- treatment
- disorders
- ocd
- obsessive
- Prior art date
Links
- 201000010099 disease Diseases 0.000 title claims description 15
- 229960003770 reboxetine Drugs 0.000 claims abstract description 46
- 201000008430 obsessive-compulsive disease Diseases 0.000 claims abstract description 22
- 206010033666 Panic disease Diseases 0.000 claims abstract description 18
- 150000003839 salts Chemical class 0.000 claims abstract description 8
- 239000011780 sodium chloride Substances 0.000 claims abstract description 8
- 230000003000 nontoxic Effects 0.000 claims abstract description 3
- 231100000252 nontoxic Toxicity 0.000 claims abstract description 3
- CBQGYUDMJHNJBX-RTBURBONSA-N Reboxetine Chemical compound CCOC1=CC=CC=C1O[C@H](C=1C=CC=CC=1)[C@@H]1OCCNC1 CBQGYUDMJHNJBX-RTBURBONSA-N 0.000 claims abstract 8
- 239000003814 drug Substances 0.000 claims description 10
- 239000000203 mixture Substances 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims description 2
- 230000003014 reinforcing Effects 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 1
- CBQGYUDMJHNJBX-OALUTQOASA-N Esreboxetine Chemical compound CCOC1=CC=CC=C1O[C@@H](C=1C=CC=CC=1)[C@H]1OCCNC1 CBQGYUDMJHNJBX-OALUTQOASA-N 0.000 description 40
- 230000001430 anti-depressive Effects 0.000 description 8
- 239000000935 antidepressant agent Substances 0.000 description 8
- 229940005513 ANTIDEPRESSANTS Drugs 0.000 description 7
- 230000035492 administration Effects 0.000 description 7
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 6
- 229960002748 Norepinephrine Drugs 0.000 description 6
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 6
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 6
- 239000003772 serotonin uptake inhibitor Substances 0.000 description 6
- 229940053479 Selective serotonin reuptake inhibitors Drugs 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- 239000003029 tricyclic antidepressant agent Substances 0.000 description 5
- 206010057666 Anxiety disease Diseases 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 229940079593 drugs Drugs 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000002767 noradrenalin uptake inhibitor Substances 0.000 description 4
- 239000000902 placebo Substances 0.000 description 4
- 229940068196 placebo Drugs 0.000 description 4
- 231100000486 side effect Toxicity 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 230000001225 therapeutic Effects 0.000 description 4
- 206010002855 Anxiety Diseases 0.000 description 3
- 229960003638 dopamine Drugs 0.000 description 3
- -1 (2-ethoxyphenoxy) benzyl Chemical group 0.000 description 2
- 102000010909 EC 1.4.3.4 Human genes 0.000 description 2
- 108010062431 EC 1.4.3.4 Proteins 0.000 description 2
- 206010033664 Panic attack Diseases 0.000 description 2
- 206010037175 Psychiatric disease Diseases 0.000 description 2
- 230000001800 adrenalinergic Effects 0.000 description 2
- 230000001078 anti-cholinergic Effects 0.000 description 2
- 230000036506 anxiety Effects 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate Chemical compound CS([O-])(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 2
- 239000002858 neurotransmitter agent Substances 0.000 description 2
- 229960003269 reboxetine mesylate Drugs 0.000 description 2
- 230000000697 serotonin reuptake Effects 0.000 description 2
- USDUGJXCPKBJTN-UHFFFAOYSA-N 1,1-dioxo-2-[4-(4-pyrimidin-2-ylpiperazin-1-yl)butyl]-1,2-benzothiazol-3-one;hydrochloride Chemical compound Cl.O=S1(=O)C2=CC=CC=C2C(=O)N1CCCCN(CC1)CCN1C1=NC=CC=N1 USDUGJXCPKBJTN-UHFFFAOYSA-N 0.000 description 1
- ASXGJMSKWNBENU-UHFFFAOYSA-N 8-OH-DPAT Chemical compound C1=CC(O)=C2CC(N(CCC)CCC)CCC2=C1 ASXGJMSKWNBENU-UHFFFAOYSA-N 0.000 description 1
- 229960004373 Acetylcholine Drugs 0.000 description 1
- 208000008811 Agoraphobia Diseases 0.000 description 1
- 206010002758 Anticipatory anxiety Diseases 0.000 description 1
- 210000004556 Brain Anatomy 0.000 description 1
- 229960001058 Bupropion Drugs 0.000 description 1
- SNPPWIUOZRMYNY-UHFFFAOYSA-N Bupropion Chemical compound CC(C)(C)NC(C)C(=O)C1=CC=CC(Cl)=C1 SNPPWIUOZRMYNY-UHFFFAOYSA-N 0.000 description 1
- 108010009685 Cholinergic Receptors Proteins 0.000 description 1
- 206010012378 Depression Diseases 0.000 description 1
- HCYAFALTSJYZDH-UHFFFAOYSA-N Desimpramine Chemical compound C1CC2=CC=CC=C2N(CCCNC)C2=CC=CC=C21 HCYAFALTSJYZDH-UHFFFAOYSA-N 0.000 description 1
- 210000001035 Gastrointestinal Tract Anatomy 0.000 description 1
- 206010021113 Hypothermia Diseases 0.000 description 1
- 206010057840 Major depression Diseases 0.000 description 1
- QSLMDECMDJKHMQ-GSXCWMCISA-N Maprotiline Chemical compound C12=CC=CC=C2[C@@]2(CCCNC)C3=CC=CC=C3[C@@H]1CC2 QSLMDECMDJKHMQ-GSXCWMCISA-N 0.000 description 1
- 229960003955 Mianserin Drugs 0.000 description 1
- 206010029897 Obsessive thoughts Diseases 0.000 description 1
- 206010037180 Psychiatric symptom Diseases 0.000 description 1
- 206010039897 Sedation Diseases 0.000 description 1
- 229940076279 Serotonin Drugs 0.000 description 1
- UEQUQVLFIPOEMF-UHFFFAOYSA-N Tolvon Chemical compound C1C2=CC=CC=C2N2CCN(C)CC2C2=CC=CC=C21 UEQUQVLFIPOEMF-UHFFFAOYSA-N 0.000 description 1
- 229960003991 Trazodone Drugs 0.000 description 1
- PHLBKPHSAVXXEF-UHFFFAOYSA-N Trazodone Chemical compound ClC1=CC=CC(N2CCN(CCCN3C(N4C=CC=CC4=N3)=O)CC2)=C1 PHLBKPHSAVXXEF-UHFFFAOYSA-N 0.000 description 1
- 210000001635 Urinary Tract Anatomy 0.000 description 1
- 229960001255 Viloxazine Drugs 0.000 description 1
- YWPHCCPCQOJSGZ-UHFFFAOYSA-N Viloxazine Chemical compound CCOC1=CC=CC=C1OCC1OCCNC1 YWPHCCPCQOJSGZ-UHFFFAOYSA-N 0.000 description 1
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 1
- 102000034433 acetylcholine receptors Human genes 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000002908 adrenolytic Effects 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000001387 anti-histamine Effects 0.000 description 1
- 230000000891 anti-reserpine Effects 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 102000012740 beta Adrenergic Receptors Human genes 0.000 description 1
- 108010079452 beta Adrenergic Receptors Proteins 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 150000003943 catecholamines Chemical class 0.000 description 1
- 230000001149 cognitive Effects 0.000 description 1
- 229960003914 desipramine Drugs 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 201000003104 endogenous depression Diseases 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- 230000000742 histaminergic Effects 0.000 description 1
- 230000002631 hypothermal Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000004410 intraocular pressure Effects 0.000 description 1
- 230000004301 light adaptation Effects 0.000 description 1
- 229960004090 maprotiline Drugs 0.000 description 1
- 230000001404 mediated Effects 0.000 description 1
- 230000002635 muscarinergic Effects 0.000 description 1
- 230000003551 muscarinic Effects 0.000 description 1
- 201000006487 neurotic disease Diseases 0.000 description 1
- 230000002474 noradrenergic Effects 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 230000003285 pharmacodynamic Effects 0.000 description 1
- 230000003389 potentiating Effects 0.000 description 1
- 230000000216 proconvulsive Effects 0.000 description 1
- 230000036280 sedation Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000000946 synaptic Effects 0.000 description 1
- 230000005062 synaptic transmission Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing Effects 0.000 description 1
- 230000002588 toxic Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000000980 vagolytic Effects 0.000 description 1
Abstract
This patent application describes the treatment of Obsessive Compulsive Disorders (OCD), and Panic Disorder (PD), 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, which include: Obsessive-Compulsive Disorder and Disorders of
Panic. The treatment involves the administration of reboxetine.
BACKGROUND OF THE INVENTION The introduction of tricyclic antidepressants at the beginning of the 1960s has provided an important advance in the treatment of neuropsychiatric disorders. Diagnoses 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. The first tricyclic compounds were inhibitors of reuptake 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). The lack of selectivity in most tricyclics, including desipramine, can 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. 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.
SUMMARY OF THE INVENTION This patent application describes the treatment of Obsessive-Compulsive Disorder (OCD) and Panic Disorders (PD) and consists of administering to a patient a non-toxic, therapeutically effective dose of reboxetine and derivatives and / or pharmaceutically salts acceptable of it. 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 or 8 to 10 mg daily per patient, depending on the patient, administered twice a day (bid).
ADDITIONAL DESCRIPTION OF THE INVENTION AND THE PREFERRED MODALITIES 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 can be a base free or may include reboxetine methanesulfonate (also called reboxetine mesylate) or any other salt
Pharmaceutically acceptable P1119 that does not significantly affect the pharmaceutical activity of the substance. Reboxetine and a method of synthesis are described in U.S. Patent 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 disclosed in U.S. 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 part of the present, as a reference. Reboxetine is also known under the trade name EDRONAXMR. The pharmaceutical compositions and methods of administration are described in U.S. Patent 4,229,449 in column 18, lines 33 to 66 and are specifically considered to be part of the present, for reference. With current formulations, a twice-daily dose is preferred. Reboxetine acts as an antidepressant. Antidepressants are usually grouped into categories or "generations." The first generation of antidepressants in general was of tricyclic antidepressants such as maprotiline, which affect several neurotransmitter systems and are associated with many undesirable side effects. The second generation of antidepressants, as
P1119 mianserin, mirtrazpine 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 they 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, which indicates 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 the
In most of the drugs, reboxetine is a selective selective norepinephrine reuptake inhibitor, only with marginal serotonin reuptake inhibitory activity and not dopamine. The compound shows only weak anticholinergic activity or no activity, in different animal models, and has no inhibitory activity of the monoamine oxidase (MAO). Reboxetine is very powerful and fast acting. Our investigations indicate that reboxetine has a potent antireserpine 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, more effectively 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 symptoms
P111.9 or specific psychiatric 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 than 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. 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 a
P1119 evaluation of clinical tests and patient needs. The diseases described here for treatment are:
I. Obsessive-Compulsive Disorders (OCD) Obsessive-compulsive disorder is a condition or state of anxiety that can be treated with reboxetine. The general descriptions of OCD 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 chapter on "Anxiety Disorders", considered part of this as a reference. 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 chapter 5, Obsessions and Co pulsions, in particular, Section III of that chapter, "OCD" pp. 36 and following, considered part of this, as a reference. The treatment of obsessive-compulsive disorder (OCD) involves the administration of reboxetine in a manner and manner that provides a reduction in the symptoms of the disease. See previous overview for the administration of reboxetine. The following study shows the therapeutic efficacy of the use of reboxetine in doses ranging from 6 to 8 mg to treat OCD. This study is presented to illustrate the utility of using reboxetine as a treatment for OCD and the invention described herein should not be considered limited by this example. In a trial involving 10 patients diagnosed with DSM-III-R of obsessive-compulsive disorder, all were treated with reboxetine for a period of 3 to 4 weeks with a dose in the first week of 6 mg (4 mg in the morning and 2 mg at night) and in the second week an increased dose to 8 mg (4 mg twice a day). In the last CGI evaluation, 1 patient was evaluated with considerable improvement, 4 were evaluated as highly improved, 2 with minimal improvement, while 3 remained unchanged. The patients who responded had a decrease in obsessive-compulsive symptoms, as determined by the CPRS-OC qualification scale, of more than 30 and up to 73%.
II. Panic Disorder (PD) Panic disorder is a condition or state of anxiety that can be treated with reboxetine. General descriptions of PD 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 chapter on "Anxiety Disorders", considered part of this as a reference, 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 chapter 25, "Approaches to the Treatment of Anxiety
States ", considered part of this, as reference.The treatment of panic disorder involves the administration of reboxetine in a manner and manner that provides a reduction in the symptoms of the disease.See previous overview for the administration of reboxetine. The following study shows the therapeutic efficacy of the use of reboxetine in doses ranging from 6 to 8 mg to treat panic disorder.This study is presented to illustrate the utility of using reboxetine as a treatment for PD and the invention described in the present should not be considered limited by this example, in a test involving 75 patients who met the DSM-III criteria for the diagnosis of panic disorder with or without Agoraphobia (300.01, 300.21) and had at least 4 panic attacks in the month before admission, in a randomized, placebo-controlled, double-blind design group, 37 with reboxetine and 38 with placebo, the mean number of major panic attacks in patients treated with reboxetine was significantly lower than for those who were treated with placebo. All phobic symptoms, anticipatory anxiety, occupational functioning, social and family adaptation, were better at some point in time for patients treated with reboxetine than for those who were treated with placebo.
P1119
Claims (7)
- CLAIMS; 1. A method for treating or reinforcing the treatment of a disorder selected from: a) obsessive-compulsive disorders (OCD) and / or b) panic disorder (PD); wherein the method comprises administering a non-toxic, therapeutically effective dose of reboxetine and derivatives and / or pharmaceutically acceptable salts thereof, to a patient suffering from the symptoms of those disorders. The method according to claim 1, wherein the reboxetine is used to treat or reinforce the treatment of obsessive-compulsive disorders (OCD). 3. The method according to claim 1, wherein the reboxetine is used to treat or reinforce the treatment of panic disorder (PD). 4. The preparation of a medicament for treating TOC or TP, from a composition comprising reboxetine. 5. The use of reboxetine or its pharmaceutically acceptable salts, in the manufacture of a medicament for treating obsessive-compulsive disorders (OCD) and / or panic disorder (PD); and / or for the treatment of any of the symptoms of each of these diseases. 6. The method or use of claims 1 to 5, wherein the dose range of reboxetine is between 4 and 10 mg per patient per day. The method or use of claims 1 to 5, wherein the dose range of reboxetine is between 6 and 8 mg per patient per day. P1119
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
MIMI98A000870 | 1998-04-23 | ||
US60/081,632 | 1998-05-11 | ||
US60/085,033 | 1998-05-11 |
Publications (1)
Publication Number | Publication Date |
---|---|
MXPA00010025A true MXPA00010025A (en) | 2002-03-26 |
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