Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1996-12-09
1998-06-30
Jordan, Kimberly
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
514397, A61K 3155, A61K 31415
Patent
active
057734364
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/EP95/01264, filed Apr. 6, 1995.
This invention relates to a new use of 5HT.sub.3 antagonists.
These compounds are also referred to hereinafter as compounds of the invention.
5HT.sub.3 antagonists are a class of compounds which block 5HT.sub.3 receptors. Examples include compounds disclosed in Belgian patents 897117, 900425 and 901274. These compounds are described therein as being 5HT.sub.3 receptor antagonists or serotonin M receptor antagonists (serotonin M receptors have been reclassified as 5HT.sub.3 receptors).
Other classes of the compounds of the invention are known from e.g. European patent publications 13138A, 200444A, and 214772A and British Patent publication 2153821.
5HT.sub.3 antagonists from various sources have been published for a wide variety of uses, for example for the treatment of visceral pain, migraine, vascular and cluster headache, trigeminal neuralgia, arrhythmia, serotonin-induced gastro-intestinal disorders, including emesis induced by anti-cancer agents, anxiety, stress-related psychiatric disorders, depression, cognitive disorders, social withdrawal, panic attacks, agoraphobia, lung embolism, rhinitis or serotonin-induced nasal disorders, for increasing vigilance or for treating dependency induced by dependence-inducing agents. Some have been commercially introduced for the treatment of emesis.
It has now surprisingly been found that the compounds of the invention exert a marked improvement in patients suffering from fibromyalgia, which affects the major symptoms including pain as well as the functional and vegetative disorders and lasts beyond the time of treatment.
Fibromyalgia (also known as fibrositis or generalized tendomyopathy) is a very common disease which is characterized by pains and stiffness in the various regions of the locomotory apparatus, particularly in the region of the tendon insertions and tendon sheaths, which are very sensitive to pressure, furthermore by functional and vegetative disorders as well as psychopathological findings such as depressive conditions and neuroses.
Examples of functional symptoms are sleep disorders, headache, migraine, globus sensation, functional breathing and cardiac complaints, gastrointestinal disorders and dysuria. Examples of vegetative symptoms are cold extremities, hyperhidrosis, dryness of mouth, dermatographia, tremor, respiratory arrhythmia and orthostatic problems.
The treatment of fibromyalgia is very problematic and unsatisfactory. An effective therapy of the disease is not available yet. Attempts to attenuate the pain symptoms using analgesics and non-steroidal anti-inflammatories were unsuccessful. Muscle relaxants showed limited activity at very high dosages which induced considerable side effects and had to be stopped. Antidepressive drugs such as amitriptyline were also proposed and showed some activity in a sub-group of patients, which however decreased rapidly.
The compounds of the invention include compounds of formula I ##STR2## wherein R.sub.1 is hydrogen, halogen, hydroxy, alkoxy(1-4C), amino, alkyl(1-4C)amino or dialkyl (1-4C)amino, cycloalkyl(3-7C), cycloalkyl(3-7C)alkyl(1-4C), phenyl, phenylalkyl(1-3C), alkyl(1-6C)carbonyl, alkyl(1-6C)oxycarbonyl, carbamoyl, sulfamoyl or mono- or dialkyl(1-6C)-carbamoyl or -sulfamoyl, -(CH.sub.2).sub.m -, m being 2 or 3, ##STR3## wherein o is 0, p is 0, 1 or 2 and q is 0, 1 or 2, or o is 1, p is 0 and q is 0 or 1, and optionally mono- or disubstituted by halogen, alkyl(1-4C) or alkoxy(1-4C), ##STR4## wherein o' is 1, 2 or 3, p' is 0 or 1 and q' is 0 or 1, or a radical of formula (c) or (d) ##STR5## wherein one of R.sub.5, R.sub.6 and R.sub.7 is hydrogen, alkyl(1-6C), cycloalkyl(3-7C), alkenyl(2-6C), phenyl or phenylalkyl(1-3C) and the 2 others independently are hydrogen or alkyl(1-6C), provided that Z is not (d) when n is 0 and Y is NR.sub.3 or (with X) N-A-C,
R.sub.1 is preferably hydrogen or methoxy.
R.sub.2 is preferably hydrogen or alkyl(1-7C).
In R.sub.2, alkyl(1-7C) is preferably alkyl(1-4C), more preferably methyl, alkenyl(3-6C) i
REFERENCES:
Zeitschrift fur Rheumatologie, vol. 55, No. 6, pp. 335-338 (1994).
Rheumatologia, vol. 32, No. 4, pp. 404-408 (1994).
Br. J. Rheum., vol. 34, No. 3, pp. 283-284 (1995).
Muller Wolfgang
Stratz Thomas
Borovian Joseph J.
Jordan Kimberly
Novartis AG
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