Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1995-02-06
1997-12-02
Fay, Zohreh
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514414, 514913, A61K 31445, A61K 3140
Patent
active
056936540
DESCRIPTION:
BRIEF SUMMARY
This invention relates to a new medical use for compounds having selective agonist activity at 5-HT.sub.1 -like receptors and to pharmaceutical compositions containing them. In particular it relates to a new medical and physiologically acceptable salts and solvates thereof.
5-HT.sub.1 -like receptors are located, for example, in the dog saphenous vein and the 5-HT.sub.1 -like receptor agonists with which the present invention is concerned contract the dog saphenous vein. Such compounds may therefore be identified by their contractile effect on the dog isolated saphenous vein strip as described, for example, by Apperley et al., Br. J. Pharmacol, 68, 215-224 (1980). Compounds which are selective 5-HT.sub.1 -like receptor agonists have also been found to selectively constrict the carotid arterial bed of the anaesthetised dog.
A variety of compounds which selectively constrict the dog isolated saphenous vein strip and which constrict the carotid arterial bed of the anaesthetised dog have been described in the art. These include indole derivatives such as those disclosed inter alia in published British Patent Specifications Nos. 2982175, 2081717, 2083463, 2124210, 2150932, 2162522, 2168347, 2168973, 2185020, 2186874, 2191488, 2208646, published European Patent Specifications Nos. 147107, 237678, 242939, 244085, 225726, 254433, 303506, 313397, 354777, 382570, 464558, 506363, 506369, 450238, 451022, 451008, 478954, 438230, 494774, 497512, 501568 and published International patent application Nos. WO92/11013, WO92/11014, WO92/06973, WO93/00086, WO92/13856, WO93/00094, WO91/18897 and WO93/00333.
The compounds disclosed in the aforementioned patent specifications have been described as useful in treating and/or preventing pain resulting from dilatation of the cranial vasculature, in particular migraine and related disorders such as cluster headache.
We now find that such compounds are also of use in the treatment of certain ocular disorders.
Glaucoma is a serious progressive clinical condition caused by an imbalance in the flow of intraocular fluids, leading to elevated intraocular pressure, optic nerve degeneration and eventual blindness. Current medical therapy for glaucoma is dominated by pharmacological agents which act by reducing the flow of fluid into the ocular chamber, for example beta blockers, and the side-effect profiles of such drugs severely limit their clinical use. Thus, there is a real need to develop new medicines in this area of ophthalmic disease.
Surprisingly, compounds which are selective 5-HT.sub.1 -like receptor agonists reduce elevated intraocular pressure and are effective in the treatment of glaucoma.
According to one aspect of the invention we therefore provide a selective 5-HT.sub.1 -like receptor agonist or a physiologically acceptable salt or solvate thereof for use in the treatment or prevention of elevated intraocular pressure, in particular glaucoma e.g. high tension glaucoma and low tension glaucoma.
Particularly preferred compounds for use in the treatment or prevention of elevated intraocular pressure are N-methyl-3-(1-methyl-4-piperidinyl)-1H-indole-5-ethanesulphonamide, especially may be represented by the formula (I) ##STR1## and its physiologically acceptable salts and solvates are disclosed in GB 2162522. Numerous clinical studies have demonstrated the effectiveness of the compound of formula (I) (generic name sumatriptan) in migraineurs.
Thus, a particularly preferred aspect the present invention provides the compound of formula (I) or a physiologically acceptable salt or solvate thereof for use in the treatment or prevention of elevated intraocular pressure.
In an alternative or further aspect, the invention provides a method of treatment of a mammal, including man, suffering from or susceptible to elevated intraocular pressure which comprises administering an effective amount of a selective 5-HT.sub.1 -like receptor agonist or a physiologically acceptable salt or solvate thereof.
It will be appreciated that whilst selective 5-HT.sub.1 -like receptor agonists will primaril
REFERENCES:
Barnett et al., Exp. Eye Res., 57, 2, Aug. 1993, 209-216.
Tobin et al., J. Neurochem., 53, 3, Sep. 1989, 686-691.
Meyer-Bothling et al., Invest. Ophthalmol. Vis. Sci., 34, 10, Sep. 1993, 3035-3042.
Zschauer et al., Am. J. Physiol., 261, 6Pt2, Dec. 1991, H1819-H1827.
Osborne et al., Neurochem. Int., 19, 4, 1991, 407-411.
Osborne et al., Neurol. Neurobiol., 49, 1989, 159-175.
Mangel et al., Vis. Neurosci., 8, 3, Mar. 1992, 213-218.
Fay Zohreh
Glaxo Group Limited
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