A method of increasing aqueous humor outflow in the eye of a human patient including topically administering to the eye an outflow increasing amount of a compound characterized in that it contains one or more groups capable of reacting with sulfhydryl groups in the trabecular meshwork of the eye, and it has a margin of safety of at least 2.0.
The present invention provides compounds represented by the following general formula [I] and salts thereof, which are useful as therapeutic agents for glaucoma, ##STR1## wherein R.sup.1 is H, lower alkyl or phenyl, and the phenyl can be substituted by lower alkyl, hydroxy, lower alkoxy, halogen, nitro or phenyl; R.sup.2 and R.sup.3, being the same or different, are H, halogen or lower alkyl; R.sup.4 and R.sup.5, being the same or different, are H, lower alkyl or carboxyl or ester thereof; and R.sup.6 is carboxyl or phosphono or ester thereof.
Pharmaceutical compositions and a method are disclosed for treating glaucoma and/or ocular hypertension in the mammalian eye by administering to the mammalian eye the pharmaceutical composition of the invention which contains as the active ingredient one or more compounds having guanylate cyclase inhibition activity. Examples of guanylate cyclase inhibitors utilized in the pharmaceutical composition and method of treatment are methylene blue, butylated hydroxyanisole and N-methylhydroxylamine.
Pharmaceutical compositions and a method are disclosed for treating glaucoma and/or ocular hypertension in the mammalian eye by administering to the mammalian eye the pharmaceutical composition of the invention which contains as the active ingredient one or more compounds having guanylate cyclase inhibition activity. Examples of guanylate cyclase inhibitors utilized in the pharmaceutical composition and method of treatment are: ##STR1## and pharmaceutically acceptable salts thereof.
A method for treating glaucoma in an eye of a human patient is disclosed. The method comprises the step of chronically, orally administering to the patient an unsaturated ketone derivative of an aryloxyacetic acid in an amount sufficient to safely and effectively lower intraocular pressure in the human eye. The unsaturated ketone derivative is selected from the group consisting of ethacrynic acid, an analog of ethacrynic acid, an ester derivative of ethacrynic acid, an ester derivative of an ethacrynic acid analog, an amide derivative of ethacrynic acid, an amide derivative of an ethacrynic acid analog, a pharmaceutically acceptable salt of ethacrynic acid, a pharmaceutically acceptable salt of an ethacrynic acid analog, a pharmaceutically acceptable salt of the ester derivative, a pharmaceutically acceptable salt of the amide derivative, and mixtures thereof. The amount administered is preferably between about 50 mg and about 75 mg two times per day.
Methods for the treatment of glaucoma are described. The compounds described cause a perturbation of cell adhesions in the trabecular meshwork, mainly via disruption of the associated cytoskeletal structures or the modulation of their interactions with the underlying membrane. Perturbation of these adhesions reduces the resistance of the trabecular meshwork to fluid flow and thereby reduces intraocular pressure.
