Peripherally active anti-hyperalgesic opiates
AssigneeThe Regents of the University of California
InventorTony L. Yaksh
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Abstract
Methods using compositions for the treatment of peripheral hyperalgesia are provided. The compositions contain an anti-hyperalgesia effective amount of one or more compounds that directly or indirectly interact with peripheral opiate receptors, but that do not, upon topical or local administration, elicit central nervous system side effects. The anti-diarrheal compound 4-(p-chlorophenyl)-4-hydroxy-N-N-dimethyl-.alpha.,.alpha.-diphenyl-1-piper idinebutyramide hydrochloride is preferred for use in the compositions of the claimed methods.
Claims11
A method of treating peripheral hyperalgesia, comprising topically applying or locally administering to a mammal in need of such treatment an effective amount of a composition, comprising an anti-hyperalgesically effective amount of one or more compound(s) in a vehicle formulated for topical application or local administration, wherein the compound is an anti-diarrheal compound that:
- (a) has activity as a peripheral anti-hyperalgesic;
- and
- (b) a B/A ratio greater than diphenoxylate, wherein:
- B is the ED.sub.50 of the compound in an assay that measures central nervous system (CNS) activity of the compound;
- the assay in which B is determined is a tail clip or hot plate analgesic assay;
- A is the ED.sub.50 of the compound in an assay that measures anti-diarrheal activity of the compound;
- the assay in which anti-diarrheal activity is measured is a Castor oil test or an assay that measures antagonism by the compound of prostaglandin E.sub.2 (PGE.sub.2)-induced diarrhea;
- and
- the relative activities of the compound are compared to the activities of diphenoxylate in the same assays.
A method of treating peripheral hyperalgesia, comprising topically applying or locally administering to a mammal in need of such treatment an effective amount of a composition comprising in a vehicle formulated for topical or local administration an anti-hyperalgesically effective amount of 4-(p-chlorophenyl)-4-hydroxy-N-N-dimethyl-.alpha.,.alpha.-diphenyl-1-piper idinebutyramide monochloride that has the formula:
- ##STR48## or a pharmaceutically acceptable salt or acid thereof.
A method of treating peripheral hyperalgesia, comprising topically applying or locally administering to a mammal in need of such treatment, an effective amount of a composition comprising an anti-hyperalgesically effective amount of one or more compound(s) in a vehicle formulated for topical application or local administration, wherein the composition comprises 4-(p-chlorophenyl)-4-hydroxy-N-N-dimethyl-.alpha.,.alpha.-diphenyl-1-piper idinebutyramide, N-oxide that has the formula:
- ##STR49## or a pharmaceutically acceptable salt or acid thereof.
A method of treating pain or irritation associated with peripheral hyperalgesia, comprising topically applying to a mammal in need of such treatment an effective amount of a 4-(p-chlorophenyl)-4-hydroxy-N,N-dimethyl-.alpha.,.alpha.-diphenyl-1-piper idinebutyramide monochloride.
A method of treating pain or irritation associated with peripheral hyperalgesia, comprising locally administering to a mammal in need of such treatment an effective amount of a 4-(p-chlorophenyl)-4-hydroxy-N,N-dimethyl-.alpha.,.alpha.-diphenyl-1-piper idinebutyramide monochloride.
Dependencies are inferred from the claim text.