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Details for Patent: 5,668,155

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Details for Patent: 5,668,155

Title: Administration of pirenzepine, methyl scopolamine and other muscarinic receptor antagonists for treatment of lipid metabolism disorders
Abstract:Disclosed are methods for improving various aberrant metabolic indices in mammals including humans by administration of muscarinic (particularly M1) receptor antagonists alone or in combination with prolactin inhibiting compounds. Preferably the administration takes place at a predetermined time (or, if a combination of muscarinic receptor antagonist and prolactin inhibitor is used, at different predetermined times) during a 24-hour period when the administration is effective (or its effect more pronounced). The invention has application in the treatment of lipid and glucose metabolism disorders.
Inventor(s): Cincotta; Anthony H. (Andover, MA), Meier; Albert H. (Baton Rouge, LA), Wilson; John M. (Charlestown, MA)
Assignee: The General Hospital Corporation (Boston, MA) The Board of Supervisors of Louisiana State University and Agricultural (Baton Rouge, LA)
Filing Date:Jun 20, 1994
Application Number:08/263,607
Claims:1. A method for altering lipid metabolism in a vertebrate subject in need of such treatment comprising administering to said subject an amount of a muscarinic receptor antagonist selective for the M1 muscarinic receptor, said administration taking place at a predetermined time during a 24-hour period, said time and said amount being effective to accomplish at least one of: decreasing hyperlipoproteinemia, decreasing triglycerides, reducing body fat stores, and increasing the ratio of high-density to low-density lipoproteins in said subject.

2. The method of claim 1 wherein said subject is a mammal.

3. The method of claim 2 wherein said subject is human.

4. The method of claim 1 or 2 wherein said muscarinic receptor antagonist selective for the M1 muscarinic receptor is selected from the group consisting of:

methantheline, ipratropium, propantheline, dicyclomine, scopolamine, methylscopolamine, telenzepine, benztropine, QNX-hemioxalate, hexahydro-sila-difenidol hydrochloride and pirenzepine.

5. The method of claim 4 wherein said muscarinic receptor antagonist selective for the M1 muscarinic receptor is selected from the group consisting of pirenzepine and methyl scopolamine.

6. A method for regulating lipid metabolism in a vertebrate subject in need of such treatment comprising administering to said subject an amount of a muscarinic receptor antagonist selective for the M1 muscarinic receptor, and an amount of a prolactin inhibitor, said amounts in combination being effective to accomplish at least one of decreasing hyperlipoproteinemia, decreasing triglycerides, reducing body fat stores, and increasing the ratio of high-density to low-density lipoproteins in said subject.

7. The method of claim 6 wherein said muscarinic receptor antagonist selective for the M1 muscarinic receptor is selected from the group consisting of:

methantheline, ipratropium, propantheline, dicyclomine, scopolamine, methylscopolamine, telenzepine, benztropine, QNX-hemioxalate, hexahydro-sila-difenidol hydrochloride and pirenzepine.

8. The method of claim 7 wherein said prolactin inhibitor is selected from the group consisting of d2 dopamine agonists and prolactin-inhibiting ergot alkaloids.

9. The method of claim 6 wherein said muscarinic receptor antagonist selective for the M1 muscarinic receptor is selected from the group consisting of methantheline, ipratropium, propantheline, dicyclomine, scopolamine, methylscopolamine, telenzepine, QNX-hemioxalate, hexahydro-siladifenidol hydrochloride and pirenzepine and said prolactin inhibitor is selected from the group consisting of 2-bromo-alpha-ergocriptine, 6-methyl-8 beta-carbobenzyloxyaminoethyl-10-alpha-ergoline, 8-acylaminoergolines, 6-methyl-8-alpha-(N-acyl) amino-9-ergoline, 6-methyl-8 alpha-(N-phenylacetyl)amino-9-ergoline, ergocornine, 9,10-dihydroergocornine, D-2-halo-6-alkyl-8-substituted ergolines, D-2-bromo-6-methyl-8-cyanomethylergoline, carbidopa, benserazide, L-dopa, and non toxic salts thereof.

10. The method of claim 9 wherein said subject is human.

11. The method of claim 10 wherein said muscarinic receptor antagonist selective for the M1 muscarinic receptor is selected from the group consisting of methylscopolamine and pirenzepine, and said prolactin-inhibiting compound is bromocriptine.

12. The method of any one of claims 6 and 7, said administration of said muscarinic receptor antagonist selective for the M1 muscarinic receptor taking place at a first predetermined time within a 24-hour period at which the lipid metabolism of said mammal is responsive to said antagonist.

13. The method of claim 12, said administration of said prolactin inhibitor taking place simultaneously with the administration of said muscarinic receptor antagonist selective for the M1 muscarinic receptor.

14. A method for altering lipid metabolism in a vertebrate animal or human subject in need of such treatment comprising administering to said subject an amount of a muscarinic receptor antagonist selective for the M1 muscarinic receptor, said amount being effective to accomplish at least one of: decreasing hyperlipoproteinemia, decreasing triglycerides, and increasing the ratio of high-density to low-density lipoproteins in said subject.

15. The method of claim 14 wherein said subject is not suffering from diabetes.
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