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Inhibition of excessive phospholipase A.sub.2 activity and/or production by non-antimicrobial tetracyclines
| Details |
Inventors: Pruzanski, Waldemar; Golub, Lorne M.; Vadas, Peter; Greenwald, Robert A.; Ramamurthy, Nangavarum S.; McNamara, Thomas F.;
Assignee: The Research Foundation of State Univ. of New York (Albany, NY)
Primary Examiner: MacMillan; Keith D.
Assistant Examiner:
Attorney, Agent or Firm: Hoffman & Baron, LLP
A method for treating mammals suffering from conditions associated with excess phospholipase A.sub.2 activity and/or production comprising administering to the mammal an effective amount of a non-antimicrobial tetracycline sufficient to inhibit excess phospholipase A.sub.2 activity and/or production is disclosed. A pharmaceutical composition is also disclosed. |
|
DETAILED DESCRIPTION The present invention provides a method for treating mammals suffering from conditions associated with excess phospholipase A.
sub.
2 activity and/or production which includes administering to the mammal an amount and/or type of a tetracycline which inhibits the excess PLA.
sub.
2 activity and/or production but which is non-antimicrobial.
Non-limiting examples of conditions or diseases associated with excess PLA.
sub.
2 activity and/or production include rheumatoid arthritis, other tissue-destructive conditions, sepsis, septic shock, pancreatitis, malaria, psoriasis, inflammatory bowel diseases and multisystem organ failure among others.
Chemically-modified non-antimicrobial tetracyclines, for example dedimethylaminotetracyclines are useful in the present invention.
Dedimethylaminotetracyclines include 4-dedimethylaminotetracycline, 4-dedimethylamino-5-oxytetracycline, 4-dedimethylamino-7-chloro-tetracycline, 4-hydroxy-4-dedimethylaminotetracycline, 5a,6-anhydro-4-hydroxy-4-dedimethylaminotetracycline, 6.
alpha.
-deoxy-5-hydroxy-4-dedimethylaminotetracycline, 6-demethyl-6-deoxy-4-dedimethylaminotetracycline, 4-dedimethylamino-12a-deoxytetracycline, 4-dedimethylamino-11-hydroxy-12a-deoxytetracycline and 4-dedimethylamino-7-dimethylaminotetracycline.
Further examples of chemically-modified tetracyclines useful in the present invention are 6a-benzylthiomethylenetetracycline, the 2-nitrilo analogs of tetracycline, the mono-N-alkylated amide of tetracycline, 6-fluoro-6-demethyltetracycline, 11a-chlorotetracycline and 12a-deoxytetracycline and its derivatives.
The tetracyclines may be coupled with a pharmaceutically acceptable carrier.
The present invention also provides a method for treating mammals suffering from conditions associated with excess phospholipase A.
sub.
2 activity and/or production which includes the administration to the mammal of (i) an amount and/or type of a tetracycline that effectively inhibits excess PLA.
sub.
2 activity and/or production and (ii) an amount of a classical therapeutic agent which, when combined with the effectively anti-PLA
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