Methods for protecting tissues and organs from ischemic damage

Details Methods for protecting tissues and organs from ischemic damage Methods for protecting tissues and organs from ischemic damage

1993-03-15

1995-08-22

Page, Thurman K.

Drug, bio-affecting and body treating compositions

Preparations characterized by special physical form

Implant or insert

424451, 424464, 424489, 514936, 604 51, A61F 202, A61K 948, A61K 920, A61K 914

Patent

active

054438365

ABSTRACT:
Methods for protecting tissues and organs including the heart central nervous system, and kidney from ischemic damage are described and claimed based upon the recognition that protection against infarction is mediated by A3 rather than A1 adenosine receptors, as was previously thought, and that the receptor mediating protection in other organs and tissues has not been defined. Methods for selectively stimulating A3 adenosine receptors are described and claimed, as such selection is shown to prevent or substantially reduce cell death resulting from ischemia with or without reperfusion in humans. According to this invention, the A3 adenosine receptor is selectively stimulated by administering a compound which is an A3 adenosine receptor-selective agonist. Prevention of tissue death is also achieved by administering a compound which is a non-selective adenosine receptor agonist together with compounds that act as antagonists to the A1 and A2 adenosine receptors.

REFERENCES:
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Liu, Y. and J. M. Downey, Ischemic preconditioning protects against infarctionin rat heart. Am J. Physiol. 1992; 263:H1107-H1112.
Liu, G. S., et al., Protection Against Infraction Afforded by Preconditioning is Mediated by A1 Adenosine Receptors in Rabbit Heart. Circulation 1991; 84:350-356.
Olsson R. A., and J. D. Pearson, Cardiovascular Purinoceptors. Physiol. Rev. 1990; 70:761-845.
Downey, J. M., et al, Adenosine and the anti-infarct effects of preconditioning. Cardiovascular Research 1993; 27:3-8.
Thornton, J. D., et al, Intravenous Pretreatment with Al-Selective Adenosine Analogues Protects the Heart Against Infarction. Circulation, 1992; 85:659-665.
Jacobson, K. A., Adenosine Receptors: Pharmacology, Structure-Activity Relationships, and Therapeutic Potential. J. Med. Chem. 1992; 35:407-422.
Walsh, R. S., et al., Role of Adenosine Receptor Subtypes in Preconditioning. JACC 1993; 21:116A.
Downey, J. M., Cardioprotective Role of A1 Receptor Ligands. J. Mol. Cell Cardiol. 1992; Y24:S.32.
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