Method for determining drug compositions to prevent desensitizat

Details Method for determining drug compositions to prevent desensitizat Method for determining drug compositions to prevent desensitizat

1995-03-21

1997-01-28

Mosher, Mary E.

Chemistry: molecular biology and microbiology

Measuring or testing process involving enzymes or...

Involving antigen-antibody binding, specific binding protein...

435 72, 436501, G01N 33567

Patent

active

055976999

ABSTRACT:
Drug compositions combining antagonists with agonists to prevent desensitization of cellular receptors. An agonist is a substance or drug that produces a maximal or nearly maximal response, whereas an antagonist is a substance or molecule that produces no response, but can block the action of the agonist/drug. A partial agonist produces a moderate response and can also block the response of the receptor to the agonist/drug. The instant invention solves the problem of determining the optimal concentration of an antagonist or inhibitor which is necessary to prevent desensitization, without causing unnecessary and unwanted inhibition, by providing a formulative method detailing how a competitive antagonist of the receptor should be combined with an agonist in a specific proportion to maximize and maintain receptor response throughout drug therapy/administration.

REFERENCES:
Fernandes et al., "B-Adrenoceptordesensitization in guinea-pig etc. . . ", European Journal of Pharmacology, 157:135-145, 1988.
Dilger et al, "Direct Measurement . . . Channel"; Biophys. J Biophysical Society; vol. 57(Apr.):723-731, 1990.
Geoffroy et al; "Reduction of Desensitization . . . by Antagonists"; Molecular Pharamacology, 39:587-591, 1991.
Stephenson--A modification of Receptor Theory--; Brit. J. Pharmacol., 11, 379-393, 1956.
Keen--Testing Models of Agonism for G protein--coupled receptors--; TIPS--vol. 12:371-375, 1991.
Colquhoun--Validity of the Operational Model; Trends in Pharm. Sci.(TIPS) vol. 10:17, 1989.

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