Method for identifying adrenergic receptor antagonists having good tolerability
AssigneeUniversity Technology Corporation
InventorsMichael R. Bristow, J. David Port
Life of this patent
Estimating the term…
Abstract
Disclosed are methods to identify adrenergic receptor antagonists having good tolerability. These methods include measuring the inverse agonist activity and/or the intrinsic sympathomimetic activity of an adrenergic receptor antagonist. Also disclosed are a method to treat heart failure and compounds useful therefor.
Claims28
A method to identify a β1 adrenergic receptor antagonist having good tolerability, comprising:
- (a) identifying an adrenergic receptor antagonist which binds to a β1 adrenergic receptor;
- (b) measuring the basal adrenergic receptor signaling activity of said β1 adrenergic receptor;
- (c) contacting said β1 adrenergic receptor and said adrenergic receptor antagonist;
- (d) measuring the inverse agonist activity of said adrenergic receptor antagonist on said β1 adrenergic receptor;
- and
- (e) identifying adrenergic receptor antagonists having less than about 50% inverse agonist activity.
A method to identify an adrenergic receptor antagonist having good tolerability, comprising:
- (a) measuring the basal adrenergic receptor signaling activity of an adrenergic receptor;
- (b) measuring the inverse agonist activity of an adrenergic receptor antagonist on said adrenergic receptor;
- (c) identifying adrenergic receptor antagonists having less than about 50% inverse agonist activity;
- (d) measuring the intrinsic sympathomimetic activity of the adrenergic receptor antagonist;
- and
- (e) identifying adrenergic receptor antagonists having less than about 30% intrinsic sympathomimetic activity.
A method to identify an adrenergic receptor antagonist having good tolerability, comprising:
- (a) identifying an adrenergic receptor antagonist which binds to an adrenergic receptor expressed by a recombinant cell;
- (b) measuring the basal adrenergic receptor signaling activity of said adrenergic receptor;
- (c) measuring the inverse agonist activity of said adrenergic receptor antagonist on said adrenergic receptor;
- (d) measuring the intrinsic sympathomimetic activity of said adrenergic receptor antagonist on said adrenergic receptor;
- and
- (e) identifying adrenergic receptor antagonists having less than about 50% inverse agonist activity and less than about 30% intrinsic sympathomimetic activity.
A method to treat heart failure, comprising:
- (a) identifying the need for stabilization of heart function in a patient with heart failure;
- and
- (b) administering to said patient an effective amount of an adrenergic receptor antagonist which has less than about 50% inverse agonist activity and less than about 10% intrinsic sympathomimetic activity with respect to said adrenergic receptor.
Dependencies are inferred from the claim text.