Caffeine and Partial A2A Agonist Composition for Myocardial Imaging
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Solution Overview
Problem
Current myocardial perfusion imaging techniques face challenges in achieving rapid and maximal coronary vasodilation without peripheral vasodilation, leading to patient discomfort and the need for multiple dosing due to the short half-life of adenosine and side effects from existing adenosine receptor agonists.
Innovation Solution
A pharmaceutical composition comprising caffeine and a partial A2A receptor agonist, such as CVT-3033 or Regadenoson, administered in a single intravenous bolus to achieve a therapeutically effective increase in coronary blood flow with minimal peripheral effects, allowing for improved patient tolerability during myocardial stress perfusion imaging.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If adenosine is used as a vasodilator, then coronary blood flow increases, but peripheral vasodilation and side effects occur
Solution Approach 1:
The patent applies local quality by using a selective A2A adenosine receptor agonist that targets coronary arteries specifically. The compound (4S,2R,3R,5R)-2-[6-amino-2-(1-benzylpyrazol-4-yl)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol selectively activates A2A receptors in the coronary circulation, producing localized vasodilation without causing widespread peripheral vasodilation. This selective targeting allows coronary blood flow increase while avoiding the harmful peripheral effects associated with non-selective adenosine agonists.
2Productivity
If adenosine is used for vasodilation, then imaging can be performed, but multiple dosing is required due to short half-life
Solution Approach 1:
The patent applies preliminary action by pre-administering the selective A2A agonist before the imaging protocol begins. The compound has a sufficiently long half-life to maintain effective coronary vasodilation throughout the entire imaging sequence, eliminating the need for repeated dosing. This preliminary establishment of vasodilation ensures continuous imaging capability without time loss from repeated administration.
3Speed
If potent A2A receptor agonists are used, then coronary vasodilation is achieved, but duration of action is too long for imaging
Solution Approach 1:
The patent applies partial action by using a selective A2A agonist with optimized pharmacological properties. The compound provides sufficient and sustained vasodilation for the imaging procedure without excessive duration that would be problematic. The selective A2A receptor activation delivers just the right amount of vasodilatory effect needed for imaging, avoiding both insufficient action and excessive prolonged action.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The combination of caffeine and partial A2A receptor agonists provides a rapid and sustained increase in coronary blood flow with reduced duration of action, minimizing side effects and the need for multiple dosing, thereby enhancing patient tolerability and imaging efficacy.
Implementation Method 1
Adenosine, a naturally occurring nucleoside, exerts its biological effects by interacting with a family of adenosine receptors characterized as subtypes A1, A2A, A2B, and A3
Implementation Method 2
The partial A2A receptor agonist... provides a rapid and sustained increase in coronary blood flow
Implementation Method 3
Caffeine is an adenosine A1 receptor antagonist
Data Source
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AI summary
The present application discloses methods and compositions for increasing patient tolerability during myocardial imaging comprising the administration of doses of caffeine and one or more adenosine A2A receptor agonists to a mammal undergoing myocardial imaging.