Droxidopa Norepinephrine Precursor for Hypotension Treatment
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Solution Overview
Problem
Current treatments for neurally mediated hypotension are often ineffective and come with undesirable side effects, requiring prolonged trial-and-error with various drug combinations, which can be risky and not adequately address the condition.
Innovation Solution
Pharmaceutical compositions comprising droxidopa alone or in combination with other pharmaceutically active compounds, such as antidepressants, DOPA decarboxylase inhibitors, catechol-O-methyltransferase inhibitors, and cholinesterase inhibitors, to treat neurally mediated hypotension by increasing norepinephrine levels and improving blood pressure regulation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If known treatments for neurally mediated hypotension are used, then blood pressure regulation is attempted, but undesirable side effects occur and treatment effectiveness is insufficient
Solution Approach 1:
The patent changes the pharmacological parameter by using droxidopa, a synthetic amino acid precursor of norepinephrine, which is converted directly to norepinephrine via dopa decarboxylase. This parameter change results in more targeted and effective treatment with fewer side effects compared to conventional treatments like fludrocortisone, beta-blockers, and disopyramide.
Solution Approach 2:
The patent introduces droxidopa as an intermediary substance that is converted to norepinephrine in the body. This intermediary approach allows for more controlled and effective norepinephrine replenishment without the harsh side effects of direct norepinephrine administration or conventional blood pressure regulators.
2Reliability
If multiple drug combinations are trialed to treat neurally mediated hypotension, then treatment effectiveness is sought, but time is lost and complexity increases
Solution Approach 1:
The patent performs preliminary action by identifying and preparing droxidopa as a synthetic amino acid precursor that can be directly converted to norepinephrine. This preliminary preparation of the active substance eliminates the need for extensive trial-and-error with multiple drug combinations, allowing for more rapid and targeted treatment initiation.
3Reliability
If conventional treatments are used, then blood pressure is regulated, but the condition is not adequately addressed and recurrence occurs
Solution Approach 1:
The patent changes the pharmacological approach by using droxidopa, which is converted to norepinephrine via dopa decarboxylase. This parameter change enables more adequate and sustained treatment of neurally mediated hypotension, addressing the root cause more effectively and reducing symptom recurrence compared to conventional treatments.
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 use of droxidopa in combination with other active agents effectively reduces or eliminates symptoms of neurally mediated hypotension, such as dizziness and fatigue, and prevents their recurrence, offering a more targeted and safer treatment option compared to existing therapies.
Implementation Method 1
Droxidopa is directly converted to 1-norepinephrine by the action of the aromatic L-amino acid decarboxylase which is widely distributed in a living body
Implementation Method 2
it shows various actions, as norepinephrine, via the adrenaline receptors in various tissues
Implementation Method 3
block the body's response to adrenaline, which can kick-start the blood pressure abnormality
Data Source
Figure 1
AI summary
The present invention is directed to methods of treating neurally mediated hypotension. In particular, the invention provides pharmaceutical compositions comprising droxidopa alone, or in combination with one or more further active ingredients, that can be administered to a patient for the treatment of neurally mediated hypotension.