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Pathway Description
Droxidopa A1-Adrenergic Vasoconstriction Action Pathway
Homo sapiens
Category:
Metabolite Pathway
Sub-Category:
Drug Action
Created: 2023-07-17
Last Updated: 2023-11-27
Droxidopa is a medication used to treat symptomatic neurogenic orthostatic hypotension (nOH) caused by dopamine beta-hydroxylase deficiency, non-diabetic autonomic neuropathy and primary autonomic failure caused by conditions such as Parkinson's disease. Droxidopa is a precursor of noradrenaline that is used in the treatment of Parkinsonism. Droxidopa is an orally active synthetic precursor of norepinephrine that increases the deficient supply of norepinephrine in patients with NOH, thereby improving orthostatic blood pressure and alleviating associated symptoms of lightheadedness, dizziness, blurred vision, and syncope through the induction of tachycardia (increased heart rate) and hypertension. Norephinephrine acts at alpha-adrenergic receptors as a vasoconstrictor and at beta-adrenergic receptors as a heart stimulator and artery dilator. At the alpha-1 adrenergic receptor, droxidopa as epinephrine acts as a vasoconstrictor by contracting the smooth muscles. Norepinephrine activates the alpha-1 adrenergic receptor which activates the Gq protein cascade. This activates Phospolipase C which catalyzes Phosphatidylinositol 4,5-bisphosphate into Inositol 1,4,5-trisphosphate and Diacylglycerol. Diacylglycerol activates protain kinase C which activates the voltage-dependent calcium channel, allowing calcium to enter the cell. Inositol 1,4,5-trisphosphate activates Inositol 1,4,5-trisphosphate receptor on the sarcoplasmic reticulum which also allows calcium to enter the cell from the sarcoplasmic reticulum. This high concentration of calcium in the cytosol attaches to calmodulin which activates Myosin light chain kinase. This enzyme catalyzes Myosin light chain 3 into myosin LC-P which causes myosin to bind to actin and contract the muscle cell. The contraction of this smooth muscle causes the blood vessel to constrict. Some side effects of using droxidopa may include headache, dizziness, nausea, high blood pressure, and fainting.
References
Droxidopa A1-Adrenergic Vasoconstriction Pathway References
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