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Pathway Description
Methyldopa Action Pathway
Homo sapiens
Drug Action Pathway
Created: 2022-01-31
Last Updated: 2023-10-25
Methyldopa is a centrally-acting alpha-2 adrenergic agonist used to manage hypertension alone or in combination with hydrochlorothiazide, and to treat hypertensive crises.
Alpha-adrenergic receptors are essential for the regulation of blood pressure in humans. Two types of alpha receptors, alpha 1 and alpha 2, both play a role in regulating blood pressure. Alpha-1 receptors are postsynaptic (located after the nerve junction, or space between a nerve fiber and target tissue). In this case, the target tissue is the vascular smooth muscle. Activation of the alpha-1 receptor activates the Gq signaling cascade, which activates phospholipase C. Phospholipase C converts phosphatidylinositol 4,5-bisphosphate to diacylglycerol and inositol 1,4,5-trisphosphate (IP3). IP3 activates the IP3 receptor on the sarcoplasmic reticulum, leading to calcium influx into the cytosol from the sarcoplasmic reticulum. Calcium binds to calmodulin and activates myosin light chain kinase. Myosin light chain kinase is responsicle for phosphorylating myosin light chain. Phosphorylated myosin light chain binds to actin and causes muscle contraction.
Alpha-2 adrenergic receptors on the presynaptic neurons are activated by noradrenaline in the synaptic cleft. Once activated, the trigger the Gi signaling cascade, which inhibits the calcium channel, reducing calcium in the neuron. Low concentration of calcium prevents the release of norepinephrine into the synapse. As a result, there is less stimulation of alpa-1 adrenergic receptors and reduced muscle contraction in blood vessels. Methyldopa activates these autoreceptors on the presynaptic membrane, thus reducing blood pressure.
Common side effects of methyldopa include nausea, diarrhea, headache, dizziness, sedation, dry mouth, rash.
References
Methyldopa Pathway References
Gupta M, Al Khalili Y: Methyldopa
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