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Pathway Description
Drotaverine Action Pathway
Homo sapiens
Drug Action Pathway
Created: 2022-03-28
Last Updated: 2023-10-25
Drotaverine is a phosphodiesterase-4 inhibitor used to alleviate gastrointestinal and genitourinary smooth muscle spasms.
In these organs, smooth muscle contraction is stimulated by acetylcholine activating M3 muscarinic receptors. M3 muscarinic receptors are coupled to Gq protein, and thus, activation of this receptors triggers the Gq signaling cascade. This leads to activation of phospholipase C. Phospholipase C then converts PIP2 (Phosphatidylinositol 4,5-bisphosphate) to inositol-1,4,5-triphosphate (IP3) and diacylglycerol. IP3 stimulates IP3 receptors on the endoplasmic reticulum(ER), leading to the release of calcium into the cytosol from the ER. Calcium binds to the protein calmodulin. This calcium-calmodulin complex activates myosin light chain kinase. Myosin light chain kinase produces muscle contraction by phosphorylating myosin light chain.
Diacylglycerol, the other product of M3 receptor activation, activates protein kinase C (PKC). PKC inhibits myosin light chain phosphatase. The role of myosin light chain phosphatase is to dephosphorylate the phosphorlyated myosin light chain to stop contraction. By inhibiting this enzyme, contraction is produced.
cAMP can produce muscle relaxation by activating protein kinase A (PKA). PKA phosphorylates myosin light chain kinase, thereby inactivating it and preventing it’s phosphorylation of myosin light chain. This leads to an accumulation of unphosphorylated myosin light chain and ultimately, muscle relaxation.
Drotaverine’s function is to inhibit phosphodiesterase 4A, the enzyme which metabolizes cAMP in smooth muscles. By inhibiting this enzyme, this causes a build up of cAMP, and therefore, contributes to decrease muscle spasms by favoring muscle relaxation.
References
Drotaverine Pathway References
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