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Pathway Description
Diphenoxylate Opioid Agonist Action Pathway
Homo sapiens
Category:
Metabolite Pathway
Sub-Category:
Drug Action
Created: 2020-11-30
Last Updated: 2023-10-25
Diphenoxylate is an oral anti-diarrheal drug. It targets the enteric nervous system of the GI tract. Its main function is to reduce GI motility, slowing the movement of food through the intestine, allowing more solute and water reabsorption. Diphenoxylate binds to opioid receptors, mainly the mu-type, on presynaptic cholinergic neurons in the enteric nervous system. The mu-type opioid receptors are coupled to Gi and Go proteins. The Gi cascade results in an inhibition of adenylate cyclase, which reduces cytosolic cAMP. Protein kinase A is activated by cAMP to open Ca2+ channels and allow Ca2+ influx into the cytosol. A reduction in cAMP reduces the activity of protein kinase A and thus reduces the cytosolic Ca2+. The Go signaling cascade results in activation of K+ channels and inhibition of Ca2+ channels. Activated K+ channels allow K+ influx into the neuron, causing hyperpolarization of the neuron and making neuronal firing more difficult. Inhibiting Ca2+ channels prevents Ca2+ entry into the neuron, consequently, synaptic vesicles containing acetylcholine are prevented from docking at the membrane and releasing acetylcholine into the synapse. Less acetylcholine is available in the synapse to bind to post synaptic muscarinic receptors (M3) on the muscle of the Gi tract. This means that less M3 receptors are activated on the muscle, so less contraction occurs. This is important in treating diarrhea as it reduces peristalsis. The food remains in the gut longer undergoing segmentation and more solute and water reabsorption occurs. Side effects such as confusion, constipation, drowsiness, euphoria, dizziness, headache, respiratory depression, abdominal bloating and pain, nausea and vomiting, restlessness, numbness of extremities and Allergic reactions including anaphylaxis, urticaria, angioneurotic edema, swelling of the gums, pruritus.
References
Diphenoxylate Opioid Agonist Pathway References
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