PathWhiz ID | Pathway | Meta Data |
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PW127991View Pathway |
drug action
Trihexyphenidyl Action PathwayHomo sapiens
Trihexyphenidyl is an antispasmodic drug used as an adjunct drug in the management of parkinsonism and as a treatment for extrapyramidal symptoms caused by drugs affecting the central nervous system (CNS). Trihexyphenidyl is a non-selective muscarinic acetylcholine receptor antagonist but binds with higher affinity to the M1 subtype. In vivo studies have shown that trihexyphenidyl demonstrates higher affinity for central muscarinic receptors located in the cerebral cortex and lower affinity for those located peripherally. Other studies suggest that trihexyphenidyl may modify nicotinic acetylcholine receptor neurotransmission, leading indirectly to enhanced dopamine release in the striatum. Although the anticholinergic has proven to be useful in the treatment of symptoms associated with Parkinson’s disease or other movement disorders, its mechanism of action has yet to be fully elucidated. The precise mechanism of action of trihexyphenidyl remains inadequately comprehended; it appears to act on the parasympathetic nervous system by inhibiting efferent impulses directly. Structures innervated by the parasympathetic system, such as the salivary glands, eyes, and smooth muscles (directly and indirectly), are affected, even at smaller doses. Possible side effects of using Trihexyphenidyl may include dry mouth, constipation, nausea, and vomiting. Trihexyphenidyl is administered as an oral tablet.
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Creator: Hayley Created On: June 27, 2023 at 13:53 Last Updated: June 27, 2023 at 13:53 |
PW144502View Pathway |
drug action
Trihexyphenidyl Drug Metabolism Action PathwayHomo sapiens
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Creator: Ray Kruger Created On: October 07, 2023 at 13:46 Last Updated: October 07, 2023 at 13:46 |
PW146914View Pathway |
drug action
Trilaciclib Drug Metabolism Action PathwayHomo sapiens
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Creator: Ray Kruger Created On: October 07, 2023 at 19:20 Last Updated: October 07, 2023 at 19:20 |
PW176156View Pathway |
Trilaciclib Predicted Metabolism Pathway newHomo sapiens
Metabolites of Trilaciclib are predicted with biotransformer.
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Creator: Omolola Created On: November 29, 2023 at 14:23 Last Updated: November 29, 2023 at 14:23 |
PW145197View Pathway |
drug action
Trilostane Drug Metabolism Action PathwayHomo sapiens
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Creator: Ray Kruger Created On: October 07, 2023 at 15:17 Last Updated: October 07, 2023 at 15:17 |
PW145969View Pathway |
drug action
Trimebutine Drug Metabolism Action PathwayHomo sapiens
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Creator: Ray Kruger Created On: October 07, 2023 at 17:05 Last Updated: October 07, 2023 at 17:05 |
PW127931View Pathway |
drug action
Trimebutine M3 Receptor Intestine Relaxation Action PathwayHomo sapiens
Trimebutine is a spasmolytic agent used for the symptomatic treatment of irritable bowel syndrome (IBS) and treatment of postoperative paralytic ileus following abdominal surgery. Trimebutine is a spasmolytic agent that regulates intestinal and colonic motility and relieves abdominal pain with antimuscarinic and weak mu opioid agonist effects. It is marketed for the treatment of irritable bowel syndrome (IBS) and lower gastrointestinal tract motility disorders, with IBS being one of the most common multifactorial GI disorders. It is used to restore normal bowel function and is commonly present in pharmaceutical mixtures as trimebutine maleate salt form. At high concentrations, trimebutine is shown to inhibit the extracellular Ca2+ influx in the smooth muscle cells through voltage dependent L-type Ca2+ channels and further Ca2+ release from intracellular Ca2+ stores. Trimebutine is suggested to bind to the inactivated state of the calcium channel with high affinity. Reduced calcium influx attenuates membrane depolarization and decrease colon peristalsis. It also inhibits outward K+ currents in response to membrane depolarization of the GI smooth muscle cells at resting conditions through inhibition of delayed rectifier K+ channels and Ca2+ dependent K+ channels, which results in induced muscle contractions. Trimebutine binds to mu opioid receptors with more selectivity compared to delta or kappa opioid receptors but with lower affinity than their natural ligands. Its metabolites (N-monodesmethyl-trimebutine or nor-trimebutine), are also shown to bind to opoid receptors on brain membranes and myenteric synaptosomes. Possible side effects of using trimebutine may include dry mouth, heartburn, nausea, and drowsiness.
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Creator: Hayley Created On: June 20, 2023 at 13:08 Last Updated: June 20, 2023 at 13:08 |
PW128442View Pathway |
drug action
Trimebutine Opioid Action PathwayHomo sapiens
Trimebutine is a spasmolytic agent that regulates intestinal and colonic motility and relieves abdominal pain. It has a dual function that stimulates or inhibits spontaneous contractions depending on the concentration and prior contractile activity. Trimebutine is also an antagonist of muscarinic acetylcholine receptors, further inhibiting the contraction of intestine smooth muscles.
Trimebutine is taken orally and travels to the myenteric plexus, which is a plexus of neurons that is located between the longitudinal and circular muscle layers of the intestine. Here it activates the mu-opioid receptors which is coupled with G-protein receptors. Binding of Trimebutine stimulates the exchange of GTP for GDP on the G-protein complex. The G-protein system inhibits adenylate cyclase which prevents ATP from being synthesized into cAMP which causes a decrease in intracellular cAMP. The activated G-proteins also close N-type voltage-operated calcium channels which prevents calcium from entering the neuron, and it opens calcium-dependent inwardly rectifying potassium channels which causes sodium to leave the neuron. This results in hyperpolarization and reduced neuronal excitability. Subsequently this prevents acetylcholine and other excitatory neurons from being released into the synapse. The low concentration of acetylcholine means it cannot activate muscarinic acetylcholine (M2 and M3) receptors located on the circular muscles of the instestine. Muscarinic acetylcholine receptors M3 are coupled to the Gq signaling cascade. The activation of this leads to the acitvation of phospholipase C, which converts Phosphatidylinositol (3,4,5)-trisphosphate to inositol (3,4,5)-trisphosphate (IP3) and diacylglycerol (DAG). IP3 activates IP3 receptors on the sarcoplasmic reticulum leading to the release of stored calcium into the cytosol. DAG activates protein kinase C (PKC). One of the downstream effects of PKC include activation of calcium channels on the membrane, leading to influx of calcium ions into the cytosol. Both IP3 and DAG increase cytosolic levels of calcium which then binds to calmodulin to create a calcium-calmodulin complex. Muscle contraction and relaxation are controlled by the enzymes myosin kinase and myosin phosphatase. Myosin kinase phosphorylates myosin light chain, leading to interaction between actin and myosin, producing muscle contraction. The calcium-calmodulin activates myosin kinase, leading to increased phosphorylation of myosin light chain and more muscle contraction. With acetylcholine in low concentrations, myosin light chain kinase is activated less which means contraction of the muscle occurs less often. Nitric oxide is synthesized in the epithelial cells as well as many other places near the intestine. It is lipid soluble so it can enter the myocyte and activate guanalyl cyclase which catalyzes GTP into cGMP. CGMP activates Myosin light chain phosphatase which dephosphorylates the phosphorylated myosin light chain, preventing interaction with actin, producing muscle relaxation. This keeps the myocyte relaxed for longer and slows the cyclic muscle contractions caused by action potential in the cyclic myocytes of the intestine. This keeps the substances in the intestine for longer, allowing the intestine to absorb more water from the substances.This also suppresses the gastrocolic reflex.
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Creator: Ray Kruger Created On: August 28, 2023 at 23:01 Last Updated: August 28, 2023 at 23:01 |
PW145950View Pathway |
drug action
Trimetazidine Drug Metabolism Action PathwayHomo sapiens
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Creator: Ray Kruger Created On: October 07, 2023 at 17:02 Last Updated: October 07, 2023 at 17:02 |
PW127933View Pathway |
drug action
Trimethadione Action PathwayHomo sapiens
Trimethadione is an anticonvulsant agent indicated for the control of treatment-refractory petit mal seizures. An anticonvulsant effective in absence seizures, but generally reserved for refractory cases because of its toxicity. Paramethadione and trimethadione are anticonvulsants indicated in the control of absence (petit mal) seizures that are refractory to treatment with other medications. Dione anticonvulsants are used in the treatment of epilepsy. They act on the central nervous system (CNS) to reduce the number of seizures. Dione anticonvulsants reduce T-type calcium currents in thalamic neurons, including thalamic relay neurons. It does so via the inhibition of voltage dependent T-type calcium channels. This raises the threshold for repetitive activity in the thalamus, and inhibits corticothalamic transmission. Thus, the abnormal thalamocortical rhythmicity, which is thought to underlie the 3-Hz spike-and-wave discharge seen on electroencephalogram(EEG) with absence seizures, is dampened. GABA release is inhibited due to mutations of the SCN1A, SCN1B gene causing enhanced reuptake. Possible side effects of using trimethadione may include tiredness, changes in weight, hiccups, and headache.
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Creator: Hayley Created On: June 20, 2023 at 14:03 Last Updated: June 20, 2023 at 14:03 |