PathWhiz

PathWhiz ID	Pathway	Meta Data
PW126587 View Pathway	drug action Clonazepam Action Pathway Homo sapiens Clonazepam is a long-acting benzodiazepine with intermediate onset commonly used to treat panic disorders, severe anxiety, and seizures. Clonazepam ballosterically binds on the benzodiazepine receptors in the post-synaptic GABA-A ligand-gated chloride channel in different sites of the central nervous system (CNS). This binding will result in an increase on the GABA inhibitory effects which is translated as an increase in the flow of chloride ions into the cell causing hyperpolarization and stabilization of the cellular plasma membrane. Benzodiazepine receptor associated GABA(a) receptors exist both peripherally and in the CNS, this activity consequently facilitates various effects like sedation, hypnosis, skeletal muscle relaxation, anticonvulsant activity, and anxiolytic action. In particular, when out of the ordinary rapid and repetitive electrical signals are released in the CNS, it is proposed that the brain can become over-stimulated and ordinary functions are disrupted - resulting in seizure activity. By enhancing the neuro-inhibitory activity of GABA, it is believed that clonazepam can facilitate in decreasing any excessive electrical nerve activity in the CNS that might be contributing to seizures. Concurrently, it is also believed that clonazepam's actions in enhancing GABA effects may inhibit neuronal activity proposed to occur in amygdala-centered fear circuits - therefore assisting in the management of anxiety or panic BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: Karxena Harford Created On: January 18, 2022 at 23:09 Last Updated: January 18, 2022 at 23:09
PW145160 View Pathway	drug action Clonazepam Drug Metabolism Action Pathway Homo sapiens BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: Ray Kruger Created On: October 07, 2023 at 15:12 Last Updated: October 07, 2023 at 15:12
PW144692 View Pathway	drug action Clonidine Drug Metabolism Action Pathway Homo sapiens BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: Ray Kruger Created On: October 07, 2023 at 14:14 Last Updated: October 07, 2023 at 14:14
PW126023 View Pathway	drug action Clonidine Mechanism of Action Pathway Homo sapiens Clonidine is an alpha 2 adrenergic agonist that is used to treat a variety of conditions and diseases like hypertension, ADHD, Tourette's syndrome or human growth hormone deficiency. Alpha 2 adrenergic receptors exist on the presynaptic neuron membrane and act as a negative feedback mechanism to stop the release of neurotransmitters like norepinephrine from being released. Norepinephrine released binds to alpha 1 and beta 1 adrenergic receptors on muscle tissues or post synaptic neurons to elicit different g-protein signalling cascades with can lead to increased calcium release from cell storage. Increased calcium release promotes muscle contraction. By clonidine inhibiting the release of norepinephrine through negative feedback, less is release and therefore less muscle contraction is elicited. In cardiac muscle, less norepinephrine allows arteries to relax lowering blood pressure. Clonidine is taken orally or transdermally and is absorbed in the bloodstream where is can travel to the brain to affect the presynaptic neurons there. Clonidine reachs it's max concentration after 60-90 minutes after oral ingestion and has varying bioavailability from 55-87%. Less than 50% of clonidine is metabolized to 4-hydroxyclonidine and excreted in urine, with 50% of the dose being excreted unchanged typically. Alcohol consumption with clonidine should be avoided but food consumption is fine as it does not alter absorption. Overdose of clonidine can lead to hypotension, bradycardia, hypothermia and/or weakness. BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: Kristen Yee Created On: May 23, 2021 at 14:25 Last Updated: May 23, 2021 at 14:25
PW176010 View Pathway	metabolic Clonidine Predicted Metabolism Pathway new Homo sapiens Metabolites of Clonidine are predicted with biotransformer. BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: Omolola Created On: November 29, 2023 at 13:12 Last Updated: November 29, 2023 at 13:12
PW122428 View Pathway	drug action Clopidogrel Action Homo sapiens Clopidogrel, marketed as Plavix, is an antiplatelet drug that targets the P2Y12 receptor of platelets. Clopidogrel is taken orally as a prodrug, and must be metabolically activated before it can be effective. It first enters the liver and enters the endoplasmic reticulum where it is metabolized to form the active metabolite. First, it is catalyzed by cytochromes P450 2C19, 2B6 and 1A2 into 2-oxoclopidogrel. Secondly, it is processed by cytochromes P450 2B6, 2C9, 2C19, 3A4, 3A5, and serum paraoxonase/arylesterase 1 into the active metabolite of clopidogrel. The active metabolite of clopidogrel then enters the blood stream, where it binds irreversibly to the P2Y purinoreceptor 12 on the surface of platelet cells, preventing ADP from binding to and activating it. Clopidogrel prevents the activation of the Gi protein associated with the P2Y12 receptor from inactivating adenylate cyclase in the platelet, leading to a buildup of cAMP. This cAMP then activates calcium efflux pumps, preventing calcium buildup in the platelet, which would cause activation, and later, aggregation. BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: Eponine Oler Created On: April 08, 2019 at 15:48 Last Updated: April 08, 2019 at 15:48
PW000286 View Pathway	drug action Clopidogrel Action Pathway Homo sapiens Clopidogrel, marketed as Plavix, is an antiplatelet drug that targets the P2Y12 receptor of platelets. Clopidogrel is taken orally as a prodrug, and must be metabolically activated before it can be effective. It first enters the liver and enters the endoplasmic reticulum where it is metabolized to form the active metabolite. First, it is catalyzed by cytochromes P450 2C19, 2B6 and 1A2 into 2-oxoclopidogrel. Secondly, it is processed by cytochromes P450 2B6, 2C9, 2C19, 3A4, 3A5, and serum paraoxonase/arylesterase 1 into the active metabolite of clopidogrel. The active metabolite of clopidogrel then enters the blood stream, where it binds irreversibly to the P2Y purinoreceptor 12 on the surface of platelet cells, preventing ADP from binding to and activating it. Clopidogrel prevents the activation of the Gi protein associated with the P2Y12 receptor from inactivating adenylate cyclase in the platelet, leading to a buildup of cAMP. This cAMP then activates calcium efflux pumps, preventing calcium buildup in the platelet, which would cause activation, and later, aggregation. BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: WishartLab Created On: August 22, 2013 at 10:45 Last Updated: August 22, 2013 at 10:45
PW128059 View Pathway	drug action Clopidogrel Action Pathway (new) Homo sapiens Clopidogrel, marketed as Plavix, is an antiplatelet drug that targets the P2Y12 receptor of platelets. Clopidogrel is taken orally as a prodrug, and must be metabolically activated before it can be effective. It first enters the liver and enters the endoplasmic reticulum where it is metabolized to form the active metabolite. First, it is catalyzed by cytochromes P450 2C19, 2B6 and 1A2 into 2-oxoclopidogrel. Secondly, it is processed by cytochromes P450 2B6, 2C9, 2C19, 3A4, 3A5, and serum paraoxonase/arylesterase 1 into the active metabolite of clopidogrel. The active metabolite of clopidogrel then enters the blood stream, where it binds irreversibly to the P2Y purinoreceptor 12 on the surface of platelet cells, preventing ADP from binding to and activating it. Clopidogrel prevents the activation of the Gi protein associated with the P2Y12 receptor from inactivating adenylate cyclase in the platelet, leading to a buildup of cAMP. This cAMP then activates calcium efflux pumps, preventing calcium buildup in the platelet, which would cause activation, and later, aggregation. BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: Selena Created On: July 12, 2023 at 10:49 Last Updated: July 12, 2023 at 10:49
PW144869 View Pathway	drug action Clopidogrel Drug Metabolism Action Pathway Homo sapiens BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: Ray Kruger Created On: October 07, 2023 at 14:36 Last Updated: October 07, 2023 at 14:36
PW124569 View Pathway	metabolic Clopidogrel Metabolic Pathway Homo sapiens 85-90% of an oral dose undergoes first pass metabolism by carboxylesterase 1 in the liver to an inactive carboxylic acid metabolite. About 2% of clopidogrel is oxidized to 2-oxoclopidogrel. This conversion is 35.8% by CYP1A2, 19.4% by CYP2B6, and 44.9% by CYP2C194 though other studies suggest CYP3A4, CYP3A5, and CYP2C9 also contribute. 2-oxoclopidogrel is further metabolized to the active metabolite. This conversion is 32.9% by CYP2B6, 6.79% by CYP2C9, 20.6% by CYP2C19, and 39.8% by CYP3A4. BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: Dorsa Yahya Rayat Created On: March 02, 2021 at 17:22 Last Updated: March 02, 2021 at 17:22