PathWhiz

PathWhiz ID	Pathway	Meta Data
PW000401 View Pathway	drug action Cocaine Action Pathway Homo sapiens Cocaine exerts its local anaesthetic effect by blocking voltage-gated sodium channels in peripheral neurons. Cocaine diffuses across the neuronal plasma membrane in its uncharged base form. Once inside the cytoplasm, it is protonated and this protonated form enters and blocks the pore of the voltage-gated sodium channel from the cytoplasmic side. For this to happen, the sodium channel must first become active so that so that gating mechanism is in the open state. Therefore cocaine preferentially inhibits neurons that are actively firing. 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
PW124084 View Pathway	drug action Cocaine Action Pathway New Homo sapiens BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: Nitya Khetarpal Created On: August 16, 2020 at 23:43 Last Updated: August 16, 2020 at 23:43
PW126801 View Pathway	drug action Cocaine Analgesic Action Pathway Homo sapiens Cocaine is a local anesthesia and vasoconstrictor that is clinically used during diagnostic proceedures or during surgery in or through the nasal cavity. It comes in drugs called Goprelto and Numbrino which comes as a nasal spray. In these clinical drugs it takes the form of cocaine hydrochloride. The illicit drug has the same effects. Primarily it acts on sensory neurons in the nasal cavity by inhibiting the sodium channels. Stimulation from touch, pressure, stretch, or pain causes sodium channels on sensory receptors to open. Cocaine inhibits those channels, preventing the sensory receptor from depolarizing and triggering an action potential. The different types of sensory neurons it inhibits are mechanoreceptors(pressure, vibrations, and texture), thermoreceptors (temperature), and nociceptors (pain). The prevention of depolarization and action potential in these neurons causes an anesthetic effect in the nasal cavity. BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: Ray Kruger Created On: March 30, 2022 at 13:45 Last Updated: March 30, 2022 at 13:45
PW128143 View Pathway	drug action Cocaine Dopamine-reuptake Inhibitor Action Pathway Homo sapiens Cocaine is a local anesthesia and vasoconstrictor that is clinically used during diagnostic proceedures or during surgery in or through the nasal cavity. It comes in drugs called Goprelto and Numbrino which comes as a nasal spray. In these clinical drugs it takes the form of cocaine hydrochloride. The illicit drug has the same effects. It primarily acts on sensory neurons in the nasal cavity, but also inhibits dopamine, serotonin, and norepinephrine re-uptake channels. This inibition leads to an accumulation in the synapse of these neurotransmitters. For dopamine this leads to activation of dopamine receptors, especially the D2 dopamine receptor which has been implicated in the cause of addiction through the reward pathway. D2 receptors inhibit adenylate cyclase which leads to a lower concentration of cAMP which lowers neuronal excitability. Other dopamine receptors also have an effect on addiction,, especially the D1 dopamine receptor. The exact mechanisms in which D2 receptors cause addiction is unknown. D1 dopamine receptors also have an effect on addiction. They are Gs coupled and activated adenylate cyclase rather than inhibit. D1-D2 dopamine receptor heteromers have also been found to effect addiction, although they have not been researched enough to understand how. BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: Ray Kruger Created On: July 24, 2023 at 15:47 Last Updated: July 24, 2023 at 15:47
PW124081 View Pathway	drug action Cocaine Drug Action Action Pathway (New) Homo sapiens BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: Nitya Khetarpal Created On: August 15, 2020 at 19:31 Last Updated: August 15, 2020 at 19:31
PW124082 View Pathway	drug action Cocaine Drug Action Action Pathway (New) -- DISCARDED Homo sapiens BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: Nitya Khetarpal Created On: August 15, 2020 at 19:43 Last Updated: August 15, 2020 at 19:43
PW145008 View Pathway	drug action Cocaine Drug Metabolism Action Pathway Homo sapiens BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: Ray Kruger Created On: October 07, 2023 at 14:54 Last Updated: October 07, 2023 at 14:54
PW126809 View Pathway	metabolic Cocaine metabolism Homo sapiens Cocaine is a local anaesthetic used for diagnostic procedures or surgery on or through the nasal cavity. It is administered as a spray in the nose where it enters the blood vessels of the nose and travels through the body. When taken illicitly it is snorted through the nose and enters through the same blood vessels. Cocaine is metabolized in hepatic liver cells. Cocaine diffuses through the liver membrane. On the endoplasmic reticulum membrane it is metabolized by cytochrome P450 3A4 into norcocaine. It is also predicted by biotransformer to metabolize by cytochrome P450 1A2 into benzoylecgonine. Both of these metabolites are inactive and the main metabolite when cocaine is taken on its own. When cocaine is taken with alcohol however, it metabolizes into the active metabolite cocaethylene by the hepatic enzyme carboxylesterase in the endoplasmic reticulum lumen. Norcocaine, benzoylecogonine, and cocaethylene all diffuse through the hepatic cell membrane into the blood where they travel to the kidney and are excreted renally. However, cocaethylene is an active metabolite that is much more toxic than cocaine and has a higher affinity for dopamine re-uptake receptors, and therefore will activate similar pathways to cocaine. It takes much longer for it to be excreted renally than cocaine. Cocaethylene is often fatal. BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: Ray Kruger Created On: March 31, 2022 at 15:40 Last Updated: March 31, 2022 at 15:40
PW128144 View Pathway	drug action Cocaine Norepinephrine Reuptake Inhibitor Action Pathway Homo sapiens Cocaine is a local anesthesia and vasoconstrictor that is clinically used during diagnostic proceedures or during surgery in or through the nasal cavity. It comes in drugs called Goprelto and Numbrino which comes as a nasal spray. In these clinical drugs it takes the form of cocaine hydrochloride. The illicit drug has the same effects. It primarily acts on sensory neurons in the nasal cavity, but also inhibits dopamine, serotonin, and norepinephrine re-uptake channels. Cocaine inhibits the sodium-dependent noradrenaline channel which causes norepinephrine to accumulate in the synapse. The high concentration of norepinephrine readily activates both alpha adrenergic receptors in the smooth muscles of blood vessels. This, through the Gq signalling cascade, leads to vasoconstriction of blood vessels especially in the nose. This also causes higher heart rate and higher blood pressure, due to vasoconstriction, in the rest of the body as seen in the norepinephrine subpathway. BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: Ray Kruger Created On: July 24, 2023 at 15:48 Last Updated: July 24, 2023 at 15:48
PW145504 View Pathway	drug action Cocarboxylase Drug Metabolism Action Pathway Homo sapiens BioPAX SVG SBGN SBML PWML All files (.zip)	Creator: Ray Kruger Created On: October 07, 2023 at 15:57 Last Updated: October 07, 2023 at 15:57