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Pathway Description
Cocaine Analgesic Action Pathway
Homo sapiens
Category:
Metabolite Pathway
Sub-Category:
Drug Action
Created: 2022-03-30
Last Updated: 2023-10-25
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.
References
Cocaine Analgesic Pathway References
George F. Koob, Dopamine, addiction and reward, Seminars in Neuroscience, Volume 4, Issue 2, 1992, Pages 139-148, ISSN 1044-5765, https://doi.org/10.1016/1044-5765(92)90012-Q.
McClung CA, Sidiropoulou K, Vitaterna M, Takahashi JS, White FJ, Cooper DC, Nestler EJ: Regulation of dopaminergic transmission and cocaine reward by the Clock gene. Proc Natl Acad Sci U S A. 2005 Jun 28;102(26):9377-81. doi: 10.1073/pnas.0503584102. Epub 2005 Jun 20.
Pubmed: 15967985
Crumb WJ Jr, Clarkson CW: Characterization of cocaine-induced block of cardiac sodium channels. Biophys J. 1990 Mar;57(3):589-99. doi: 10.1016/S0006-3495(90)82574-1.
Pubmed: 2155033
Wright SN, Wang SY, Xiao YF, Wang GK: State-dependent cocaine block of sodium channel isoforms, chimeras, and channels coexpressed with the beta1 subunit. Biophys J. 1999 Jan;76(1 Pt 1):233-45. doi: 10.1016/S0006-3495(99)77192-4.
Pubmed: 9876137
Rabert DK, Koch BD, Ilnicka M, Obernolte RA, Naylor SL, Herman RC, Eglen RM, Hunter JC, Sangameswaran L: A tetrodotoxin-resistant voltage-gated sodium channel from human dorsal root ganglia, hPN3/SCN10A. Pain. 1998 Nov;78(2):107-14. doi: 10.1016/s0304-3959(98)00120-1.
Pubmed: 9839820
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Pubmed: 16641997
Varela I, Tarpey P, Raine K, Huang D, Ong CK, Stephens P, Davies H, Jones D, Lin ML, Teague J, Bignell G, Butler A, Cho J, Dalgliesh GL, Galappaththige D, Greenman C, Hardy C, Jia M, Latimer C, Lau KW, Marshall J, McLaren S, Menzies A, Mudie L, Stebbings L, Largaespada DA, Wessels LF, Richard S, Kahnoski RJ, Anema J, Tuveson DA, Perez-Mancera PA, Mustonen V, Fischer A, Adams DJ, Rust A, Chan-on W, Subimerb C, Dykema K, Furge K, Campbell PJ, Teh BT, Stratton MR, Futreal PA: Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma. Nature. 2011 Jan 27;469(7331):539-42. doi: 10.1038/nature09639. Epub 2011 Jan 19.
Pubmed: 21248752
Makita N, Sloan-Brown K, Weghuis DO, Ropers HH, George AL Jr: Genomic organization and chromosomal assignment of the human voltage-gated Na+ channel beta 1 subunit gene (SCN1B). Genomics. 1994 Oct;23(3):628-34. doi: 10.1006/geno.1994.1551.
Pubmed: 7851891
Patino GA, Claes LR, Lopez-Santiago LF, Slat EA, Dondeti RS, Chen C, O'Malley HA, Gray CB, Miyazaki H, Nukina N, Oyama F, De Jonghe P, Isom LL: A functional null mutation of SCN1B in a patient with Dravet syndrome. J Neurosci. 2009 Aug 26;29(34):10764-78. doi: 10.1523/JNEUROSCI.2475-09.2009.
Pubmed: 19710327
Baroni D, Picco C, Moran O: A mutation of SCN1B associated with GEFS+ causes functional and maturation defects of the voltage-dependent sodium channel. Hum Mutat. 2018 Oct;39(10):1402-1415. doi: 10.1002/humu.23589. Epub 2018 Jul 30.
Pubmed: 29992740
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