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Pathway Description
Isoflurophate Action Pathway (new)
Homo sapiens
Drug Action Pathway
Created: 2023-08-15
Last Updated: 2023-11-27
Isoflurophate is a cholinesterase inhibitor used to treat glaucoma, as it acts as a powerful miotic agent constricting the pupil and causing the aqueous fluid to flow out and relieve pressure. It acts by irreversibly binding to acetylcholinesterase and cholinesterase, inhibiting them from breaking down acetylcholine. Once isoflurophate binds to the enzymes it elicits parasympathomimetic effects, constricting the pupil and causing an outflow of fluid to drain out of the eye relieving the pressure caused by glaucoma. Due to irreversible binding, this damages the enzyme and can only be displaced by pralidoxime if it is administered prior to isoflurophate. If an overdose occurs some symptoms such as sweating, loss of bladder control, weakness, nausea, vomiting, diarrhea, cramps, stomach pains, shortness of breath, tight chest, wheezing, arrhythmias, fatigue or sudden salivation.
References
Isoflurophate Pathway (new) References
Gearhart JM, Jepson GW, Clewell HJ 3rd, Andersen ME, Conolly RB: Physiologically based pharmacokinetic and pharmacodynamic model for the inhibition of acetylcholinesterase by diisopropylfluorophosphate. Toxicol Appl Pharmacol. 1990 Nov;106(2):295-310. doi: 10.1016/0041-008x(90)90249-t.
Pubmed: 2256118
Hartleib J, Ruterjans H: Insights into the reaction mechanism of the diisopropyl fluorophosphatase from Loligo vulgaris by means of kinetic studies, chemical modification and site-directed mutagenesis. Biochim Biophys Acta. 2001 Apr 7;1546(2):312-24. doi: 10.1016/s0167-4838(01)00153-4.
Pubmed: 11295437
Sanchez-Fortun S, Barahona MV: Toxicity and characterization of cholinesterase-inhibition induced by diisopropyl fluorophosphate in Artemia salina larvae. Ecotoxicol Environ Saf. 2009 Mar;72(3):775-80. doi: 10.1016/j.ecoenv.2007.11.004. Epub 2008 Jan 8.
Pubmed: 18191451
Toussaint JL, Geoffroy V, Schmitt M, Werner A, Garnier JM, Simoni P, Kempf J: Human choline acetyltransferase (CHAT): partial gene sequence and potential control regions. Genomics. 1992 Feb;12(2):412-6.
Pubmed: 1339386
Kraner S, Laufenberg I, Strassburg HM, Sieb JP, Steinlein OK: Congenital myasthenic syndrome with episodic apnea in patients homozygous for a CHAT missense mutation. Arch Neurol. 2003 May;60(5):761-3. doi: 10.1001/archneur.60.5.761.
Pubmed: 12756141
Oda Y, Nakanishi I, Deguchi T: A complementary DNA for human choline acetyltransferase induces two forms of enzyme with different molecular weights in cultured cells. Brain Res Mol Brain Res. 1992 Dec;16(3-4):287-94. doi: 10.1016/0169-328x(92)90237-6.
Pubmed: 1337937
Wilson MD, Riemer C, Martindale DW, Schnupf P, Boright AP, Cheung TL, Hardy DM, Schwartz S, Scherer SW, Tsui LC, Miller W, Koop BF: Comparative analysis of the gene-dense ACHE/TFR2 region on human chromosome 7q22 with the orthologous region on mouse chromosome 5. Nucleic Acids Res. 2001 Mar 15;29(6):1352-65. doi: 10.1093/nar/29.6.1352.
Pubmed: 11239002
Soreq H, Ben-Aziz R, Prody CA, Seidman S, Gnatt A, Neville L, Lieman-Hurwitz J, Lev-Lehman E, Ginzberg D, Lipidot-Lifson Y, et al.: Molecular cloning and construction of the coding region for human acetylcholinesterase reveals a G + C-rich attenuating structure. Proc Natl Acad Sci U S A. 1990 Dec;87(24):9688-92. doi: 10.1073/pnas.87.24.9688.
Pubmed: 2263619
Karpel R, Ben Aziz-Aloya R, Sternfeld M, Ehrlich G, Ginzberg D, Tarroni P, Clementi F, Zakut H, Soreq H: Expression of three alternative acetylcholinesterase messenger RNAs in human tumor cell lines of different tissue origins. Exp Cell Res. 1994 Feb;210(2):268-77. doi: 10.1006/excr.1994.1039.
Pubmed: 8299725
Williams ME, Brust PF, Feldman DH, Patthi S, Simerson S, Maroufi A, McCue AF, Velicelebi G, Ellis SB, Harpold MM: Structure and functional expression of an omega-conotoxin-sensitive human N-type calcium channel. Science. 1992 Jul 17;257(5068):389-95. doi: 10.1126/science.1321501.
Pubmed: 1321501
Humphray SJ, Oliver K, Hunt AR, Plumb RW, Loveland JE, Howe KL, Andrews TD, Searle S, Hunt SE, Scott CE, Jones MC, Ainscough R, Almeida JP, Ambrose KD, Ashwell RI, Babbage AK, Babbage S, Bagguley CL, Bailey J, Banerjee R, Barker DJ, Barlow KF, Bates K, Beasley H, Beasley O, Bird CP, Bray-Allen S, Brown AJ, Brown JY, Burford D, Burrill W, Burton J, Carder C, Carter NP, Chapman JC, Chen Y, Clarke G, Clark SY, Clee CM, Clegg S, Collier RE, Corby N, Crosier M, Cummings AT, Davies J, Dhami P, Dunn M, Dutta I, Dyer LW, Earthrowl ME, Faulkner L, Fleming CJ, Frankish A, Frankland JA, French L, Fricker DG, Garner P, Garnett J, Ghori J, Gilbert JG, Glison C, Grafham DV, Gribble S, Griffiths C, Griffiths-Jones S, Grocock R, Guy J, Hall RE, Hammond S, Harley JL, Harrison ES, Hart EA, Heath PD, Henderson CD, Hopkins BL, Howard PJ, Howden PJ, Huckle E, Johnson C, Johnson D, Joy AA, Kay M, Keenan S, Kershaw JK, Kimberley AM, King A, Knights A, Laird GK, Langford C, Lawlor S, Leongamornlert DA, Leversha M, Lloyd C, Lloyd DM, Lovell J, Martin S, Mashreghi-Mohammadi M, Matthews L, McLaren S, McLay KE, McMurray A, Milne S, Nickerson T, Nisbett J, Nordsiek G, Pearce AV, Peck AI, Porter KM, Pandian R, Pelan S, Phillimore B, Povey S, Ramsey Y, Rand V, Scharfe M, Sehra HK, Shownkeen R, Sims SK, Skuce CD, Smith M, Steward CA, Swarbreck D, Sycamore N, Tester J, Thorpe A, Tracey A, Tromans A, Thomas DW, Wall M, Wallis JM, West AP, Whitehead SL, Willey DL, Williams SA, Wilming L, Wray PW, Young L, Ashurst JL, Coulson A, Blocker H, Durbin R, Sulston JE, Hubbard T, Jackson MJ, Bentley DR, Beck S, Rogers J, Dunham I: DNA sequence and analysis of human chromosome 9. Nature. 2004 May 27;429(6990):369-74. doi: 10.1038/nature02465.
Pubmed: 15164053
Kim DS, Jung HH, Park SH, Chin H: Isolation and characterization of the 5'-upstream region of the human N-type calcium channel alpha1B subunit gene. Chromosomal localization and promoter analysis. J Biol Chem. 1997 Feb 21;272(8):5098-104. doi: 10.1074/jbc.272.8.5098.
Pubmed: 9030575
Klugbauer N, Lacinova L, Marais E, Hobom M, Hofmann F: Molecular diversity of the calcium channel alpha2delta subunit. J Neurosci. 1999 Jan 15;19(2):684-91.
Pubmed: 9880589
Gao B, Sekido Y, Maximov A, Saad M, Forgacs E, Latif F, Wei MH, Lerman M, Lee JH, Perez-Reyes E, Bezprozvanny I, Minna JD: Functional properties of a new voltage-dependent calcium channel alpha(2)delta auxiliary subunit gene (CACNA2D2). J Biol Chem. 2000 Apr 21;275(16):12237-42. doi: 10.1074/jbc.275.16.12237.
Pubmed: 10766861
Hobom M, Dai S, Marais E, Lacinova L, Hofmann F, Klugbauer N: Neuronal distribution and functional characterization of the calcium channel alpha2delta-2 subunit. Eur J Neurosci. 2000 Apr;12(4):1217-26. doi: 10.1046/j.1460-9568.2000.01009.x.
Pubmed: 10762351
Escayg A, Jones JM, Kearney JA, Hitchcock PF, Meisler MH: Calcium channel beta 4 (CACNB4): human ortholog of the mouse epilepsy gene lethargic. Genomics. 1998 May 15;50(1):14-22. doi: 10.1006/geno.1998.5311.
Pubmed: 9628818
Escayg A, De Waard M, Lee DD, Bichet D, Wolf P, Mayer T, Johnston J, Baloh R, Sander T, Meisler MH: Coding and noncoding variation of the human calcium-channel beta4-subunit gene CACNB4 in patients with idiopathic generalized epilepsy and episodic ataxia. Am J Hum Genet. 2000 May;66(5):1531-9. doi: 10.1086/302909. Epub 2000 Apr 4.
Pubmed: 10762541
Taviaux S, Williams ME, Harpold MM, Nargeot J, Lory P: Assignment of human genes for beta 2 and beta 4 subunits of voltage-dependent Ca2+ channels to chromosomes 10p12 and 2q22-q23. Hum Genet. 1997 Aug;100(2):151-4. doi: 10.1007/pl00008704.
Pubmed: 9254841
Powers PA, Liu S, Hogan K, Gregg RG: Skeletal muscle and brain isoforms of a beta-subunit of human voltage-dependent calcium channels are encoded by a single gene. J Biol Chem. 1992 Nov 15;267(32):22967-72.
Pubmed: 1385409
Williams ME, Feldman DH, McCue AF, Brenner R, Velicelebi G, Ellis SB, Harpold MM: Structure and functional expression of alpha 1, alpha 2, and beta subunits of a novel human neuronal calcium channel subtype. Neuron. 1992 Jan;8(1):71-84. doi: 10.1016/0896-6273(92)90109-q.
Pubmed: 1309651
Collin T, Wang JJ, Nargeot J, Schwartz A: Molecular cloning of three isoforms of the L-type voltage-dependent calcium channel beta subunit from normal human heart. Circ Res. 1993 Jun;72(6):1337-44. doi: 10.1161/01.res.72.6.1337.
Pubmed: 7916667
Peralta EG, Ashkenazi A, Winslow JW, Smith DH, Ramachandran J, Capon DJ: Distinct primary structures, ligand-binding properties and tissue-specific expression of four human muscarinic acetylcholine receptors. EMBO J. 1987 Dec 20;6(13):3923-9.
Pubmed: 3443095
Bonner TI, Young AC, Brann MR, Buckley NJ: Cloning and expression of the human and rat m5 muscarinic acetylcholine receptor genes. Neuron. 1988 Jul;1(5):403-10. doi: 10.1016/0896-6273(88)90190-0.
Pubmed: 3272174
Kitano T, Liu YH, Ueda S, Saitou N: Human-specific amino acid changes found in 103 protein-coding genes. Mol Biol Evol. 2004 May;21(5):936-44. doi: 10.1093/molbev/msh100. Epub 2004 Mar 10.
Pubmed: 15014171
Van Raamsdonk CD, Bezrookove V, Green G, Bauer J, Gaugler L, O'Brien JM, Simpson EM, Barsh GS, Bastian BC: Frequent somatic mutations of GNAQ in uveal melanoma and blue naevi. Nature. 2009 Jan 29;457(7229):599-602. doi: 10.1038/nature07586. Epub 2008 Dec 10.
Pubmed: 19078957
Murali R, Wiesner T, Rosenblum MK, Bastian BC: GNAQ and GNA11 mutations in melanocytomas of the central nervous system. Acta Neuropathol. 2012 Mar;123(3):457-9. doi: 10.1007/s00401-012-0948-x. Epub 2012 Feb 4.
Pubmed: 22307269
Dong Q, Shenker A, Way J, Haddad BR, Lin K, Hughes MR, McBride OW, Spiegel AM, Battey J: Molecular cloning of human G alpha q cDNA and chromosomal localization of the G alpha q gene (GNAQ) and a processed pseudogene. Genomics. 1995 Dec 10;30(3):470-75. doi: 10.1006/geno.1995.1267.
Pubmed: 8825633
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