50-53-3 ZPEIMTDSQAKGNT-UHFFFAOYSA-N ZPEIMTDSQAKGNT-UHFFFAOYSA-N Chlorpromazine CPZ 10H-Phenothiazine-10-propanamine, 2-chloro-N,N-dimethyl- 2-Chloro-10-[3-(dimethylamino)propyl]phenothiazine 2-Chloro-10[3'-(dimethylamino)propyl]phenothiazine 2-Chloropromazine Aminazin Aminazine Ampliactil Amplictil Chlordelazin Chlorderazin Chlorpromados Chlor-Promanyl Chlorpromazin Chlropromados clorpromazinio Contomin Elmarin Fenactil Fenaktyl Fraction AB Largactilothiazine Largactyl Megaphen Noiafren Novomazina NSC 167745 NSC 226514 Phenactyl Phenothiazine, 2-chloro-10-[3-(dimethylamino)propyl]- Promactil Promazil Propaphenin Sanopron Sedatil Thorazin Thorazine Wintermin DTXSID0022808 52-53-9 SGTNSNPWRIOYBX-UHFFFAOYNA-N SGTNSNPWRIOYBX-UHFFFAOYSA-N (+/-)-Verapamil Benzeneacetonitrile, α-[3-[[2-(3,4-dimethoxyphenyl)ethyl]methylamino]propyl]-3,4-dimethoxy-α-(1-methylethyl)- (.+-.)-Verapamil 5-[(3,4-Dimethoxyphenethyl)methylamino]-2-(3,4-dimethoxy phenyl)-2-isopropylvaleronitrile dl-Verapamil Iproveratril NSC 272306NA R,S-Verapamil Valeronitrile, 5-[(3,4-dimethoxyphenethyl)methylamino]-2-(3,4-dimethoxyphenyl)-2-isopropyl- verapamilo α-[3-[[2-(3,4-Dimethoxyphenyl)ethyl]methylamino]propyl]-3,4-dimethoxy-α-(1-methylethyl)benzeneacetonitrile DTXSID9041152 1951-25-3 IYIKLHRQXLHMJQ-UHFFFAOYSA-N IYIKLHRQXLHMJQ-UHFFFAOYSA-N Amiodarone Methanone, (2-butyl-3-benzofuranyl)[4-[2-(diethylamino)ethoxy]-3,5-diiodophenyl]- 2-Butyl-3-[3,5-diiodo-4-(2-diethylaminoethoxy)benzoyl]benzofuran 2-Butyl-3-benzofuranyl p-[(2-diethylamino)ethoxy]-m,m-diiodophenyl ketone 2-n-Butyl-3',5'-diiodo-4'-N-diethylaminoethoxy-3-benzoylbenzofuran Amidorone Amiodaron amiodarona Ancaron Ketone, 2-butyl-3-benzofuranyl 4-[2-(diethylamino)ethoxy]-3,5-diiodophenyl Sedacoron Sedacorone DTXSID7022592 PR:Q12809 PR potassium voltage-gated channel subfamily H member 2 (human) GO:0001508 GO action potential NBO:0000371 NBO aquatic locomotion NBO:0000079 NBO feeding behavior GO:0002120 GO predatory behavior VT:0005372 VT life span trait GO:0019870 GO potassium channel inhibitor activity 2 WIKI decreased 1 WIKI increased Chlorpromazine 2016-11-29T18:42:27 2016-11-29T18:42:27 Verapamil 2016-11-29T18:42:27 2016-11-29T18:42:27 Amiodarone 2016-11-29T18:42:27 2016-11-29T18:42:27 8090 NCBI medaka 52641 NCBI Gammarus pulex 6087 NCBI Hydra attenuata Decreased, Sodium conductance 1 Cellular <p>The quick rise and fall of an electrical membrane potential of a cell, known as an action potential, is either diminished or eliminated. </p> <p>Action potentials are found throughout multicellular organisms (plants, invertebrates, and vertebrates). Sponges are multicellular eukaryotes that do not transmit action potentials. </p> CL:0000255 CL eukaryotic cell AOPWiki 2016-11-29T18:41:25 2017-09-16T10:15:49 Reduced, swimming speed Individual <p><em> The swimming speed may be measured by the use of an aquatic tunnel, wherein the researcher controls the speed of the water flow (see Tierney, 2001), or by using video equipment to record the distance the organism swims within a period of time (e.g., Kavitha and Rao, 2007). </em> </p> High High Moderate <p><br /> </p><p>De Lange, H.J., Noordoven, W., Murk, A.J., Lürling, M., and Peeters, E.T.H.M. 2006. Behavioural responses of Gammarus pulex (Crustacea, Amphipoda) to low concentrations of pharmaceuticals. Aquatic toxicology 78:209-216. </p><p>Kavitha, P. and Venkateswara Rao, J. 2007. Oxidative stress and locomotor behaviour response as biomarkers for assessing recovery status of mosquito fish, Gambusia affinis after lethal effect of an organophosphate pesticide, monocrotophos. Pesticide Biochemistry and Physiology 87:182-188. </p><p>Nassef, M., Kim, S.G., Seki, M., Kang, I.J., Hano, T., Shimasaki, Y., and Oshima, Y. 2010. In ovo nanoinjection of triclosan, diclofenac and carbamazepine affects embryonic development of medaka fish (Oryzias latipes). Chemosphere 79:966-973. </p><p>Quinn, B., Gagné, F., and Blaise, C. 2008. An investigation into the acute and chronic toxicity of eleven pharmaceuticals (and their solvents) found in wastewater effluent on the cnidarian, Hydra attenuata. Science of The Total Environment 389:306-314. </p><p>Tierney, K.B. 2011. Swimming Performance Assessment in Fishes. Journal of Visualized Experiments&#160;: JoVE 2572. </p> AOPWiki 2016-11-29T18:41:25 2016-11-29T19:16:30 Reduced, feeding 1 Individual <p><em> Depending upon the organism and situation (lab or field), feeding rates may be determined by video (e.g., Nassef et al., 2010), fecal egestion (e.g., Bernot et al., 2005), or stomach contents (review by Cortes 1997). </em> </p> <p>Bernot, R.J., Kennedy, E.E., and Lamberti, G.A. 2005. Effects of ionic liquids on the survival, movement, and feeding behavior of the freshwater snail, Physa acuta. Environmental Toxicology and Chemistry 24:1759-1765. </p><p>Cortés, E. 1997. A critical review of methods of studying fish feeding based on analysis of stomach contents: application to elasmobranch fishes. Canadian Journal of Fisheries and Aquatic Sciences 54:726-738. </p><p>Nassef, M., Matsumoto, S., Seki, M., Khalil, F., Kang, I.J., Shimasaki, Y., Oshima, Y., and Honjo, T. 2010b. Acute effects of triclosan, diclofenac and carbamazepine on feeding performance of Japanese medaka fish (Oryzias latipes). Chemosphere 80:1095-1100. </p> AOPWiki 2016-11-29T18:41:25 2016-11-29T19:16:34 Increased, predation Population AOPWiki 2016-11-29T18:41:25 2016-12-03T16:37:50 Reduced, survival Population AOPWiki 2016-11-29T18:41:25 2016-12-03T16:37:50 Inhibition, Ether-a-go-go (ERG) voltage-gated potassium channel Molecular <p>In cardiomyocytes, electical depolarization occurs upon the opening of voltage-gated sodium channels (Nav1.5) and the rapid influx of sodium ions. This influx causes the upstroke of the action potential (phase 0 in a human EKG). NaV channels turn off rapidly, but the depolarization causes Ca and K channels to open. Calcium channels (Cav1.2) open and allow maintenance of depolarization. Ca2+ entry also triggers contraction of the heart muscle. Repolarization begins as potassium channels open and allow K+ out of cell, balancing out the Ca2+ influx to create the plateau of the action potential (phase 2). Potassium channels terminate the action potential and return the cell to rest (phases 3 and 4). The ether a go-go gene (ERG;KCNH2) encodes for one of the ion channel proteins (the 'rapid' delayed rectifier current (IKr)) that conducts potassium (K+) ions out of the muscle cells. This current is critical in correctly timing the return to the resting state (repolarization) of the cell membrane during the cardiac action potential (Sanguinetti and Tristani-Firouzi, 2006). In other species,such as zebrafish, other ion channels may be absent (Alday et al., 2014), but the ERG channel is likely highly conserved. </p><p>In humans, the ERG potassium channel's pore is composed of 4 identical alpha subunits. Each subunit consists of 6 transmembrane alpha helices, numbered S1-S6, a pore helix situated between S5 and S6, and cytoplasmically located N- and C-termini. Arginine or lysine amino acids present in the S4 helix likely acts as the voltage-sensitive sensor. Between the S5 and S6 helices, there is an extracellular loop (known as 'the turret') and 'the pore loop', which begins and ends extracellularly but loops into the plasma membrane; the four subunit pore loops form the selectivity filter inside the pore. </p><p>The relatively large inner vestibule of the ERG channel permits binding of many pharmaceutical agents of diverse structure and function. The more common drugs which can result in ERG block include antiarrhythmics (especially Class 1A and Class III), anti-psychotic agents, and certain antibiotics (including quinolones and macrolides). Binding of the ERG channel and subsequent inhibition of the Ikr can result in prolonged QT syndrome, Torsade de Points or bradycardia. </p> <p><em> Generally, inhibition is mmeasured using patch clamp electrophysiology. There is also a commercially available hERG fluorescence polarization kit. ToxCast assay NVS_IC_hKhERGCh also measures human ERG (hERG) inhibition. </em> </p> <p>ERG mRNA has been identified in the hearts of guinea pig, rabbit, human, dog, and rat species. In rat, erg transcript was also found in the brain, retina, thymus, adrenal gland, skeletal muscle, lung, and cornea. In isolated rat ventricular myocytes, an E-4031–sensitive current was observed, which is consistent with the presence of IKr (Wymore et al., 1997). </p> <p>Sanguinetti, M. C. and M. Tristani-Firouzi (2006). "hERG potassium channels and cardiac arrhythmia." Nature 440(7083): 463-469. </p><p>Wymore, R. S., et al. (1997). "Tissue and Species Distribution of mRNA for the ikr-like K+ Channel, ERG." Circ Res 80(2): 261-268. </p> AOPWiki 2016-11-29T18:41:25 2016-12-03T16:33:27 #<Reference::ActiveRecord_Associations_CollectionProxy:0x00007b42e98b94d8> AOPWiki 2016-11-29T18:41:34 2016-12-03T16:37:58 #<Reference::ActiveRecord_Associations_CollectionProxy:0x00007b42e98e2d60> AOPWiki 2016-11-29T18:41:34 2016-12-03T16:37:58 #<Reference::ActiveRecord_Associations_CollectionProxy:0x00007b42e9969888> AOPWiki 2016-11-29T18:41:34 2016-12-03T16:37:58 #<Reference::ActiveRecord_Associations_CollectionProxy:0x00007b42e99a0900> AOPWiki 2016-11-29T18:41:34 2016-12-03T16:37:58 #<Reference::ActiveRecord_Associations_CollectionProxy:0x00007b42e9a04d10> AOPWiki 2016-11-29T18:41:34 2016-12-03T16:37:58 #<Reference::ActiveRecord_Associations_CollectionProxy:0x00007b42e9a462b0> AOPWiki 2016-11-29T18:41:34 2016-12-03T16:37:58 ether-a-go-go (ERG) inhibition Brendan Ferreri-Hanberry <p>Kellie Fay</p> BY-SA 1.29 1.0 adjacent Not Specified High adjacent Not Specified High non-adjacent Not Specified Low non-adjacent Not Specified Not Specified non-adjacent Not Specified Not Specified non-adjacent Not Specified Not Specified <p>This AOP is largely based on biological plausibility and a few studies in aquatic species exposed to ERG or similar channel blockers. It should be considered speculative and untested.</p> AOPWiki 2016-11-29T18:41:16 2023-09-25T16:26:49