50-53-3ZPEIMTDSQAKGNT-UHFFFAOYSA-NZPEIMTDSQAKGNT-UHFFFAOYSA-N
ChlorpromazineCPZ
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
DTXSID002280852-53-9SGTNSNPWRIOYBX-UHFFFAOYNA-NSGTNSNPWRIOYBX-UHFFFAOYSA-N
(+/-)-VerapamilBenzeneacetonitrile, 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
DTXSID90411521951-25-3IYIKLHRQXLHMJQ-UHFFFAOYSA-NIYIKLHRQXLHMJQ-UHFFFAOYSA-N
AmiodaroneMethanone, (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
DTXSID7022592PR:Q12809potassium voltage-gated channel subfamily H member 2 (human)GO:0001508action potentialNBO:0000371aquatic locomotionNBO:0000079feeding behaviorGO:0002120predatory behaviorVT:0005372life span traitGO:0019870potassium channel inhibitor activity2decreased1increasedChlorpromazine2016-11-29T18:42:272016-11-29T18:42:27Verapamil2016-11-29T18:42:272016-11-29T18:42:27Amiodarone2016-11-29T18:42:272016-11-29T18:42:278090medaka52641Gammarus pulex6087Hydra attenuataDecreased, Sodium conductance 1Decreased, Sodium conductance 1Cellular<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:0000255eukaryotic cell2016-11-29T18:41:252017-09-16T10:15:49Reduced, swimming speedReduced, swimming speedIndividual<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>HighHighModerate<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 : JoVE 2572.
</p>2016-11-29T18:41:252016-11-29T19:16:30Reduced, feeding 1Reduced, feeding 1Individual<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>2016-11-29T18:41:252016-11-29T19:16:34Increased, predationIncreased, predationPopulation2016-11-29T18:41:252016-12-03T16:37:50Reduced, survivalReduced, survivalPopulation2016-11-29T18:41:252016-12-03T16:37:50Inhibition, Ether-a-go-go (ERG) voltage-gated potassium channel 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>2016-11-29T18:41:252016-12-03T16:33:279ffe80ab-4e66-49c6-a7f7-dd57c9f7ac832321835a-8ef6-4e19-ab1f-0a3c26ed34972016-11-29T18:41:342016-12-03T16:37:582321835a-8ef6-4e19-ab1f-0a3c26ed3497c0c3e332-1913-4d4a-b3d1-14d9c8cecb7d2016-11-29T18:41:342016-12-03T16:37:582321835a-8ef6-4e19-ab1f-0a3c26ed34979fbd409c-55e5-4104-9f2f-b38bb40eb3362016-11-29T18:41:342016-12-03T16:37:58c0c3e332-1913-4d4a-b3d1-14d9c8cecb7d9fbd409c-55e5-4104-9f2f-b38bb40eb3362016-11-29T18:41:342016-12-03T16:37:589fbd409c-55e5-4104-9f2f-b38bb40eb33667b01a14-1428-4a74-b8d3-289bca5778162016-11-29T18:41:342016-12-03T16:37:58427256ff-9e3a-4da4-a17d-80a7df442f3a9ffe80ab-4e66-49c6-a7f7-dd57c9f7ac832016-11-29T18:41:342016-12-03T16:37:58Ether-a-go-go (ERG) voltage-gated potassium channel inhibition leading to reduced survivalether-a-go-go (ERG) inhibition<p>Kellie Fay</p>
Under Development: Contributions and Comments WelcomeUnder Development1.29adjacentNot SpecifiedHighadjacentNot SpecifiedHighnon-adjacentNot SpecifiedLownon-adjacentNot SpecifiedNot Specifiednon-adjacentNot SpecifiedNot Specifiednon-adjacentNot SpecifiedNot 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>
2016-11-29T18:41:162023-04-29T16:02:57