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Research ArticleNew Research, Disorders of the Nervous System

Large-Scale Phenotype-Based Antiepileptic Drug Screening in a Zebrafish Model of Dravet Syndrome

Matthew T. Dinday and Scott C. Baraban
eNeuro 20 August 2015, 2 (4) ENEURO.0068-15.2015; DOI: https://doi.org/10.1523/ENEURO.0068-15.2015
Matthew T. Dinday
1Department of Neurological Surgery, Epilepsy Research Laboratory, University of California San Francisco, San Francisco, California 94143
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Scott C. Baraban
1Department of Neurological Surgery, Epilepsy Research Laboratory, University of California San Francisco, San Francisco, California 94143
2Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, California 94143
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  • Figure 1.
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    Figure 1.

    Locomotion assay to identify drugs that rescue the scn1Lab mutant epilepsy phenotype. a, Schematic of the phenotype-based screening process. Chemical libraries can be coded and aliquoted in small volumes (75 µL) into individual wells containing one mutant fish. The 96-well microplate is arranged so that six fish are tested per drug; with one row of six fish maintained as an internal control (red circles) on each plate. b, Representative images for WT and scn1Lab mutant zebrafish larvae at 5 dpf. Note the morphological similarity but darker pigmentation in mutant larvae. c, Box plot of mean velocity (in millimeters per second) for two consecutive recordings of mutant larvae in embryo media. Experiments were performed by first placing the mutant larvae in embryo media and obtaining a baseline locomotion response; embryo media was then replaced with new embryo media (to mimic the procedure used for test compounds), and a second locomotion response was obtained. The percentage change in velocity from baseline (recording 1) versus experimental model (recording 2) is shown. In the box plot, the bottom and top of the box represent the 25th percentile and the 75th percentile, respectively. The line across the box represents the median value, and the vertical lines encompass the entire range of values. This plot represents normal changes in tracking activity in the absence of a drug challenge. d, Plot of locomotor seizure behavior for scn1Lab mutants at 5 dpf for the 1012 compounds tested. Threshold for inhibition of seizure activity (positive hits) was set as a reduction in mean swim velocity of ≥44%; the threshold for a proconvulsant or hyperexcitable effect was set at an increase in the mean swim velocity of ≥44% (green dashed lines).

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    Figure 2.

    Positive hits identified in the locomotion assay. a, Heat map showing the results of individual zebrafish trials (1-6) for compounds tested at a concentration of 100 µm in the locomotion-tracking assay. Raw data values for individual fish are shown within the color-coded boxes for one sample trial. Mean velocity data are shown at right for “trial 1” and “trial 2”; six fish per trial. Note: only drugs highlighted in bold type were classified as positive nontoxic hits in two independent trials and moved on to further testing. b, Representative raw locomotion data plots for six individual scn1Lab mutant larvae at baseline (top) and following the addition of a compound resulting in fatality (bottom, gemfibrozil) or hyperactivity (bottom, mepivacaine). Movement is color coded, with low-velocity movements shown in yellow, and high velocity movements shown in red.

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    Figure 3.

    Electrophysiology assay to identify drugs that rescue the scn1Lab mutant epilepsy phenotype. a, Representative field electrode recording epochs (5 min in duration) are shown for the “positive” compounds identified in the locomotion assay. All recordings were obtained with an electrode placed in the forebrain of agar-immobilized scn1Lab larvae that was previously tested in the locomotion assay. A suppression of epileptiform electrographic discharge activity was noted in mutants exposed to dimethadione. b, Bar plot showing the mean number of epileptiform events in a 10 min recording epoch for scn1Lab larvae exposed to cytarabine (N = 6), dimethadione (N = 6), theobromine (N = 6), and norfloxacin (N = 6). The mean ± SEM is shown. The fish shown were tested in the locomotion assay first. c, Bar plot showing the total distance traveled before (black bars) and after (white bars) exposure to a test compound; 10 min recording epoch and six fish per drug. The mean ± SEM is shown.

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    Figure 4.

    Evaluation of putative antiepileptic drugs in scn1Lab mutants. a, Locomotion tracking plots for scn1Lab zebrafish at baseline and following huperzine A administration. Total movement is shown for a 10 min recording epoch. b, Plot showing the change in mean velocity for three different huperzine A concentrations (blue bars). Each bar is the mean change for six fish. The threshold for a positive hit is shown as a dashed line. WT fish exposed to PTZ and huperzine A are shown in red (N = 7). c, d, Same for fenfluramine. Note that 1 mm fenfluramine was toxic, as indicated. e, Representative field recordings from scn1Lab mutant larvae at 5 dpf. Electrographic activity is shown for a 5 min recording epoch (top traces); high-resolution traces are shown below, as indicated. Note that abnormal burst discharge activity persists in scn1Lab mutants exposed to 250 µm fenfluramine. The fish shown were tested in the locomotion assay first.

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    Table 1.

    List of compounds from the PHARMAKON 1600 library used in this screen.

    ABACAVIR SULFATE
    ABAMECTIN (avermectin B1a shown)
    ACADESINE
    ACARBOSE
    ACEBUTOLOL HYDROCHLORIDE
    ACECLIDINE
    ACECLOFENAC
    ACENOCOUMAROL
    ACETAMINOPHEN
    ACETOHYDROXAMIC ACID
    ACETOPHENAZINE MALEATE
    ACETRIAZOIC ACID
    ACETYLCHOLINE CHLORIDE
    ACETYLCYSTEINE
    ACIPIMOX
    ACONITINE
    ACRIFLAVINIUM HYDROCHLORIDE
    ACRISORCIN
    ACTARIT
    ACYCLOVIR
    ADAPALENE
    ADELMIDROL
    ADENINE
    ADENOSINE
    ADENOSINE PHOSPHATE
    ADIPHENINE HYDROCHLORIDE
    AKLOMIDE
    ALAPROCLATE
    ALBENDAZOLE
    ALBUTEROL (+/-)
    ALENDRONATE SODIUM
    ALEXIDINE HYDROCHLORIDE
    ALLANTOIN
    ALLOPURINOL
    ALMOTRIPTAN
    alpha-TOCHOPHEROL
    alpha-TOCHOPHERYL ACETATE
    ALPRAZOLAM
    ALRESTATIN
    ALTHIAZIDE
    ALTRETAMINE
    ALVERINE CITRATE
    AMANTADINE HYDROCHLORIDE
    AMCINONIDE
    AMIFOSTINE
    AMIKACIN SULFATE
    AMILORIDE HYDROCHLORIDE
    AMINACRINE
    AMINOCAPROIC ACID
    AMINOGLUTETHIMIDE
    AMINOHIPPURIC ACID
    AMINOLEVULINIC ACID HYDROCHLORIDE
    AMINOSALICYLATE SODIUM
    AMITRIPTYLINE HYDROCHLORIDE
    AMLEXANOX
    AMLODIPINE BESYLATE
    AMODIAQUINE DIHYDROCHLORIDE
    AMOROLFINE HYDROCHLORIDE
    AMOXICILLIN
    AMPHOTERICIN B
    AMPICILLIN SODIUM
    AMPROLIUM
    AMSACRINE
    ANASTROZOLE
    ANCITABINE HYDROCHLORIDE
    ANETHOLE
    ANIRACETAM
    ANISINDIONE
    ANTAZOLINE PHOSPHATE
    ANTHRALIN
    ANTIPYRINE
    APOMORPHINE HYDROCHLORIDE
    APRAMYCIN
    ARGININE HYDROCHLORIDE
    ARMODAFINIL
    ARTEMETHER
    ARTEMOTIL
    ARTESUNATE
    ASCORBIC ACID
    ASPIRIN
    ATENOLOL
    ATORVASTATIN CALCIUM
    ATOVAQUONE
    ATROPINE SULFATE
    AUROTHIOGLUCOSE
    AVOBENZONE
    AZACITIDINE
    AZASERINE
    AZATADINE MALEATE
    AZATHIOPRINE
    AZELAIC ACID
    AZITHROMYCIN
    AZLOCILLIN SODIUM
    AZTREONAM
    BACAMPICILLIN HYDROCHLORIDE
    BACITRACIN
    BACLOFEN
    BALSALAZIDE DISODIUM
    BECLOMETHASONE DIPROPIONATE
    BEKANAMYCIN SULFATE
    BEMOTRIZINOL
    BENAZEPRIL HYDROCHLORIDE
    BENDROFLUMETHIAZIDE
    BENORILATE
    BENSERAZIDE HYDROCHLORIDE
    BENZALKONIUM CHLORIDE
    BENZETHONIUM CHLORIDE
    BENZOCAINE
    BENZOIC ACID
    BENZONATATE
    BENZOYL PEROXIDE
    BENZTHIAZIDE
    BENZYL ALCOHOL
    BENZYL BENZOATE
    BEPRIDIL HYDROCHLORIDE
    BERGAPTEN
    beta-CAROTENE
    BETAHISTINE HYDROCHLORIDE
    BETAINE HYDROCHLORIDE
    BETAMETHASONE
    BETAMETHASONE 17,21-DIPROPIONATE
    BETAMETHASONE VALERATE
    BETAMIPRON
    beta-NAPHTHOL
    BETAZOLE HYDROCHLORIDE
    BETHANECHOL CHLORIDE
    BEZAFIBRATE
    BICALUTAMIDE
    BIOTIN
    BISACODYL
    BISOCTRIZOLE
    BISORCIC
    BITHIONATE SODIUM
    BLEOMYCIN (bleomycin B2 shown)
    BRETYLIUM TOSYLATE
    BRINZOLAMIDE
    BROMHEXINE HYDROCHLORIDE
    BROMOCRIPTINE MESYLATE
    BROMPHENIRAMINE MALEATE
    BROXYQUINOLINE
    BUDESONIDE
    BUMETANIDE
    BUPIVACAINE HYDROCHLORIDE
    BUPROPION
    BUSULFAN
    BUTACAINE
    BUTAMBEN
    BUTOCONAZOLE
    CAFFEINE
    CAMPHOR (1R)
    CANDESARTAN
    CANDESARTAN CILEXTIL
    CANDICIDIN
    CANRENOIC ACID, POTASSIUM SALT
    CANRENONE
    CAPECITABINE
    CAPREOMYCIN SULFATE
    CAPSAICIN
    CAPTAMINE
    CAPTOPRIL
    CARBACHOL
    CARBENICILLIN DISODIUM
    CARBENOXOLONE SODIUM
    CARBETAPENTANE CITRATE
    CARBIDOPA
    CARBINOXAMINE MALEATE
    CARBOPLATIN
    CARISOPRODOL
    CARMUSTINE
    CARNITINE (dl) HYDROCHLORIDE
    CARPROFEN
    CARVEDILOL
    CEFACLOR
    CEFADROXIL
    CEFAMANDOLE NAFATE
    CEFAMANDOLE SODIUM
    CEFAZOLIN SODIUM
    CEFDINIR
    CEFEPIME HYDROCHLORIDE
    CEFMENOXIME HYDROCHLORIDE
    CEFMETAZOLE SODIUM
    CEFOPERAZONE
    CEFORANIDE
    CEFOTAXIME SODIUM
    CEFOTETAN
    CEFOXITIN SODIUM
    CEFPIRAMIDE
    CEFSULODIN SODIUM
    CEFTIBUTEN
    CEFTIOFUR HYDROCHLORIDE
    CEFTRIAXONE SODIUM TRIHYDRATE
    CEFUROXIME AXETIL
    CEFUROXIME SODIUM
    CELECOXIB
    CEPHALEXIN
    CEPHALOTHIN SODIUM
    CEPHAPIRIN SODIUM
    CEPHRADINE
    CETYLPYRIDINIUM CHLORIDE
    CHENODIOL
    CHLORAMBUCIL
    CHLORAMPHENICOL
    CHLORAMPHENICOL HEMISUCCINATE
    CHLORAMPHENICOL PALMITATE
    CHLORCYCLIZINE HYDROCHLORIDE
    CHLORHEXIDINE
    CHLOROCRESOL
    CHLOROGUANIDE HYDROCHLORIDE
    CHLOROQUINE DIPHOSPHATE
    CHLOROTHIAZIDE
    CHLOROXINE
    CHLOROXYLENOL
    CHLORPHENIRAMINE (S) MALEATE
    CHLORPROMAZINE
    CHLORPROPAMIDE
    CHLORPROTHIXENE HYDROCHLORIDE
    CHLORTETRACYCLINE HYDROCHLORIDE
    CHLORTHALIDONE
    CHLORZOXAZONE
    CHOLECALCIFEROL
    CHOLESTEROL
    CHOLINE CHLORIDE
    CICLOPIROX OLAMINE
    CILOSTAZOL
    CIMETIDINE
    CINCHOPHEN
    CINNARAZINE
    CINOXACIN
    CINTRIAMIDE
    CIPROFIBRATE
    CIPROFLOXACIN
    CISPLATIN
    CITALOPRAM HYDROBROMIDE
    CITICOLINE
    CLARITHROMYCIN
    CLAVULANATE LITHIUM
    CLEMASTINE
    CLIDINIUM BROMIDE
    CLINAFOXACIN HYDROCHLORIDE
    CLINDAMYCIN HYDROCHLORIDE
    CLIOQUINOL
    CLOBETASOL PROPIONATE
    CLOFARABINE
    CLOFIBRATE
    CLOMIPHENE CITRATE
    CLONIDINE HYDROCHLORIDE
    CLOPIDOGREL SULFATE
    CLORSULON
    CLOSANTEL
    CLOTRIMAZOLE
    CLOXACILLIN SODIUM
    CLOXYQUIN
    CLOZAPINE
    COENZYME B12
    COLCHICINE
    COLFORSIN
    COLISTIMETHATE SODIUM
    CORTISONE ACETATE
    COTININE
    CRESOL
    CROMOLYN SODIUM
    CRYOFLURANE
    CYCLAMIC ACID
    CYCLIZINE
    CYCLOBENZAPRINE HYDROCHLORIDE
    CYCLOHEXIMIDE
    CYCLOPENTOLATE HYDROCHLORIDE
    CYCLOPHOSPHAMIDE HYDRATE
    CYCLOSERINE (D)
    CYCLOSPORINE
    CYCLOTHIAZIDE
    CYPERMETHRIN
    CYPROTERONE ACETATE
    CYSTEAMINE HYDROCHLORIDE
    CYTARABINE
    DACARBAZINE
    DACTINOMYCIN
    DANAZOL
    DANTHRON
    DANTROLENE SODIUM
    DAPSONE
    DAPTOMYCIN
    DASATINIB
    DAUNORUBICIN
    DECIMEMIDE
    DEFEROXAMINE MESYLATE
    DEFLAZACORT
    DEHYDROACETIC ACID
    DEHYDROCHOLIC ACID
    DEMECLOCYCLINE HYDROCHLORIDE
    DERACOXIB
    DESIPRAMINE HYDROCHLORIDE
    DESOXYCORTICOSTERONE ACETATE
    DESVENLAFAXINE SUCCINATE
    DEXAMETHASONE
    DEXAMETHASONE ACETATE
    DEXAMETHASONE SODIUM PHOSPHATE
    DEXIBUPROFEN
    DEXLANSOPRAZOLE
    DEXPROPRANOLOL HYDROCHLORIDE
    DEXTROMETHORPHAN HYDROBROMIDE
    DIAVERIDINE
    DIBENZOTHIOPHENE
    DIBUCAINE HYDROCHLORIDE
    DICHLOROPHENE
    DICHLORVOS
    DICLAZURIL
    DICLOFENAC SODIUM
    DICLOXACILLIN SODIUM
    DICUMAROL
    DICYCLOMINE HYDROCHLORIDE
    DIENESTROL
    DIETHYLCARBAMAZINE CITRATE
    DIETHYLSTILBESTROL
    DIFLOXACIN HYDROCHLORIDE
    DIFLUNISAL
    DIGITOXIN
    DIGOXIN
    DIHYDROERGOTAMINE MESYLATE
    DIHYDROSTREPTOMYCIN SULFATE
    DILAZEP DIHYDROCHLORIDE
    DIMENHYDRINATE
    DIMERCAPROL
    DIMETHADIONE
    DIOXYBENZONE
    DIPHENHYDRAMINE HYDROCHLORIDE
    DIPHENYLPYRALINE HYDROCHLORIDE
    DIPYRIDAMOLE
    DIPYRONE
    DIRITHROMYCIN
    DISOPYRAMIDE PHOSPHATE
    DISULFIRAM
    DOBUTAMINE HYDROCHLORIDE
    DOCETAXEL
    DONEPEZIL HYDROCHLORIDE
    DOPAMINE HYDROCHLORIDE
    DOXEPIN HYDROCHLORIDE
    DOXOFYLLINE
    DOXYCYCLINE HYDROCHLORIDE
    DOXYLAMINE SUCCINATE
    DROFENINE HYDROCHLORIDE
    DROPERIDOL
    DROSPIRENONE
    DYCLONINE HYDROCHLORIDE
    DYPHYLLINE
    ECAMSULE TRIETHANOLAMINE
    ECONAZOLE NITRATE
    EDETATE DISODIUM
    EDITOL
    EDOXUDINE
    EMETINE
    ENALAPRIL MALEATE
    ENALAPRILAT
    ENOXACIN
    ENROFLOXACIN
    ENTACAPONE
    EPHEDRINE (1R,2S) HYDROCHLORIDE
    EPINEPHRINE BITARTRATE
    EPRINOMECTIN
    ERGOCALCIFEROL
    ERGONOVINE MALEATE
    ERYTHROMYCIN
    ERYTHROMYCIN ESTOLATE
    ERYTHROMYCIN ETHYLSUCCINATE
    ESCITALOPRAM OXALATE
    ESOMEPRAZOLE POTASSIUM
    ESTRADIOL
    ESTRADIOL BENZOATE
    ESTRADIOL CYPIONATE
    ESTRADIOL DIPROPIONATE
    ESTRADIOL VALERATE
    ESTRAMUSTINE
    ESTRIOL
    ESTRONE
    ESTROPIPATE
    ETHACRYNIC ACID
    ETHAMBUTOL HYDROCHLORIDE
    ETHAVERINE HYDROCHLORIDE
    ETHINYL ESTRADIOL
    ETHIONAMIDE
    ETHISTERONE
    ETHOPROPAZINE HYDROCHLORIDE
    ETHYL PARABEN
    ETODOLAC
    ETOPOSIDE
    EUCALYPTOL
    EUCATROPINE HYDROCHLORIDE
    EUGENOL
    EVANS BLUE
    EXEMESTANE
    EZETIMIBE
    FAMCICLOVIR
    FAMOTIDINE
    FAMPRIDINE
    FASUDIL HYDROCHLORIDE
    FEBUXOSTAT
    FENBENDAZOLE
    FENBUFEN
    FENDILINE HYDROCHLORIDE
    FENOFIBRATE
    FENOPROFEN
    FENOTEROL HYDROBROMIDE
    FENSPIRIDE HYDROCHLORIDE
    FEXOFENADINE HYDROCHLORIDE
    FIPEXIDE HYDROCHLORIDE
    FIROCOXIB
    FLOXURIDINE
    FLUCONAZOLE
    FLUDROCORTISONE ACETATE
    FLUFENAMIC ACID
    FLUINDAROL
    FLUMEQUINE
    FLUMETHASONE
    FLUMETHAZONE PIVALATE
    FLUNARIZINE HYDROCHLORIDE
    FLUNISOLIDE
    FLUNIXIN MEGLUMINE
    FLUOCINOLONE ACETONIDE
    FLUOCINONIDE
    FLUOROMETHOLONE
    FLUOROURACIL
    FLUOXETINE
    FLUPHENAZINE HYDROCHLORIDE
    FLURANDRENOLIDE
    FLURBIPROFEN
    FLUROFAMIDE
    FLUTAMIDE
    FLUVASTATIN
    FOLIC ACID
    FOSCARNET SODIUM
    FOSFOMYCIN CALCIUM
    FTAXILIDE
    FULVESTRANT
    FURAZOLIDONE
    FUROSEMIDE
    FUSIDIC ACID
    GABOXADOL HYDROCHLORIDE
    GADOTERIDOL
    GALANTHAMINE
    GALLAMINE TRIETHIODIDE
    GANCICLOVIR
    GATIFLOXACIN
    GEFITINIB
    GEMFIBROZIL
    GENTAMICIN SULFATE
    GENTIAN VIOLET
    GLIMEPIRIDE
    GLUCONOLACTONE
    GLUCOSAMINE HYDROCHLORIDE
    GLUTAMINE (D)
    GRAMICIDIN
    GRANISETRON HYDROCHLORIDE
    GRISEOFULVIN
    GUAIFENESIN
    GUANABENZ ACETATE
    GUANETHIDINE SULFATE
    HALAZONE
    HALCINONIDE
    HALOPERIDOL
    HEPTAMINOL HYDROCHLORIDE
    HETACILLIN POTASSIUM
    HEXACHLOROPHENE
    HEXYLRESORCINOL
    HISTAMINE DIHYDROCHLORIDE
    HOMATROPINE BROMIDE
    HOMATROPINE METHYLBROMIDE
    HOMOSALATE
    HYCANTHONE
    HYDRALAZINE HYDROCHLORIDE
    HYDRASTINE (1R, 9S)
    HYDROCHLOROTHIAZIDE
    HYDROCORTISONE
    HYDROCORTISONE ACETATE
    HYDROCORTISONE BUTYRATE
    HYDROCORTISONE HEMISUCCINATE
    HYDROCORTISONE PHOSPHATE TRIETHYLAMINE
    HYDROFLUMETHIAZIDE
    HYDROQUINONE
    HYDROXYAMPHETAMINE HYDROBROMIDE
    HYDROXYCHLOROQUINE SULFATE
    HYDROXYPROGESTERONE CAPROATE
    HYDROXYTOLUIC ACID
    HYDROXYUREA
    HYDROXYZINE PAMOATE
    HYOSCYAMINE
    IBANDRONATE SODIUM
    IBUPROFEN
    IDOXURDINE
    IDOXURIDINE
    IMIPRAMINE HYDROCHLORIDE
    IMIQUIMOD
    INAMRINONE
    INDAPAMIDE
    INDOMETHACIN
    INDOPROFEN
    INOSITOL
    IODIPAMIDE
    IODIXANOL
    IODOQUINOL
    IOHEXOL
    IOPANIC ACID
    IOTHALAMIC ACID
    IOVERSOL
    IOXILAN
    IPRATROPIUM BROMIDE
    IRBESARTAN
    ISONIAZID
    ISOPROPAMIDE IODIDE
    ISOPROTERENOL HYDROCHLORIDE
    ISOSORBIDE DINITRATE
    ISOSORBIDE MONONITRATE
    ISOTRETINON
    ISOXICAM
    ISOXSUPRINE HYDROCHLORIDE
    ITOPRIDE HYDROCHLORIDE
    IVERMECTIN
    KANAMYCIN A SULFATE
    KETOCONAZOLE
    KETOPROFEN
    KETOROLAC TROMETHAMINE
    KETOTIFEN FUMARATE
    LABETALOL HYDROCHLORIDE
    LACTULOSE
    LAMIVUDINE
    LANATOSIDE C
    LANSOPRAZOLE
    LEFLUNOMIDE
    LETROZOLE
    LEUCOVORIN CALCIUM
    LEVAMISOLE HYDROCHLORIDE
    LEVOCETIRIZINE DIHYDROCHLORIDE
    LEVOFLOXACIN
    LEVOMENTHOL
    LEVONORDEFRIN
    LEVONORGESTREL
    LEVOSIMENDAN
    LEVOTHYROXINE
    LIDOCAINE HYDROCHLORIDE
    LINCOMYCIN HYDROCHLORIDE
    LINDANE
    LINEZOLID
    LIOTHYRONINE
    LIOTHYRONINE (L- isomer) SODIUM
    LISINOPRIL
    LITHIUM CITRATE
    LOBELINE HYDROCHLORIDE
    LOFEXIDINE HYDROCHLORIDE
    LOMEFLOXACIN HYDROCHLORIDE
    LOMERIZINE HYDROCHLORIDE
    LOMUSTINE
    LORATADINE
    LORNOXICAM
    LOSARTAN
    LOVASTATIN
    LUMIRACOXIB
    MAFENIDE HYDROCHLORIDE
    MALATHION
    MANGAFODIPIR TRISODIUM
    MANIDIPINE HYDROCHLORIDE
    MANNITOL
    MAPROTILINE HYDROCHLORIDE
    MEBENDAZOLE
    MEBEVERINE HYDROCHLORIDE
    MEBHYDROLIN NAPHTHALENESULFONATE
    MECAMYLAMINE HYDROCHLORIDE
    MECHLORETHAMINE
    MECLIZINE HYDROCHLORIDE
    MECLOCYCLINE SULFOSALICYLATE
    MECLOFENAMATE SODIUM
    MECLOFENOXATE HYDROCHLORIDE
    MEDROXYPROGESTERONE ACETATE
    MEDRYSONE
    MEFENAMIC ACID
    MEFEXAMIDE
    MEFLOQUINE
    MEGESTROL ACETATE
    MEGLUMINE
    MELOXICAM SODIUM
    MELPERONE HYDROCHLORIDE
    MELPHALAN
    MEMANTINE HYDROCHLORIDE
    MENADIONE
    MEPARTRICIN
    MEPENZOLATE BROMIDE
    MEPHENESIN
    MEPHENTERMINE SULFATE
    MEPIVACAINE HYDROCHLORIDE
    MEQUINOL
    MERBROMIN
    MERCAPTOPURINE
    MEROPENEM
    MESNA
    MESO-ERYTHRITOL
    MESTRANOL
    METAPROTERENOL
    METARAMINOL BITARTRATE
    METAXALONE
    METHACHOLINE CHLORIDE
    METHACYCLINE HYDROCHLORIDE
    METHAPYRILENE HYDROCHLORIDE
    METHAZOLAMIDE
    METHENAMINE
    METHICILLIN SODIUM
    METHIMAZOLE
    METHOCARBAMOL
    METHOTREXATE(+/-)
    METHOXAMINE HYDROCHLORIDE
    METHOXSALEN
    METHSCOPOLAMINE BROMIDE
    METHYCLOTHIAZIDE
    METHYLBENZETHONIUM CHLORIDE
    METHYLDOPA
    METHYLERGONOVINE MALEATE
    METHYLPREDNISOLONE
    METHYLPREDNISOLONE SODIUM SUCCINATE
    METHYLTHIOURACIL
    METOCLOPRAMIDE HYDROCHLORIDE
    METOPROLOL TARTRATE
    METRONIDAZOLE
    MEXILETINE HYDROCHLORIDE
    MICONAZOLE NITRATE
    MIDODRINE HYDROCHLORIDE
    MIGLITOL
    MILNACIPRAN HYDROCHLORIDE
    MINAPRINE HYDROCHLORIDE
    MINOCYCLINE HYDROCHLORIDE
    MINOXIDIL
    MITOMYCIN C
    MITOTANE
    MITOXANTRONE HYDROCHLORIDE
    MOLSIDOMINE
    MONENSIN SODIUM (monensin A is shown)
    MONOBENZONE
    MORANTEL CITRATE
    MOXALACTAM DISODIUM
    MOXIFLOXACIN HYDROCHLORIDE
    MYCOPHENOLATE MOFETIL
    MYCOPHENOLIC ACID
    NABUMETONE
    NADIDE
    NADOLOL
    NAFCILLIN SODIUM
    NAFRONYL OXALATE
    NALBUPHINE HYDROCHLORIDE
    NALIDIXIC ACID
    NALOXONE HYDROCHLORIDE
    NALTREXONE HYDROCHLORIDE
    NAPHAZOLINE HYDROCHLORIDE
    NAPROXEN(+)
    NAPROXOL
    NATEGLINIDE
    NEFAZODONE HYDROCHLORIDE
    NEFOPAM
    NELARABIN
    NEOMYCIN SULFATE
    NEOSTIGMINE BROMIDE
    NEVIRAPINE
    NIACIN
    NICARDIPINE HYDROCHLORIDE
    NICERGOLINE
    NICLOSAMIDE
    NICOTINYL ALCOHOL TARTRATE
    NIFEDIPINE
    NIFURSOL
    NILUTAMIDE
    NIMODIPINE
    NITAZOXANIDE
    NITRENDIPINE
    NITROFURANTOIN
    NITROFURAZONE
    NITROMIDE
    NOCODAZOLE
    NOMIFENSINE MALEATE
    NOREPINEPHRINE
    NORETHINDRONE
    NORETHINDRONE ACETATE
    NORETHYNODREL
    NORFLOXACIN
    NORGESTREL
    NORTRIPTYLINE
    NOSCAPINE HYDROCHLORIDE
    NOVOBIOCIN SODIUM
    NYLIDRIN HYDROCHLORIDE
    NYSTATIN
    OCTOPAMINE HYDROCHLORIDE
    OFLOXACIN
    OLMESARTAN
    OLMESARTAN MEDOXOMIL
    OLSALAZINE SODIUM
    OLSELTAMIVIR PHOSPHATE
    OMEGA-3-ACID ESTERS (EPA shown)
    ONDANSETRON
    ORLISTAT
    ORPHENADRINE CITRATE
    OUABAIN
    OXACILLIN SODIUM
    OXALIPLATIN
    OXCARBAZEPINE
    OXETHAZAINE
    OXIBENDAZOLE
    OXIDOPAMINE HYDROCHLORIDE
    OXOLINIC ACID
    OXYBENZONE
    OXYMETAZOLINE HYDROCHLORIDE
    OXYPHENBUTAZONE
    OXYPHENCYCLIMINE HYDROCHLORIDE
    OXYQUINOLINE HEMISULFATE
    OXYTETRACYCLINE
    PACLITAXEL
    PALIPERIDONE
    PAPAVERINE HYDROCHLORIDE
    PARACHLOROPHENOL
    PARAROSANILINE PAMOATE
    PARGYLINE HYDROCHLORIDE
    PAROMOMYCIN SULFATE
    PAROXETINE HYDROCHLORIDE
    PEMETREXED
    PENCICLOVIR
    PENICILLAMINE
    PENICILLIN G POTASSIUM
    PENICILLIN V POTASSIUM
    PENTOLINIUM TARTRATE
    PENTOXIFYLLINE
    PERGOLIDE MESYLATE
    PERHEXILINE MALEATE
    PERICIAZINE
    PERINDOPRIL ERBUMINE
    PERPHENAZINE
    PHENACEMIDE
    PHENAZOPYRIDINE HYDROCHLORIDE
    PHENELZINE SULFATE
    PHENINDIONE
    PHENIRAMINE MALEATE
    PHENOLPHTHALEIN
    PHENTOLAMINE HYDROCHLORIDE
    PHENYL AMINOSALICYLATE
    PHENYLBUTAZONE
    PHENYLEPHRINE HYDROCHLORIDE
    PHENYLMERCURIC ACETATE
    PHENYLPROPANOLAMINE HYDROCHLORIDE
    PHENYTOIN SODIUM
    PHTHALYLSULFATHIAZOLE
    PHYSOSTIGMINE SALICYLATE
    PILOCARPINE NITRATE
    PIMOZIDE
    PINDOLOL
    PIOGLITAZONE HYDROCHLORIDE
    PIPERACETAZINE
    PIPERACILLIN SODIUM
    PIPERAZINE
    PIPERIDOLATE HYDROCHLORIDE
    PIPERINE
    PIPOBROMAN
    PIRACETAM
    PIRENPERONE
    PIRENZEPINE HYDROCHLORIDE
    PIROCTONE OLAMINE
    PIROXICAM
    PITAVASTATIN CALCIUM
    PIZOTYLINE MALATE
    POLYMYXIN B SULFATE
    POTASSIUM p-AMINOBENZOATE
    PRAMIPEXOLE DIHYDROCHLORIDE
    PRAMOXINE HYDROCHLORIDE
    PRASUGREL
    PRAZIQUANTEL
    PRAZOSIN HYDROCHLORIDE
    PREDNICARBATE
    PREDNISOLONE
    PREDNISOLONE ACETATE
    PREDNISONE
    PRILOCAINE HYDROCHLORIDE
    PRIMAQUINE DIPHOSPHATE
    PRIMIDONE
    PROADIFEN HYDROCHLORIDE
    PROBENECID
    PROBUCOL
    PROCAINAMIDE HYDROCHLORIDE
    PROCAINE HYDROCHLORIDE
    PROCARBAZINE HYDROCHLORIDE
    PROCHLORPERAZINE EDISYLATE
    PROCYCLIDINE HYDROCHLORIDE
    PROGESTERONE
    PROGLUMIDE
    PROMAZINE HYDROCHLORIDE
    PROMETHAZINE HYDROCHLORIDE
    PRONETALOL HYDROCHLORIDE
    PROPAFENONE HYDROCHLORIDE
    PROPANTHELINE BROMIDE
    PROPIOLACTONE
    PROPOFOL
    PROPYLTHIOURACIL
    PSEUDOEPHEDRINE HYDROCHLORIDE
    PUROMYCIN HYDROCHLORIDE
    PYRANTEL PAMOATE
    PYRAZINAMIDE
    PYRETHRINS
    PYRIDOSTIGMINE BROMIDE
    PYRILAMINE MALEATE
    PYRIMETHAMINE
    PYRITHIONE ZINC
    PYRONARIDINE TETRAPHOSPHATE
    PYRVINIUM PAMOATE
    QUETIAPINE
    QUINACRINE HYDROCHLORIDE
    QUINAPRIL HYDROCHLORIDE
    QUINESTROL
    QUINETHAZONE
    QUINIDINE GLUCONATE
    QUININE SULFATE
    QUIPAZINE MALEATE
    RACEPHEDRINE HYDROCHLORIDE
    RACTOPAMINE HYDROCHLORIDE
    RAMIPRIL
    RAMOPLANIN [A2 shown; 2mm]
    RANITIDINE
    RASAGILINE
    RESERPINE
    RESORCINOL
    RESORCINOL MONOACETATE
    RETAPAMULIN
    RETINOL
    RETINYL PALMITATE
    RIBAVIRIN
    RIFAMPIN
    RITANSERIN
    RITODRINE HYDROCHLORIDE
    RITONAVIR
    RIZATRIPTAN BENZOATE
    ROFECOXIB
    RONIDAZOLE
    ROPINIROLE
    ROSIGLITAZONE
    ROSUVASTATIN CALCIUM
    ROXARSONE
    ROXATIDINE ACETATE HYDROCHLORIDE
    ROXITHROMYCIN
    RUFLOXACIN HYDROCHLORIDE
    SACCHARIN
    SALICIN
    SALICYL ALCOHOL
    SALICYLAMIDE
    SALICYLANILIDE
    SALINOMYCIN, SODIUM
    SALSALATE
    SANGUINARINE SULFATE
    SCOPOLAMINE HYDROBROMIDE
    SELAMECTIN
    SEMUSTINE
    SENNOSIDE A
    SERATRODAST
    SERTRALINE HYDROCHLORIDE
    SEVOFLURANE
    SIBUTRAMINE HYDROCHLORIDE
    SILDENAFIL CITRATE
    SIMVASTATIN
    SIROLIMUS
    SISOMICIN SULFATE
    SODIUM DEHYDROCHOLATE
    SODIUM NITROPRUSSIDE
    SODIUM OXYBATE
    SODIUM PHENYLACETATE
    SODIUM PHENYLBUTYRATE
    SODIUM SALICYLATE
    SPARFLOXACIN
    SPARTEINE SULFATE
    SPECTINOMYCIN HYDROCHLORIDE
    SPIPERONE
    SPIRAMYCIN
    SPIRAPRIL HYDROCHLORIDE
    SPIRONOLACTONE
    STAVUDINE
    STREPTOMYCIN SULFATE
    STREPTOZOSIN
    SUCCINYLSULFATHIAZOLE
    SULBACTAM
    SULCONAZOLE NITRATE
    SULFABENZAMIDE
    SULFACETAMIDE
    SULFACHLORPYRIDAZINE
    SULFADIAZINE
    SULFADIMETHOXINE
    SULFAMERAZINE
    SULFAMETER
    SULFAMETHAZINE
    SULFAMETHIZOLE
    SULFAMETHOXAZOLE
    SULFAMETHOXYPYRIDAZINE
    SULFAMONOMETHOXINE
    SULFANILATE ZINC
    SULFANITRAN
    SULFAPYRIDINE
    SULFAQUINOXALINE SODIUM
    SULFASALAZINE
    SULFATHIAZOLE
    SULFINPYRAZONE
    SULFISOXAZOLE
    SULINDAC
    SULMAZOLE
    SULOCTIDIL
    SULPIRIDE
    SUPROFEN
    SURAMIN
    TACROLIMUS
    TAMOXIFEN CITRATE
    TANDUTINIB
    TANNIC ACID
    TAZOBACTAM
    TEGASEROD MALEATE
    TELMISARTAN
    TEMEFOS
    TEMOZOLAMIDE
    TENIPOSIDE
    TENOXICAM
    TERBUTALINE HEMISULFATE
    TERCONAZOLE
    TERFENADINE
    TESTOSTERONE
    TESTOSTERONE PROPIONATE
    TETRACAINE HYDROCHLORIDE
    TETRACYCLINE HYDROCHLORIDE
    TETRAHYDROZOLINE HYDROCHLORIDE
    TETROQUINONE
    THALIDOMIDE
    THEOBROMINE
    THEOPHYLLINE
    THIABENDAZOLE
    THIAMPHENICOL
    THIMEROSAL
    THIOGUANINE
    THIORIDAZINE HYDROCHLORIDE
    THIOSTREPTON
    THIOTEPA
    THIOTHIXENE
    THIRAM
    THONZONIUM BROMIDE
    THONZYLAMINE HYDROCHLORIDE
    TIAPRIDE HYDROCHLORIDE
    TIBOLONE
    TIGECYCLINE
    TILARGININE HYDROCHLORIDE
    TILETAMINE HYDROCHLORIDE
    TILMICOSIN
    TIMOLOL MALEATE
    TINIDAZOLE
    TOBRAMYCIN
    TODRALAZINE HYDROCHLORIDE
    TOLAZAMIDE
    TOLAZOLINE HYDROCHLORIDE
    TOLBUTAMIDE
    TOLMETIN SODIUM
    TOLNAFTATE
    TOLPERISONE HYDROCHLORIDE
    TOSYLCHLORAMIDE SODIUM
    TRANEXAMIC ACID
    TRANYLCYPROMINE SULFATE
    TRAZODONE HYDROCHLORIDE
    TRETINOIN
    TRIACETIN
    TRIAMCINOLONE
    TRIAMCINOLONE ACETONIDE
    TRIAMCINOLONE DIACETATE
    TRIAMTERENE
    TRICHLORMETHIAZIDE
    TRIFLUOPERAZINE HYDROCHLORIDE
    TRIFLUPROMAZINE HYDROCHLORIDE
    TRIFLURIDINE
    TRIHEXYPHENIDYL HYDROCHLORIDE
    TRILOSTANE
    TRIMEPRAZINE TARTRATE
    TRIMETHOBENZAMIDE HYDROCHLORIDE
    TRIMETHOPRIM
    TRIMETOZINE
    TRIMIPRAMINE MALEATE
    TRIOXSALEN
    TRIPELENNAMINE CITRATE
    TRIPROLIDINE HYDROCHLORIDE
    TRISODIUM ETHYLENEDIAMINE TETRACETATE
    TROLEANDOMYCIN
    TROPICAMIDE
    TROPISETRON HYDROCHLORIDE
    TRYPTOPHAN
    TUAMINOHEPTANE SULFATE
    TUBOCURARINE CHLORIDE
    TYROTHRICIN
    URACIL
    URAPIDIL HYDROCHLORIDE
    UREA
    URETHANE
    URSODIOL
    VALDECOXIB
    VALGANCICLOVIR HYDROCHLORIDE
    VALPROATE SODIUM
    VALSARTAN
    VANCOMYCIN HYDROCHLORIDE
    VENLAFAXINE
    VIDARABINE
    VINBLASTINE SULFATE
    VINORELBINE
    VINPOCETINE
    VIOMYCIN SULFATE
    VORICONAZOLE
    VORINOSTAT
    WARFARIN
    XYLAZINE
    XYLOMETAZOLINE HYDROCHLORIDE
    YOHIMBINE HYDROCHLORIDE
    ZALCITABINE
    ZAPRINAST
    ZIDOVUDINE [AZT]
    ZIPRASIDONE MESYLATE
    ZOMEPIRAC SODIUM
    ZOPICLONE
    • View popup
    Table 2:

    List of compounds exhibiting toxicity.

    ABACAVIR SULFATE
    ACIPIMOX
    ADENOSINE PHOSPHATE
    ALAPROCLATE
    AMLEXANOX
    AMOROLFINE HYDROCHLORIDE
    ANTAZOLINE PHOSPHATE
    ARTEMETHER
    ASCORBIC ACID
    ATORVASTATIN CALCIUM
    AUROTHIOGLUCOSE
    AZELAIC ACID
    BENORILATE
    BENZONATATE
    BETAINE HYDROCHLORIDE
    BETAMIPRON
    BROMHEXINE HYDROCHLORIDE
    BUDESONIDE
    BUPIVACAINE HYDROCHLORIDE
    BUSULFAN
    BUTOCONAZOLE
    CAPSAICIN
    CARPROFEN
    CEFORANIDE
    CEFOTAXIME SODIUM
    CEFOXITIN SODIUM
    CEPHALEXIN
    CHLORAMBUCIL
    CHLORAMPHENICOL HEMISUCCINATE
    CHLOROGUANIDE HYDROCHLORIDE
    CHLORPHENIRAMINE (S) MALEATE
    CINCHOPHEN
    CINNARAZINE
    CINTRIAMIDE
    CIPROFLOXACIN
    CLIDINIUM BROMIDE
    CLOZAPINE
    COLISTIMETHATE SODIUM
    CRYOFLURANE
    CYCLOPHOSPHAMIDE HYDRATE
    CYCLOTHIAZIDE
    CYPERMETHRIN
    DAUNORUBICIN
    DECIMEMIDE
    DEXTROMETHORPHAN HYDROBROMIDE
    DICHLOROPHENE
    DIETHYLCARBAMAZINE CITRATE
    DIOXYBENZONE
    DIRITHROMYCIN
    DISOPYRAMIDE PHOSPHATE
    DISULFIRAM
    ECONAZOLE NITRATE
    EDETATE DISODIUM
    EMETINE
    ENALAPRILAT
    ERYTHROMYCIN
    ETHINYL ESTRADIOL
    ETHIONAMIDE
    ETHOPROPAZINE HYDROCHLORIDE
    ETHYL PARABEN
    EUGENOL
    FIPEXIDE HYDROCHLORIDE
    FLUMETHASONE
    FLUNISOLIDE
    FLUVASTATIN
    GEMFIBROZIL
    GENTAMICIN SULFATE
    GLUCONOLACTONE
    HALAZONE
    HALCINONIDE
    HETACILLIN POTASSIUM
    HEXACHLOROPHENE
    HOMATROPINE METHYLBROMIDE
    HYDRASTINE (1R, 9S)
    HYDROXYAMPHETAMINE HYDROBROMIDE
    HYDROXYCHLOROQUINE SULFATE
    IODIXANOL
    IOHEXOL
    IRBESARTAN
    LEVOSIMENDAN
    LISINOPRIL
    LOMERIZINE HYDROCHLORIDE
    MANGAFODIPIR TRISODIUM
    MECLOFENOXATE HYDROCHLORIDE
    MESTRANOL
    METHACHOLINE CHLORIDE
    METHYLERGONOVINE MALEATE
    METRONIDAZOLE
    MIGLITOL
    MONENSIN SODIUM (monensin A is shown)
    MONOBENZONE
    MOXALACTAM DISODIUM
    NADOLOL
    NALBUPHINE HYDROCHLORIDE
    NALTREXONE HYDROCHLORIDE
    NAPHAZOLINE HYDROCHLORIDE
    NAPROXEN(+)
    NEOMYCIN SULFATE
    NIFEDIPINE
    NITAZOXANIDE
    NITROMIDE
    NORETHINDRONE
    OLMESARTAN MEDOXOMIL
    OXYMETAZOLINE HYDROCHLORIDE
    PARACHLOROPHENOL
    PAROMOMYCIN SULFATE
    PERHEXILINE MALEATE
    PHENTOLAMINE HYDROCHLORIDE
    PHENYLBUTAZONE
    PHENYLMERCURIC ACETATE
    PHYSOSTIGMINE SALICYLATE
    PIMOZIDE
    PIPERACILLIN SODIUM
    PIPERAZINE
    PIRACETAM
    PIRENZEPINE HYDROCHLORIDE
    PIROCTONE OLAMINE
    PITAVASTATIN CALCIUM
    PRIMAQUINE DIPHOSPHATE
    PROBENECID
    PROCARBAZINE HYDROCHLORIDE
    PROGLUMIDE
    PROMETHAZINE HYDROCHLORIDE
    PUROMYCIN HYDROCHLORIDE
    QUININE SULFATE
    RETINYL PALMITATE
    RIFAMPIN
    RITONAVIR
    ROFECOXIB
    RUFLOXACIN HYDROCHLORIDE
    SACCHARIN
    SALICIN
    SENNOSIDE A
    STAVUDINE
    STREPTOMYCIN SULFATE
    SULFADIAZINE
    SULINDAC
    SULOCTIDIL
    TANNIC ACID
    TELMISARTAN
    TENOXICAM
    THEOPHYLLINE
    TILETAMINE HYDROCHLORIDE
    TILMICOSIN
    TIMOLOL MALEATE
    TOLBUTAMIDE
    TOLNAFTATE
    TRAZODONE HYDROCHLORIDE
    TRETINOIN
    TRIFLUPROMAZINE HYDROCHLORIDE
    TROPISETRON HYDROCHLORIDE
    VALDECOXIB
    VORINOSTAT
    ZALCITABINE
    • View popup
    Table 3:

    List of compounds exhibiting hyperexcitable or proconvulsant activity.

    ADENOSINE PHOSPHATE
    ALBUTEROL (+/-)
    ALEXIDINE HYDROCHLORIDE
    AMANTADINE HYDROCHLORIDE
    AMINOHIPPURIC ACID
    AMINOLEVULINIC ACID HYDROCHLORIDE
    AUROTHIOGLUCOSE
    AZACITIDINE
    BENZOYL PEROXIDE
    BETAZOLE HYDROCHLORIDE
    BROMHEXINE HYDROCHLORIDE
    BUSULFAN
    CEFSULODIN SODIUM
    CEFUROXIME AXETIL
    CHLOROGUANIDE HYDROCHLORIDE
    CYSTEAMINE HYDROCHLORIDE
    ECAMSULE TRIETHANOLAMINE
    ECONAZOLE NITRATE
    EDOXUDINE
    ENROFLOXACIN
    ESTRADIOL CYPIONATE
    ETHINYL ESTRADIOL
    ETHOPROPAZINE HYDROCHLORIDE
    ETOPOSIDE
    FASUDIL HYDROCHLORIDE
    FEBUXOSTAT
    FLUMETHASONE
    FLUOROMETHOLONE
    FURAZOLIDONE
    GANCICLOVIR
    GLUCONOLACTONE
    GRANISETRON HYDROCHLORIDE
    HALAZONE
    HEXACHLOROPHENE
    IODIPAMIDE
    LABETALOL HYDROCHLORIDE
    MEPIVACAINE HYDROCHLORIDE
    MITOXANTRONE HYDROCHLORIDE
    MORANTEL CITRATE
    NOCODAZOLE
    OFLOXACIN
    PENTOLINIUM TARTRATE
    PERINDOPRIL ERBUMINE
    PIOGLITAZONE HYDROCHLORIDE
    PRAMIPEXOLE DIHYDROCHLORIDE
    PROGLUMIDE
    RIFAMPIN
    SERATRODAST
    SERTRALINE HYDROCHLORIDE
    SIBUTRAMINE HYDROCHLORIDE
    SUCCINYLSULFATHIAZOLE
    TACROLIMUS
    TETROQUINONE
    TIMOLOL MALEATE
    URACIL
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eneuro: 2 (4)
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July/August 2015
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Large-Scale Phenotype-Based Antiepileptic Drug Screening in a Zebrafish Model of Dravet Syndrome
Matthew T. Dinday, Scott C. Baraban
eNeuro 20 August 2015, 2 (4) ENEURO.0068-15.2015; DOI: 10.1523/ENEURO.0068-15.2015

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Large-Scale Phenotype-Based Antiepileptic Drug Screening in a Zebrafish Model of Dravet Syndrome
Matthew T. Dinday, Scott C. Baraban
eNeuro 20 August 2015, 2 (4) ENEURO.0068-15.2015; DOI: 10.1523/ENEURO.0068-15.2015
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  • antiepileptic
  • drug discovery
  • epilepsy
  • high throughput
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