Cardiotoxicity Studies in Zebrafish - Zebrafish: Methods for Assessing Drug Safety and Toxicity - page 55

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Acemetacion HCTZ

Ibutilide
Isoproterenol
Ketansrin
Ketoconazole
L-Dopa
Lithium chloride
Methotnexate
Metronidazole
Mevastatin
Minoxidil
NAPA
Neostigmine

Acetaminophenol

Acetazolamide

Acetylcholine

Accyolovir

Allopurinol

Amantadine

Aminophenylsulfone

Amiodarone

Amitryptiline

Amrinone

Arginine

Asfemizole

Atropine Nicotine

Azithromycin Nitro-arginine

Nitroprusside
Nocodazole
Norepinephrine
Ouabain
Penicillin
Pentamidine
Pentoxyfilline
Phenylephrine
Phenytoin
Pimozide
Piroxicam
Prazosin
Procainamide
Progesterone
Propranolol
Quinidine
Reserpine
Rifampin
Ritodrine
Ryanodine
Salbutamol
Scopolactoned
D.L- Sotalol
Spironolactone
Tamoxifen
Ta x o l
Tensilon
Terfenadin
Theophyline
Thioridazine
Tolbutamide
Valproic acid
Verapamil
Warfarin

Baclofen

Bromocryptine

Caffeine

Captopril

Carbamazepine

Carbidopa

Cetriaxone

Chlorpromazine

Ciglitazone

Cimetidine

Ciprofloxacin

Cisapride

Clonidine

Clozapine

Colchicine

Dantrolene

Demedocydine

Dexamethasone

Digitoxin

Dimethylbiguanide

Diphenhydramine

Dobutamine

Dopamine

Droperidol

E-4031

Epinephrine

Erythromycin

Estradiol

Etoposide

Flecainide

Fluoxetine

Furosemide

Genistein

Glybenolamide

Haloperidol Yohirrbine

Figure 5.1 Screening 100 compounds for heart rate effects in zebrafish. Heart rates are normalized to
vehicle controls. Mean heart rate and standard deviation are shown. Compounds listed in red prolong the QT
interval in humans and have been associated with TdP. Blue color indicates association with QT prolongation,
but not TdP in humans. Open diamonds signify a statistically significant difference from control (p < 0.05).
(Figure adapted from Milan et al., 2003.) (See the color version of this figure in Color Plates section.)

TdP in humans consistently resulted in bradycardia and/or atrioventricular block in
the zebrafish. Figure 5.1 shows the effects of 100 biologically active small
molecules on zebrafish heart rate. Thirty-six compounds caused bradycardia, of
which 18 were known in humans to result in QT prolongation and TdP. Five of
the 23 compounds (erythromycin, N-acetylprocainamide (NAPA), pentamidine,