Lethal ventricular arrhythmias have occurred in patients taking thioridazine. Therefore, we studied two canine models to determine if thioridazine alters vulnerability to ventricular fibrillation. In 30 chloralose-anesthetized dogs, the repetitive response threshold was used to assess vulnerability during right ventricular stimulation with transvenous catheter electrodes. Placebo, 10 mg/kg of thioridazine (therapeutic dose) or 30 mg/kg of thioridazine (high dose) was infused i.v. (n = 10 each group). Repetitive response threshold, diastolic excitability, QRS, Q-Tc and plasma thioridazine concentrations were measured before and after drug. Both 10 and 30 mg/kg of thioridazine increased diastolic excitability threshold (P < .05) while only the 30 mg/kg dose widened QRS (P < .05) and prolonged Q-Tc (P < .05). RRT was unchanged. In 45 pentobarbital-anesthetized dogs, one stage ligation of the left anterior descending coronary artery was performed after pretreatment with placebo, 10 or 30 mg/kg of thioridazine (n = 15 each group). Spontaneous ventricular fibrillation occurred in 6 of 15 dogs (40%) after placebo, 8 of 15 dogs (53%) after 10 mg/kg of thioridazine and 14 of 15 dogs (93%) after 30 mg/ kg of thioridazine. Although thioridazine depressed excitability and had no effect on electrical fibrillation threshold, the 30 mg/kg dose increased the likelihood of spontaneous ventricular fibrillation during acute ischemia.
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Acta Parasitol
March 2024
Centro de Bioactivos Químicos, Universidad Central "Martha Abreu" de Las Villas, Santa Clara, Villa Clara, Cuba.
Introduction: Leishmaniasis is a neglected disease with high prevalence and incidence in tropical and subtropical areas. Existing drugs are limited due to cost, toxicity, declining efficacy and unavailability in endemic places. Drug repurposing has established as an efficient way for the discovery of drugs for a variety of diseases.
View Article and Find Full Text PDFJ Pharmacol Toxicol Methods
May 2022
13765 Seabiscuit Drive, Reno, NV 89521, USA. Electronic address:
Pending updates to ICH S7B/E14 guidelines will enable the substitution of human TQT studies with support from concomitant negative hERG and non-rodent CV studies. This retrospective analysis compared the effects of thioridazine (THD) (5-20 mg/kg) on heart rate (HR), blood pressure (BP), body temperature (Tc), and QT in the dog (n = 6), cynomolgus monkey (n = 4), and Goettingen minipig (n = 4) with data from previously completed studies employing crossover designs. As QT measurements are confounded by HR and Tc changes, QT effects were individually corrected for changes in HR (QTca) and Tc (QTcaT).
View Article and Find Full Text PDFPLoS One
November 2021
Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
The rapid evolution of antibiotic resistance in Clostridioides difficile and the consequent effects on prevention and treatment of C. difficile infections (CDIs) are matters of concern for public health. Thioridazine, a compound belonging to the phenothiazine group, has previous shown antimicrobial activity against C.
View Article and Find Full Text PDFInt Immunopharmacol
August 2020
Institute of Biomedical Sciences, Federal University of Alfenas, Alfenas 37130-001, Minas Gerais, Brazil; Department of Structural Biology, Federal University of Alfenas, Alfenas 37130-001, Minas Gerais, Brazil. Electronic address:
While thioridazine (Tio) inhibits the antioxidant defenses of Trypanosoma cruzi, the gold standard antitrypanosomal drug benznidazole (Bz) has potent anti-inflammatory and pro-oxidant properties. The combination of these drugs has never been tested to determine the effect on T. cruzi infection.
View Article and Find Full Text PDFPharmacol Res
August 2020
Institute of Biomedical Sciences, Federal University of Alfenas, Alfenas, 37130-001 Minas Gerais, Brazil; Department of Structural Biology, Federal University of Alfenas, Alfenas, 37130-001 Minas Gerais, Brazil. Electronic address:
Phenothiazines inhibit major antioxidant defense mechanisms in trypanosomatids and exhibit potent cytotoxic effects in vitro. However, the relevance of these drugs in the treatment of Trypanosoma cruzi-induced acute myocarditis is poorly explored, especially in combination with reference trypanocidal drugs. Thus, we compared the antiparasitic and cardioprotective potential of thioridazine (TDZ) and benznidazole (Bz) administered in monotherapy and combined in a murine model of T.
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