Dose-dependent subacute cardiovascular effects of modafinil in rats. (4th May 2022)

• Record Type: Journal Article
• Authors: Canyurt, Dilan; Tanriverdi, Lokman Hekim; Ozhan, Onural; Cansel, Mehmet; Parlakpinar, Hakan; Vardi, Nigar; Cigremis, Yilmaz; Yildiz, Azibe; Karaca, Yucel; Yasar, Seyma; Acet, Ahmet
• Is Part Of: Drug and chemical toxicology. Volume 45:Number 3(2022)
• Page Start: 1044
• Page End: 1053
• Publication Date: 2022-05-04
• Subjects: Atrioventricular blockage -- cardiotoxicity -- drug toxicity -- experimental toxicology -- modafinil; Toxicology -- Periodicals; Drugs -- Toxicology -- Periodicals; Toxicology, Experimental -- Periodicals; 615.9005
• DOI: 10.1080/01480545.2020.1803906
• Languages: English
• ISSNs: 0148-0545

Abstract

Abstract: Modafinil is used for the treatment of various sleep disorders; however, its usage among healthy individuals is also increasing. There are a limited number of cardiovascular side effects, including ischemic T-wave changes, dyspnea, hypertension, and tachycardia in the literature. Our research aimed to investigate the dose-dependent subacute cardiovascular effects of modafinil in rats. Thirty-two rats were randomly and equally assigned to a control group (vehicle-treated for 14 days), a subacute low-dose group (SALD, 10 mg/kg for 14 days), a subacute moderate-dose group (SAMD, 100 mg/kg for 14 days), and a subacute high-dose group (SHD, 600 mg/kg for 14 days). The cardiovascular effects of modafinil were evaluated using hemodynamic, biochemical, electrocardiographic, electrophysiologic, and histopathologic parameters. In terms of hemodynamic parameters, heart rate, and systolic/diastolic/mean blood pressure levels, electrophysiological parameters did not reach statistical significance among the groups ( p > 0.05). The incidence of T-wave negativity in SAMD and SAHD groups was 25 and 37.5%, respectively. Moreover, one rat per group was affected by an atrioventricular blockage. Malondialdehyde, superoxide dismutase, catalase, and reduced glutathione levels in the heart and vascular tissues, serum troponin-I, and creatine kinase levels were similar between the modafinil-administered groups and the control group ( p > 0.05); this indicates that modafinil activated neither oxidative stress nor antioxidant pathway. Also, there was no difference in histopathological parameters between groups ( p > 0.05). Supratherapeutic doses of modafinil may have the potential to cause ischemic cardiac damage and atrioventricular blockage, despite inconsistency with literature findings; however, this does not pertain to hemodynamic changes.