Dose-dependent subacute cardiovascular effects of modafinil in rats

Drug Chem Toxicol. 2022 May;45(3):1044-1053. doi: 10.1080/01480545.2020.1803906. Epub 2020 Aug 11.

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.

Keywords: Atrioventricular blockage; cardiotoxicity; drug toxicity; experimental toxicology; modafinil.

MeSH terms

  • Animals
  • Heart*
  • Malondialdehyde / metabolism
  • Modafinil / toxicity
  • Myocardium* / metabolism
  • Oxidative Stress
  • Rats
  • Rats, Wistar

Substances

  • Malondialdehyde
  • Modafinil