Dose-dependent subacute cardiovascular effects of modafinil in rats.

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.

• Authors: Dilan Canyurt, Lokman Hekim Tanriverdi, Onural Ozhan, Mehmet Cansel, Hakan Parlakpinar, Nigar Vardi, Yilmaz Cigremis, Azibe Yildiz, Yucel Karaca, Seyma Yasar, Ahmet Acet
• Journal: Drug and chemical toxicology (Drug Chem Toxicol) Vol. 45 Issue 3 Pg. 1044-1053 (May 2022) ISSN: 1525-6014 [Electronic] United States
• PMID: 32777970 (Publication Type: Journal Article)

Chemical References

• Malondialdehyde
• Modafinil

Topics

• Animals
• Heart
• Malondialdehyde (metabolism)
• Modafinil (toxicity)
• Myocardium (metabolism)
• Oxidative Stress
• Rats
• Rats, Wistar