The present study investigates the antiParkinsonian activity of dipeptidyl peptidase‑4 (DPP‑IV) inhibitor,
linagliptin. The experimental Parkinson’s disease (PD) was induced by administration of rotenone at a
dose of 1.5 mg/kg at alternate day subcutaneously for 21 days. Standard drug (levodopa‑200 mg/kg
and carbidopa‑50 mg/kg) and treatment drug (linagliptin‑5 mg/kg, 10 mg/kg, and 20mg/kg) were
administered orally daily 1 h before rotenone administration. In a rat rotenone model, linagliptin
improved muscle coordination, motor performance, and corrected akinesia. Pretreatment with
linagliptin showed significant higher levels of superoxide dismutase, catalase, and glutathione in
brain homogenate of animals. Linagliptin significantly elevated the levels of striatal DA and active
glucagon‑like peptide 1 in brain homogenate of animals. Furthermore, linagliptin amended alterations
induced by rotenone in the thiobarbituric acid reactive substances and inflammatory marker such as
tumor necrosis factor‑α level. The results of the present study indicate the neuroprotective potential
of linagliptin for the management of PD might be due to remarkable improvement in motor functions,
antioxidant, anti‑inflammatory, anti‑apoptotic, and neuroprotective mechanisms.