Benztropine mesylate (Benztropine methanesulfonate) is a centrally active muscarinic antagonist that has been used in the symptomatic treatment of PARKINSON DISEASE. Benztropine also inhibits the uptake of dopamine.

DAT:118 nM

At doses of 5 mg/kg and 25 mg/kg, Benztropine increases the levels of extracellular dopamine in the striatum of rats in a dose-dependent manner. A daily dose of 3 mg of Benztropine effectively improves tremor and motor scores in patients with Parkinson's disease on the Unified Parkinson's Disease Rating Scale without causing adverse effects such as leukopenia.

In HEK-293 cells treated with [3H]CFT and under the condition of 130 mM sodium ions, the D313N DAT exhibited a slight increase in the apparent equilibrium dissociation constant for Benztropine. The double mutant W84L D313N DAT showed a similar apparent equilibrium dissociation constant for Benztropine when compared to the single mutation. Benztropine inhibited MTSET-induced binding of [3H]WIN to the wild-type dopamine transporter with an EC50 of 28 μM in a concentration-dependent manner. Furthermore, Benztropine demonstrated a protection rate of 32 in the X-A342C DAT construct by shielding Cys-342 from reactivity (EC50 for inhibition of [3H]WIN (4 nM) to IC50 binding).