Propiverine-induced Parkinsonism: A case report and a pharmacokinetic/pharmacodynamic study in mice

Purpose. We present a case report of propiverine-induced Parkinsonism. We previously reported the induction of catalepsy by amiodarone, aprindine and procaine, which possess a diethylaminomethyl moiety and demonstrated selective blockade of dopamine D2 receptors by these drugs in mice. We hypothesized that drugs possessing a diethylaminomethyl structure may generally induce Parkinsonism and/or catalepsy. Methods. Thus, we performed a study to examine whether oxybutynin, pentoxyverine and etafenone, as well as propiverine, induce catalepsy in mice. Results. The intensity of drug-induced catalepsy was in the order: haloperidol > etafenone > pentoxyverine > propiverine > oxybutynin. In vivo occupancy of dopamine D₁, D₂ and mACh receptors in the striatum was also examined. The in vitro binding affinities to the D₁, D₂ and mACh receptors in the striatum synaptic membrane were within the ranges of 2.4-140 μM, 380-4,200 nM, and 1.2-2,800 nM, respectively. Conclusions. These results support the idea that any drug possessing a diethylaminomethyl moiety may contribute to the induction of catalepsy, possibly by occupying dopamine receptors.