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

Abstract

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 microM, 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.

• Authors: H Matsuo, A Matsui, R Nasu, H Takanaga, N Inoue, F Hattori, H Ohtani, Y Sawada
• Journal: Pharmaceutical research (Pharm Res) Vol. 17 Issue 5 Pg. 565-71 (May 2000) ISSN: 0724-8741 [Print] United States
• PMID: 10888308 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antitussive Agents
• Benzilates
• Cholinergic Antagonists
• Cyclopentanes
• Mandelic Acids
• Pharmaceutical Solutions
• Receptors, Cholinergic
• Receptors, Dopamine D1
• Receptors, Dopamine D2
• etafenone
• carbetapentane
• propiverine
• Propafenone
• oxybutynin

Topics

• Animals
• Antitussive Agents (pharmacology)
• Benzilates (pharmacokinetics, toxicity)
• Catalepsy (chemically induced)
• Cholinergic Antagonists (pharmacology)
• Cyclopentanes (pharmacology)
• Male
• Mandelic Acids (pharmacology)
• Mice
• Neostriatum (drug effects, metabolism)
• Parkinson Disease, Secondary (chemically induced, physiopathology)
• Pharmaceutical Solutions
• Propafenone (analogs & derivatives, pharmacology)
• Receptors, Cholinergic (drug effects, metabolism)
• Receptors, Dopamine D1 (drug effects)
• Receptors, Dopamine D2 (drug effects)