Propiverine-induced Parkinsonism: a case report and a pharmacokinetic/pharmacodynamic study in mice.
OBJECTIVE
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.
Matsuo
H
H
Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Matsui
A
A
Nasu
R
R
Takanaga
H
H
Inoue
N
N
Hattori
F
F
Ohtani
H
H
Sawada
Y
Y
D000818:Animals; D000996:Antitussive Agents / Q000494:pharmacology; D001561:Benzilates / Q000493:pharmacokinetics / Q000633:toxicity*; D002375:Catalepsy / Q000139:chemically induced; D018680:Cholinergic Antagonists / Q000494:pharmacology; D003517:Cyclopentanes / Q000494:pharmacology; D008297:Male; D008333:Mandelic Acids / Q000494:pharmacology; D051379:Mice; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D010302:Parkinson Disease, Secondary / Q000139:chemically induced* / Q000503:physiopathology; D019999:Pharmaceutical Solutions; D011405:Propafenone / Q000031:analogs & derivatives / Q000494:pharmacology; D011950:Receptors, Cholinergic / Q000187:drug effects / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000187:drug effects; D017448:Receptors, Dopamine D2 / Q000187:drug effects
D000996:Antitussive Agents; D001561:Benzilates; D018680:Cholinergic Antagonists; D003517:Cyclopentanes; D008333:Mandelic Acids; D019999:Pharmaceutical Solutions; D011950:Receptors, Cholinergic; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C001162:etafenone; C018861:carbetapentane; C015586:propiverine; D011405:Propafenone; C005419:oxybutynin