Catalepsy induced by manidipine, a calcium channel blocker, in mice.
Manidipine, a calcium channel blocker, is a piperazine derivative similar to flunarizine or cinnarizine, which are known to induce parkinsonism. Since it has been reported that manidipine can worsen parkinsonian symptoms in a patient with Parkinson's disease, we have evaluated catalepsy in manidipine-treated mice and compared this with flunarizine-and haloperidol-induced catalepsy. The minimum dose at which manidipine induced catalepsy was 200 times higher than that of haloperidol whereas for flunarizine, the minimum dose was 50 times higher than that for haloperidol. Manidipine, flunarizine and haloperidol occupied both dopamine D1 and D2 receptors and D2-receptor occupancy was higher than D1-receptor occupancy. These results suggest that the blockade of dopamine D1 and D2 receptors by drugs and the drug-induced catalepsy are related to the structure (piperazinyl substituent) of the drugs.
Haraguchi
K
K
Department of Pharmacy, University of Tokyo Hospital, Faculty of Medicine, University of Tokyo, Japan.
Ito
K
K
Sawada
Y
Y
Iga
T
T
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002375:Catalepsy / Q000139:chemically induced* / Q000503:physiopathology; D004095:Dihydropyridines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009578:Nitrobenzenes; D010276:Parasympatholytics / Q000494:pharmacology; D010879:Piperazines; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism; D012601:Scopolamine / Q000494:pharmacology
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D009578:Nitrobenzenes; D010276:Parasympatholytics; D010879:Piperazines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C054218:manidipine; D012601:Scopolamine