Catalepsy induced by calcium channel blockers in mice.
It is known that calcium channel blockers induce Parkinsonism. In this study, amlodipine-, diltiazem-, and verapamil-induced catalepsy was investigated in mice. All of these three calcium channel blockers induced catalepsy. Dopamine D1, D2, and mACh receptor occupancies were estimated under the same conditions, and the affinities of these drugs for each receptor were also estimated in vitro. Intensity of catalepsy was predicted by dopamine D1, D2, and mACh receptor occupancies with the dynamic model which had already been constructed and was compared with the observed values. The predicted and the observed values were comparable (r = 0.98, p < 0.001). In conclusion, the dynamic model considering D1, and D2, and mACh receptor occupancy may be useful for quantitative prediction of drug-induced catalepsy.
Haraguchi
K
K
Department of Pharmacy, University of Tokyo Hospital, Faculty of Medicine, Japan.
Ito
K
K
Kotaki
H
H
Sawada
Y
Y
Iga
T
T
D017311:Amlodipine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D002375:Catalepsy / Q000139:chemically induced* / Q000188:drug therapy; D004095:Dihydropyridines / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D004110:Diltiazem / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D004195:Disease Models, Animal; D005444:Flunarizine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D008297:Male; D051379:Mice; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000627:therapeutic use; D009578:Nitrobenzenes; D010879:Piperazines; D011237:Predictive Value of Tests; D011950:Receptors, Cholinergic / Q000187:drug effects; D017447:Receptors, Dopamine D1 / Q000187:drug effects; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D012601:Scopolamine / Q000008:administration & dosage / Q000627:therapeutic use; D013997:Time Factors; D014700:Verapamil / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D018727:Muscarinic Antagonists; D009578:Nitrobenzenes; D010879:Piperazines; D011950:Receptors, Cholinergic; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D017311:Amlodipine; C054218:manidipine; D014700:Verapamil; D012601:Scopolamine; D004110:Diltiazem; D005444:Flunarizine