PT  - JOURNAL ARTICLE
AU  - Akiko Matsui
AU  - Hirotami Matsuo
AU  - Hitomi Takanaga
AU  - Shigeki Sasaki
AU  - Minoru Maeda
AU  - Yasufumi Sawada
TI  - Prediction of Catalepsies Induced by Amiodarone, Aprindine and Procaine: Similarity in Conformation of Diethylaminoethyl Side Chain
DP  - 1998 Nov 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 725--732
VI  - 287
IP  - 2
4099  - http://jpet.aspetjournals.org/content/287/2/725.short
4100  - http://jpet.aspetjournals.org/content/287/2/725.full
SO  - J Pharmacol Exp Ther1998 Nov 01; 287
AB  - Recently, clinical cases of parkinsonism due to antiarrhythmics drugs amiodarone and aprindine and a local anesthetic drug procaine have been reported. We performed both in vivo and in vitro experiments to quantitatively predict the intensity of catalepsy by these drugs and haloperidol in mice. Haloperidol showed the most potent relative intensity of catalepsy, followed by aprindine, metoclopramide, tiapride, amiodarone and procaine, in that order.In vivo dopamine D1 and D2receptor occupancies of the six drugs to the striatum were observed.In vitro binding affinity (Ki) of these drugs to the D1 and D2 receptors in the striatum synaptic membrane was within the range of 60 nM to 706 μM, 0.5 nM to 75 μM and 860 nM to 115 μM, respectively. A good correlation between the relative intensity of drug-induced catalepsy and theKi values for the dopamine D1 and D2 receptors was obtained (r = .911 and r = .896, respectively; P < .05). The partial tertiary structure of the tested drugs was well superimposed on that of haloperidol. In conclusion, these drug-induced catalepsies were due to the blockade of the D1 and D2 receptors, which was related to the analogous tertiary structures (diethylaminoethyl side chain). The American Society for Pharmacology and Experimental Therapeutics