PREDICTION OF CATALEPSIES INDUCED BY AMIODARONE, APRINDINE AND PROCAINE - SIMILARITY IN CONFORMATION OF DIETHYLAMINOETHYL SIDE-CHAIN

Recently, clinical cases of parkinsonism due to antiarrhythmics drugs amiodarone and aprindine and a local anesthetic drug procaine have bee n reported. We performed both in vivo and in vitro experiments to quan titatively predict the intensity of catalepsy by these drugs and halop eridol in mice. Haloperidol showed the most potent relative intensity of catalepsy, followed by aprindine, metoclopramide, tiapride, amiodar one and procaine, in that order. In vivo dopamine D-1 and D-2 receptor occupancies of the six drugs to the striatum were observed. In vitro binding affinity (K-i) of these drugs to the D-1 and D-2 receptors in the striatum synaptic membrane was within the range of 60 nM to 706 mu M, 0.5 nM to 75 mu M and 860 nM to 115 mu M, respectively. A good cor relation between the relative intensity of drug-induced catalepsy and the K-i values for the dopamine D-1 and D-2 receptors was obtained (r = .911 and r = .896, respectively; P < .05). The partial tertiary stru cture of the tested drugs was well superimposed on that of haloperidol . In conclusion, these drug-induced catalepsies were due to the blocka de of the D-1 and D-2 receptors, which was related to the analogous te rtiary structures (diethylaminoethyl side chain).