Effect of bimoclomol (N-[2-hydroxy-3-(l-piperidinyl)propoxy]-3 pyridine-carboximidoyl-chloride) on iminodipropionitrile-induced central effects

Dyskinesia is frequently seen in neurological disorders affecting the basal ganglia. Iminodipropionitrile (IDPN) produces a somewhat similar motor syn drome in rodents, one that is a possible model for dyskinesia. Because in p revious studies the compound (N-[2-hydroxy-3-(1-piperidinyl) propoxy]-3 pyr idine-carboximidoyl-chloride) (Bimoclomol, BRLP-4) was shown to provide pro tection against IDPN-induced retinopathy; we investigated the effect of BRL P-42 on IDPN-induced motor changes and on IDPN-induced cerebral amino acid level changes in rats and mice. IDPN had a biphasic effect on motor activit y in C57BL/6 mice: it was a depressant for 24 days and a stimulant after 30 days. Bimoclomol inhibited the motor depressant effect and enhanced the st imulatory effect of IDPN in this mouse strain. In BALB/cBy mice and Sprague -Dawley rats IDPN produced persistent vertical head movements and changes i n the level of glutamic acid in brain. Bimoclomol reduced the effect of IDP N on bead movements and blocked the effect on cerebral glutamate; by itself it had no effect on motor activity in either species. Bimoclomol inhibited ischemia-induced [H-3]norepinephrine release from rat hippocampal slices. Our findings indicate that Bimoclomol could have a beneficial effect on som e dyskinesias, and on drug-induced vertical head movements. (C) 1999 Elsevi er Science Ltd. All rights reserved.