Effect of bimoclomol (N-[2-hydroxy-3-(1-piperidinyl) propoxy]-3 pyridine-carboximidoyl-chloride) on iminodipropionitrile-induced central effects

Abstract

Dyskinesia is frequently seen in neurological disorders affecting the basal ganglia. Iminodipropionitrile (IDPN) produces a somewhat similar motor syndrome in rodents, one that is a possible model for dyskinesia. Because in previous studies the compound (N- 2-hydroxy-3-(1-piperidinyl) propoxy -3 pyridine-carboximidoyl-chloride) (Bimoclomol, BRLP-42) was shown to provide pro- tection against IDPN-induced retinopathy; we investigated the effect of BRLP-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 activity 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 stimulatory effect of IDPN in this mouse strain. In BALB/cBy mice and Sprague Dawley rats IDPN produced persistent vertical head movements and changes in the level of glutamic acid in brain. Bimoclomol reduced the effect of IDPN on head movements and blocked the effect on cerebral glutamate; by itself it had no effect on motor activity in either species. Bimoclomol inhibited ischemia-induced [ 3H] norepinephrine release from rat hippocampal slices. Our findings indicate that Bimoclomol could have a beneficial effect on some dyskinesias, and on drug-induced vertical head movements.