THE EFFECT OF LIFARIZINE (RS-87476), A NOVEL SODIUM AND CALCIUM-CHANNEL MODULATOR, ON ISCHEMIC DOPAMINE DEPLETION IN THE CORPUS STRIATUM OFTHE GERBIL

1 Unilateral ligation of the right common carotid artery in the anaest hetized gerbil for 3 h caused a 62.7% decrease in ipsilateral dopamine in the corpus striatum from 1.40 (+/-0.13, n = 27) mug g-1 in the non -ischaemic hemisphere to 0.47 (+/- 0.07, n = 27) mug g-1 in the ischae mic hemisphere (all results are expressed as mean +/- s.e.mean). In sh am-operated animals there were no differences in the dopamine levels ( 1.31 +/- 0.14 mug g-1, n = 11, left; 1.27 +/- 0.13 mug g-1, n = 11 in the right hemisphere). Animals with intact communicating arteries in t he circulus arteriosus were excluded. 2 Lifarizine (RS-87476; 250, 500 , but not 50, mug kg-1, i.p.) protected against this dopamine depletio n showing only a 9.2% decrease at 250 mug kg-1, i.p. (P < 0.01) and no decrease at 500 mug kg-1, i.p. (P < 0.01). 3 Nicardipine (250 mug kg- 1, p.o.) was effective when administered chronically once daily for 10 days (26.6% decrease, P < 0.05) but not when administered acutely at 50 mug kg-1, i.p.