The effect of lifarizine (RS-87476), a novel sodium and calcium channel modulator, on ischaemic dopamine depletion in the corpus striatum of the gerbil.
1. Unilateral ligation of the right common carotid artery in the anaesthetized gerbil for 3 h caused a 62.7% decrease in ipsilateral dopamine in the corpus striatum from 1.40 (+/- 0.13, n = 27) micrograms g-1 in the non-ischaemic hemisphere to 0.47 (+/- 0.07, n = 27) micrograms g-1 in the ischaemic hemisphere (all results are expressed as mean +/- s.e. mean). In sham-operated animals there were no differences in the dopamine levels (1.31 +/- 0.14 micrograms g-1, n = 11, left; 1.27 +/- 0.13 micrograms g-1, n = 11 in the right hemisphere). Animals with intact communicating arteries in the circulus arteriosus were excluded. 2. Lifarizine (RS-87476; 250, 500, but not 50, micrograms kg-1, i.p.) protected against this dopamine depletion showing only a 9.2% decrease at 250 micrograms kg-1, i.p. (P < 0.01) and no decrease at 500 micrograms kg-1, i.p. (P < 0.01). 3. Nicardipine (250 micrograms 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 micrograms kg-1, i.p.
Syntex Research Centre, Riccarton, Edinburgh.
C M
CM
Brown
C
C
Calder
B J
BJ
Alps
M
M
Spedding
D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002339:Carotid Arteries / Q000502:physiology; D002561:Cerebrovascular Disorders / Q000503:physiopathology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D005849:Gerbillinae; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D009529:Nicardipine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D015222:Sodium Channels / Q000187:drug effects*
D002121:Calcium Channel Blockers; D007093:Imidazoles; D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D015222:Sodium Channels; C067927:lifarizine; D009529:Nicardipine; D004298:Dopamine