J. Jolkkonen et al., Neuroprotection by the alpha(2)-adrenoceptor agonist, dexmedetomidine, in rat focal cerebral ischemia, EUR J PHARM, 372(1), 1999, pp. 31-36
The present study was undertaken to explore the possible neuroprotective ef
fect of the selective alpha(2)-adrenoceptor agonist, dexmedetomidine in a r
at model of focal cerebral ischemia. The effect of dexmedetomidine (9 mu g
kg(-1)) on infarct volume was assessed and compared to that of glutamate re
ceptor antagonists cis-4(phosphonomethyl)-2-piperidine carboxylic acid (CGS
-19755) (20 mg kg(-1)) or 2,3-dihydro-6-nitro-7-sulfamoyl-benzo(F)quinoxali
ne (NBQX) (50 mg kg(-1)). Dexmedetomidine decreased total ischemic volume b
y 40% in the cortex (P < 0.05) compared to NaCl-treated control rats, where
as NBQX reduced the infarct by 73% in the cortex (P < 0.001) and by 43% in
the striatum (P < 0.01). Dexmedetomidine infusion was associated with some
minor degree of hyperglycemia and hypotension Drug-induced kidney changes w
ere only seen in NBQX-treated rats. These results suggest that dexmedelomid
ine reduced ischemic volume despite causing a minor increase in blood gluco
se concentrations and hypotension. Its neuroprotective efficacy was better
than that produced by CGS-19775, and dexmedetomidine was safer with respect
to kidney toxicity when compared to NBQX. (C) 1999 Elsevier Science B.V. A
ll rights reserved.