Effect of eliprodil, an NMDA receptor antagonist acting at the polyamine modulatory site, on local cerebral glucose use in the rat in the rat brain.
The present investigation examined the effect of eliprodil, an atypical NMDA receptor antagonist that acts at the polyamine modulatory site, on local cerebral glucose utilization using the quantitative autoradiographic 2-[14C]deoxyglucose method in the conscious rat. Eliprodil, at doses of 3, 10 and 30 mg/kg i.p., did not increase cerebral glucose use in any of the 82 different brain regions studied. However, in some of the regions examined, local cerebral glucose utilization was slightly reduced, the most pronounced decreases being measured in some extrapyramidal, sensorimotor and limbic areas (dentate gyrus, septum, lateral habenula, amygdala). This decrease in glucose utilization was dose-dependent: no significant change was noted after 3 mg/kg i.p. of eliprodil, while 18 (at 10 mg/kg, i.p.) and 29 (at 30 mg/kg, i.p.) regions displayed a moderate (20-25%) though significant decrease in glucose use. These data demonstrate that the pattern of alterations in glucose use produced by eliprodil is different from that induced by NMDA channel blockers or competitive NMDA receptor antagonists. The fact that blockade of the polyamine modulatory site is not associated with an activation of specific limbic circuits may explain why, at neuroprotective doses, eliprodil is devoid of those unwanted side effects (including intrinsic neurotoxicity on cortical neurons) associated with NMDA channel blockers.
Cudennec
A
A
Synthelabo Recherche, Preclinical Research Department, Bagneux, France.
Duverger
D
D
Benavides
J
J
Scatton
B
B
Nowicki
J P
JP
D000818:Animals; D015317:Biogenic Polyamines / Q000502:physiology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D008297:Male; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D015317:Biogenic Polyamines; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D005947:Glucose; C058083:eliprodil