Pentamidine, an inhibitor of spinal flexor reflexes in rats, is a potent N-methyl-D-aspartate (NMDA) antagonist in vivo.
The present study examined whether the antimicrobial agent pentamidine exerts an antagonistic action at the N-methyl-D-aspartate (NMDA) receptor as tested on spinal reflexes in rats in vivo. After intrathecal injection both the specific NMDA antagonist (-)-2-amino-7-phosphonoheptanoate and pentamidine dose-dependently reduced the magnitude of the polysynaptic flexor reflex without affecting the monosynaptic H-reflex. In contrast, the non-NMDA antagonist 6,7-dinitroquinoxaline-2,3-dione depressed the H-reflex in a dose-dependent manner without affecting the flexor reflex. The depressant effect of pentamidine on the flexor reflex was prevented by coadministration with NMDA but not with the non-NMDA agonist alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid. These data suggest that pentamidine exerts an antagonistic action at the NMDA receptor in vivo.
Block
F
F
Department of Neurology, University of Essen, FRG.
Schmitt
T
T
Schwarz
M
M
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives*; D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D004347:Drug Interactions; D004576:Electromyography; D006181:H-Reflex / Q000187:drug effects*; D007051:Ibotenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D007278:Injections, Spinal; D008297:Male; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010419:Pentamidine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012026:Reflex, Stretch / Q000187:drug effects*; D013979:Tibial Nerve / Q000502:physiology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
D000596:Amino Acids; D011810:Quinoxalines; D016194:Receptors, N-Methyl-D-Aspartate; D007051:Ibotenic Acid; C056723:FG 9041; D016202:N-Methylaspartate; D010419:Pentamidine; D015763:2-Amino-5-phosphonovalerate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; C031231:2-amino-7-phosphonoheptanoic acid