EFFECTS OF THE NOVEL TRICYCLIC QUINOXALINEDIONE DERIVATIVES, SM-18400AND ITS ANALOGS, ON N-METHYL-D-ASPARTATE (NMDA) RECEPTOR-MEDIATED SYNAPTIC TRANSMISSION IN THE ISOLATED NEONATAL RAT SPINAL-CORD IN-VITRO
Y. Maruoka et al., EFFECTS OF THE NOVEL TRICYCLIC QUINOXALINEDIONE DERIVATIVES, SM-18400AND ITS ANALOGS, ON N-METHYL-D-ASPARTATE (NMDA) RECEPTOR-MEDIATED SYNAPTIC TRANSMISSION IN THE ISOLATED NEONATAL RAT SPINAL-CORD IN-VITRO, Japanese Journal of Pharmacology, 76(3), 1998, pp. 265-270
We examined the effects of novel tricyclic quinoxalinedione derivative
s, SM-18400 ((S)-9-chloro-5-[p-aminomethyl-o-(carboxymethoxy) ihydro-1
H,5H-pyrido[1,2,3-de]quinoxaline-2,3-dione hydrochloride trihydrate) a
nd its analogs (i.e., ID-17263 and ID-17332), on the N-methyl-D-aspart
ate (NMDA) receptor-mediated polysynaptic reflex (PSR) in the isolated
spinal cord of neonatal rats in vitro. Application of SM-18400 select
ively suppressed the PSR activity in a concentration-dependent manner
without affecting the monosynaptic reflex (MSR). Differential suppress
ion of the PSR was also obtained with ID-17263, ID-17332 and other kno
wn NMDA receptor glycine-binding site antagonists,5,7-dichlorokynurena
te (5,7-diClkyn) and L-689,560 lamino-carbonylamino-1,2,3,4-tetrahydro
quinoline). Relative potencies of the test drugs for inhibition of the
PSR were as follows: SM-18400 much greater than L-689,560 > ID-17332
> ID-17263 > 5,7-diClkyn. In addition, the inhibitory effects of SM-18
400 on PSR were markedly antagonized by simultaneous application of D-
serine, and agonist for NMDA receptor glycine-binding sites. These fin
dings suggest that SM-18400 is a potent NMDA receptor glycine-binding
site antagonist and blocks the NMDA receptor-mediated synaptic neurotr
ansmission in the spinal cord in vitro.