Pharmacological characterization of non‐NMDA subtypes of glutamate receptor in the neonatal rat hemisected spinal cord in vitro

1 A grease‐gap technique was used to record depolarizing responses to α‐amino‐3‐hydroxy‐5‐methyl‐isoxazole‐4‐propionate (AMPA), kainate and N‐methyl‐ d ‐aspartate (NMDA) in the hemisected spinal cord of the neonatal rat. The pharmacology of non‐NMDA subtypes of glutamate receptor was investigated with the novel quinoxalinedione, 2,3‐dihydroxy‐6‐nitro‐7‐sulphamoyl‐benzo (F)‐quinoxaline (NBQX) and with a series of barbiturates. 2 NBQX antagonized AMPA‐ and kainate‐, but not NMDA‐ induced depolarizations. The near parallel shifts of the major part of the dose‐response curves for AMPA and kainate by NBQX gave pA 2 values (± s.e.) of 6.7 ± 0.2 and 6.8 ± 0.2 respectively, consistent with a common site of action for these two agonists. 3 Below the 50% level at which these pA 2 values were calculated, however, an NBQX‐resistant plateau was seen within the kainate, but not the AMPA, dose‐response curve. 4 In decreasing order of potency, methohexitone, secobarbitone, thiopentone, pentobarbitone and phenobarbitone preferentially reduced kainate‐, rather than AMPA‐ and NMDA‐, induced depolarizations. Methohexitone was also the most selective with IC 50 s against kainate, AMPA and NMDA of 31 ± 7, 172 ± 47 and >200 μ m respectively. 5 The NBQX‐resistant plateau seen within the kainate dose‐response curve was reduced by methohexitone. Kainate antagonism by methohexitone was not reduced by 50 μ m picrotoxin. 6 We conclude that, while mixed agonist actions may hamper demonstration of antagonist selectivity, depolarizations induced by the non‐NMDA ionotropic agonists, AMPA and kainate, are mediated in part via distinct receptors.