Jurson P A, Freed W J
Neuropsychiatry Branch NIMH Neuroscience Center, Saint Elizabeths, Washington, DC 20032.
Pharmacol Biochem Behav. 1990 May;36(1):177-81. doi: 10.1016/0091-3057(90)90145-8.
CNQX and DNQX are compounds that have recently been reported to show potent non-NMDA excitatory amino acid receptor antagonist activity. Effects of these compounds on seizures induced by homocysteine thiolactone and quisqualic acid were studied in order to examine the pharmacological properties of these compounds. In a dosage of 1.16 micrograms intracerebroventricularly (ICV), CNQX prolonged the latency to the onset of quisqualate-, but not homocysteine-induced seizures. DNQX was not effective when given either ICV or systemically, although a 3.78 micrograms dose of DNQX given ICV markedly increased the variability in latency to seizure onset, suggesting a combination of pro- and anticonvulsant effects. Higher dosages of both CNQX and DNQX induced seizure-like activity after ICV injection. These data confirm that CNQX has pharmacological effects corresponding to its effects on cellular responses to quisqualate and kainate agonists, but these effects are weak and may limit its usefulness as a pharmacological tool.
CNQX和DNQX是最近报道显示出强效非NMDA兴奋性氨基酸受体拮抗剂活性的化合物。研究了这些化合物对同型半胱氨酸硫内酯和喹啉酸诱发癫痫发作的影响,以考察这些化合物的药理特性。脑室内注射(ICV)剂量为1.16微克时,CNQX延长了喹啉酸诱发癫痫发作的潜伏期,但对同型半胱氨酸诱发的癫痫发作潜伏期无延长作用。脑室内或全身给药时,DNQX均无效,尽管脑室内注射3.78微克剂量的DNQX显著增加了癫痫发作潜伏期的变异性,提示其兼具促惊厥和抗惊厥作用。脑室内注射更高剂量的CNQX和DNQX后均诱发癫痫样活动。这些数据证实,CNQX具有与其对喹啉酸和海人藻酸激动剂的细胞反应作用相对应的药理作用,但这些作用较弱,可能会限制其作为一种药理工具的用途。