Macdonald R L, Barker J L
Neurology. 1979 Apr;29(4):432-47. doi: 10.1212/wnl.29.4.432.
Mammalian spinal cord neurons were grown in dissociated cell culture and used to study the effects of the anticonvulsant barbiturates phenobarbital and mephobarbital, and the anesthetic barbiturates pentobarbital, secobarbital, and 1,3-dimethyl-butylethyl barbituric acid on amino acid responses and neuronal membrane properties. All barbiturates augmented responses to GABA and diminished glutamate (GLU) responses, but the anesthetic barbiturates were more potent. The anesthetic barbiturates directly depressed excitability by increasing membrane conductance, an effect reversed by the GABA antagonists picrotoxin and penicillin. Anticonvulsant barbiturates, however, had only minimal GABA-mimetic inhibitory action at high doses. Modulation of synaptic events mediated by GABA and GLU might contribute to barbiturate anticonvulsant activity; and direct GABA-mimetic inhibition, combined with similar modulation of synaptic transmission, might underlie barbiturate anesthesia.
将哺乳动物脊髓神经元培养于解离细胞培养物中，用于研究抗惊厥巴比妥类药物苯巴比妥和甲丙氨酯，以及麻醉性巴比妥类药物戊巴比妥、司可巴比妥和1,3 - 二甲基 - 丁基乙基巴比妥酸对氨基酸反应和神经元膜特性的影响。所有巴比妥类药物均增强了对γ-氨基丁酸（GABA）的反应并减弱了谷氨酸（GLU）反应，但麻醉性巴比妥类药物作用更强。麻醉性巴比妥类药物通过增加膜电导直接降低兴奋性，该效应可被GABA拮抗剂苦味毒和青霉素逆转。然而，抗惊厥巴比妥类药物在高剂量时仅具有最小的GABA模拟抑制作用。由GABA和GLU介导的突触事件的调节可能有助于巴比妥类药物的抗惊厥活性；直接的GABA模拟抑制作用，结合对突触传递的类似调节，可能是巴比妥类麻醉的基础。
