Starr M S, Starr B S
Department of Pharmacology, School of Pharmacy, London, UK.
Pharmacol Biochem Behav. 1993 Jun;45(2):321-5. doi: 10.1016/0091-3057(93)90246-p.
The sensitivity of pilocarpine-induced seizures to NMDA receptor blockade with MK-801, or to inhibition of synthesis of the second messenger nitric oxide (NO) with N omega-nitro-L-arginine methyl ester (L-NAME), was studied in mice. The NO precursor L-arginine (100-500 mg/kg, IP) and L-NAME (1-125 mg/kg, IP) had no overt effects on animals' behaviour by themselves, while MK-801 (0.1-0.8 mg/kg, IP) caused motor excitability at low doses and sedation and paraplegia at high ones. Contrary to expectation, MK-801 and L-NAME failed to protect mice against limbic motor seizures induced by pilocarpine (400 mg/kg, IP), and L-arginine was not proconvulsant in mice challenged with a threshold convulsant dose of the cholinomimetic (100 mg/kg, IP). Surprisingly, both MK-801 and L-NAME were found to be proconvulsant when injected in conjunction with 100 mg/kg pilocarpine, and in both cases this convulsant action synergised with that produced by the dopamine D1 agonist SK&F38393 (10 mg/kg, IP). Concomitant administration of L-arginine (500 mg/kg) prevented the convulsant effect of 5 mg/kg L-NAME but was ineffective against 25 mg/kg L-NAME and MK-801. It is concluded that glutamate, acting through the NMDA receptor and NO production, normally suppresses epileptogenesis in the mouse pilocarpine model of limbic epilepsy.
在小鼠中研究了毛果芸香碱诱发的癫痫发作对NMDA受体拮抗剂MK-801或一氧化氮（NO）合成抑制剂Nω-硝基-L-精氨酸甲酯（L-NAME）的敏感性。NO前体L-精氨酸（100 - 500mg/kg，腹腔注射）和L-NAME（1 - 125mg/kg，腹腔注射）单独对动物行为无明显影响，而MK-801（0.1 - 0.8mg/kg，腹腔注射）在低剂量时引起运动兴奋性，高剂量时导致镇静和截瘫。与预期相反，MK-801和L-NAME未能保护小鼠免受毛果芸香碱（400mg/kg，腹腔注射）诱发的边缘性运动性癫痫发作，并且L-精氨酸对用阈剂量拟胆碱药（100mg/kg，腹腔注射）攻击的小鼠没有惊厥作用。令人惊讶的是，当与100mg/kg毛果芸香碱联合注射时，MK-801和L-NAME均被发现具有惊厥作用，并且在这两种情况下，这种惊厥作用都与多巴胺D1激动剂SK&F38393（10mg/kg，腹腔注射）产生的惊厥作用协同。同时给予L-精氨酸（500mg/kg）可预防5mg/kg L-NAME的惊厥作用，但对25mg/kg L-NAME和MK-801无效。得出的结论是，谷氨酸通过NMDA受体和NO生成起作用，通常在小鼠边缘性癫痫的毛果芸香碱模型中抑制癫痫发生。
