Alexander C B, Ellmore T M, Kokate T G, Kirkby R D
Neuronal Excitability Section, Epilepsy Research Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1408, USA.
Eur J Pharmacol. 1998 Feb 26;344(1):15-25. doi: 10.1016/s0014-2999(97)01551-3.
We confirmed that the effects of inhibitors of nitric oxide (NO) synthase, such as Nomega-nitro-L-arginine methyl ester and Nomega-nitro-L-arginine, differ depending on several experimental factors. Both compounds but not their less active enantiomers delayed picrotoxin-induced clonus in mice yet increased the incidence of clonus following low-dose picrotoxin. Nomega-nitro-L-arginine methyl ester significantly reduced the latencies of both myoclonus and clonus in older but not younger Sprague-Dawley rats receiving pentylenetetrazol s.c. By contrast, there was no significant change in the latencies for myoclonus and clonus in Wistar rats (older and younger). However, when pentylenetetrazol was administered i.p. rather than s.c., Nomega-nitro-L-arginine methyl ester dramatically increased latencies of convulsive indicators, including tonus, in both Sprague-Dawley and Wistar rats. Nomega-nitro-L-arginine methyl ester also delayed tonus but not myoclonus or clonus in mice, regardless of the systemic route of administration of pentylenetetrazol. Both Nomega-nitro-L-arginine methyl ester and NG-nitro-L-arginine increased the tonic CD50 of pentylenetetrazol in mice and Nomega-nitro-L-arginine methyl ester delayed 4-aminopyridine-induced tonus. However, Nomega-nitro-L-arginine methyl ester reduced the tonic CD50 of both picrotoxin and 4-aminopyridine in mice and failed to suppress tonus following maximal electroshock. Evidently, inhibitors of NO synthase are not universally effective antitonic drugs.
我们证实，一氧化氮（NO）合酶抑制剂的作用，如Nω-硝基-L-精氨酸甲酯和Nω-硝基-L-精氨酸，会因几个实验因素而有所不同。这两种化合物而非其活性较低的对映体，可延迟小鼠中匹鲁卡品诱导的阵挛，但会增加低剂量匹鲁卡品后阵挛的发生率。Nω-硝基-L-精氨酸甲酯显著缩短了接受皮下注射戊四氮的老年而非年轻的斯普拉格-道利大鼠的肌阵挛和阵挛潜伏期。相比之下，Wistar大鼠（老年和年轻）的肌阵挛和阵挛潜伏期没有显著变化。然而，当戊四氮经腹腔注射而非皮下注射时，Nω-硝基-L-精氨酸甲酯显著增加了斯普拉格-道利大鼠和Wistar大鼠惊厥指标（包括紧张度）的潜伏期。无论戊四氮的全身给药途径如何，Nω-硝基-L-精氨酸甲酯也会延迟小鼠的紧张度，但不会延迟肌阵挛或阵挛。Nω-硝基-L-精氨酸甲酯和NG-硝基-L-精氨酸均增加了小鼠中戊四氮的强直CD50，且Nω-硝基-L-精氨酸甲酯延迟了4-氨基吡啶诱导的紧张度。然而，Nω-硝基-L-精氨酸甲酯降低了小鼠中匹鲁卡品和4-氨基吡啶的强直CD50，并且在最大电休克后未能抑制紧张度。显然，NO合酶抑制剂并非普遍有效的抗强直药物。
