Peterson S L
Department of Medical Pharmacology and Toxicology, Texas A&M University Health Science Center, College Station 77843-1114.
Epilepsia. 1994 Sep-Oct;35(5):933-8. doi: 10.1111/j.1528-1157.1994.tb02537.x.
D-Cycloserine is a partial agonist of the strychnine-insensitive glycine site that inhibits the tonic hindlimb extension (THE) component of maximal electroshock seizures (MES). This study determined the effect of focal D-clycoserine microinfusion into nucleus reticularis pontis oralis (RPO) on the THE component of MES in rats. Bilateral microinfusion of D-cycloserine (50 nmol per side) into the RPO region 5.4 and 5.6 mm posterior to bregma inhibited THE in 80% of rats tested. Unilateral D-cycloserine (50 nmol) RPO microinfusions were ineffective. Likewise, RPO microinfusion of vehicle, L-cycloserine (50 nmol per side), or the strychnine-insensitive glycine site antagonist 7-chlorokynurenic acid (10 and 50 nmol per side) did not alter THE incidence. However, coinfusion of 7-chlorokynurenic acid (50 nmol per side) with D-cycloserine (50 nmol per side) completely antagonized the anticonvulsant activity induced by D-cycloserine (8 of 8 rats with THE). These data indicate that the anticonvulsant activity of D-cycloserine is mediated by RPO. Because the anticonvulsant effect is stereospecific and is reversible by 7-chlorokynurenic acid, these results also indicate that D-cycloserine acts through the strychnine-insensitive glycine site to inhibit THE.
D-环丝氨酸是对士的宁不敏感的甘氨酸位点的部分激动剂，可抑制最大电休克惊厥（MES）的强直性后肢伸展（THE）成分。本研究确定了向大鼠脑桥网状核嘴侧（RPO）局部微量注射D-环丝氨酸对MES的THE成分的影响。在脑桥后5.4和5.6毫米处向RPO区域双侧微量注射D-环丝氨酸（每侧50纳摩尔）可抑制80%受试大鼠的THE。单侧向RPO微量注射D-环丝氨酸（50纳摩尔）无效。同样，向RPO微量注射溶剂、L-环丝氨酸（每侧50纳摩尔）或对士的宁不敏感的甘氨酸位点拮抗剂7-氯犬尿氨酸（每侧10和50纳摩尔）不会改变THE的发生率。然而，将7-氯犬尿氨酸（每侧50纳摩尔）与D-环丝氨酸（每侧50纳摩尔）共同注射可完全拮抗D-环丝氨酸诱导的抗惊厥活性（8只大鼠中有8只出现THE）。这些数据表明，D-环丝氨酸的抗惊厥活性是由RPO介导的。由于抗惊厥作用具有立体特异性且可被7-氯犬尿氨酸逆转，这些结果还表明，D-环丝氨酸通过对士的宁不敏感的甘氨酸位点发挥作用来抑制THE。
