Tsuda M, Suzuki T, Misawa M
Department of Pharmacology, School of Pharmacy, Hoshi University, Tokyo, Japan.
Neuroreport. 1997 Feb 10;8(3):603-6. doi: 10.1097/00001756-199702100-00005.
We investigated the role of the NMDA receptor complex in DMCM (methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate)-induced seizures in mice. The seizure threshold of DMCM was evaluated using an i.v. infusion technique. Pretreatment with the non-competitive NMDA receptor antagonist MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d) cycloheptan-5,10-imine maleate) or phencyclidine (PCP) significantly increased the seizure threshold for DMCM. Furthermore, the seizure threshold of DMCM was increased by intracerebroventricular (i.c.v.), but not intrathecal (i.t.), pretreatment with MK-801. Moreover, 7-chlorokynurenic acid, a glycine site antagonist, also increased the seizure threshold of DMCM, whereas ifenprodil, a non-competitive polyamine site antagonist, did not. These findings indicate that the ion-channel binding site and the glycine binding site on the NMDA receptor complex in the brain may be involved in the expression of seizures induced by DMCM.
我们研究了N-甲基-D-天冬氨酸（NMDA）受体复合物在小鼠中由6,7-二甲氧基-4-乙基-β-咔啉-3-羧酸甲酯（DMCM）诱导的癫痫发作中的作用。使用静脉输注技术评估DMCM的癫痫发作阈值。用非竞争性NMDA受体拮抗剂MK-801（(+)-5-甲基-10,11-二氢-5H-二苯并(a,d)环庚烯-5,10-亚胺马来酸盐）或苯环利定（PCP）预处理可显著提高DMCM的癫痫发作阈值。此外，通过脑室内（i.c.v.）而非鞘内（i.t.）给予MK-801预处理可提高DMCM的癫痫发作阈值。此外，甘氨酸位点拮抗剂7-氯犬尿氨酸也提高了DMCM的癫痫发作阈值，而非竞争性多胺位点拮抗剂ifenprodil则没有。这些发现表明，大脑中NMDA受体复合物上的离子通道结合位点和甘氨酸结合位点可能参与了DMCM诱导的癫痫发作的表达。
