L-DOPA cyclohexyl ester is a novel potent and relatively stable competitive antagonist against L-DOPA among several L-DOPA ester compounds.
L-DOPA cyclohexyl ester is a novel potent and relatively stable competitive antagonist against L-DOPA among several L-DOPA ester compounds.
复制标题
L-DOPA环己酯是多种L-DOPA酯类化合物中一种新型的有效且相对稳定的L-DOPA竞争性拮抗剂。
DOI：
--
复制
发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Y. Misu
中科院分区：
文献类型：
--
作者：
N. Furukawa;Y. Goshima;T. Miyamae;Y. Sugiyama;M. Shimizu;E. Ohshima;F. Suzuki;N. Arai;K. Fujita;Y. Misu
我们探索了具有化学庞大结构的L-DOPA酯，以找到与DOPA甲酯（DOPA ME）相比的针对L-DOPA的有效稳定的竞争性拮抗剂。在麻醉大鼠孤束核降压部位注射1 μ g多巴环己酯（DOPA CHE）、多巴环戊酯（DOPA CPE）和多巴环戊二甲酯（DOPA CPDME），与多巴ME相比，对60 ng L-DOPA引起的降压反应有更明显的拮抗作用，其中以100 ng DOPA CHE的拮抗作用最强。在1 μ g时，DOPA CHE的拮抗活性持续时间大约是DOPA ME的3倍。在脑桥核的微透析过程中，从通过探针灌注的1 μ M的DOPA CHE到细胞外L-DOPA的转化在这些化合物中是最低的，并且小于DOPA ME的转化的一半。结合研究表明，L-DOPA的识别位点不同于离子型多巴胺能，多巴胺能D1和D2受体。我们最近发现，短暂性脑缺血引起的左旋多巴可能作为一个多巴胆碱敏感的原因谷氨酸释放和神经细胞死亡。多巴CHE是最有效的、相对稳定的左旋多巴竞争性拮抗剂，是开发神经保护药物的有用母体化合物。
We explored L-DOPA esters with chemically bulky structures to find a potent stable competitive antagonist against L-DOPA, compared to DOPA methyl ester (DOPA ME). In anesthetized rats, DOPA cyclohexyl ester (DOPA CHE), DOPA cyclopentyl ester (DOPA CPE) and DOPA cyclopentyldimethyl ester (DOPA CPDME) at 1 microgram microinjected into depressor sites of the nucleus tractus solitarii elicited or tended to elicit more marked antagonism against depressor responses to 60 ng L-DOPA, compared to DOPA ME. At 100 ng, DOPA CHE elicited the most potent antagonism. At 1 microgram, duration of the antagonistic activity of DOPA CHE was approximately three times longer than that of DOPA ME. During microdialysis of the nucleus accumbens, conversion from DOPA CHE at 1 microM perfused via probes to extracellular L-DOPA was the lowest among these compounds and less than one half of that from DOPA ME. Binding studies showed that the recognition site for L-DOPA differs from ionotropic glutamatergic, dopaminergic D1 and D2 receptors. We recently found that L-DOPA evoked by transient ischemia may act as a DOPA CHE-sensitive causal factor for glutamate release and resultant neuronal cell death. DOPA CHE is the most potent, relatively stable competitive antagonist against L-DOPA and is a useful mother compound to develop neuroprotective drugs.
螺哌酮与大鼠脑膜结合的生化特性。
影响因子：
3.1
作者：
Sundermann,RH;Wooten,GF
通讯作者：
Wooten,GF