Hemrick-Luecke S K, Fuller R W
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA.
Eur J Pharmacol. 1996 Sep 12;311(2-3):207-11. doi: 10.1016/0014-2999(96)00439-6.
The possible involvement of 5-HT2A or 5-HT2C receptors in the elevation of serum corticosterone in rats by quipazine (2-(1-piperazinyl)quinoline maleate) and MK-212 (6-chloro-(1-piperazinyl)pyrazine), direct-acting 5-HT receptor agonists, was investigated by the use of two newly available receptor antagonists, SB 200646A (N-(1-methyl-5-indolyl)-N'-(3-pyridyl)urea) and MDL 100,907 (R-(+)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenylethyl)]- 4-piperidinemethanol). MDL 100,907 blocked the increase in serum corticosterone elicited by quipazine and MK-212 with ED50 values of 0.0028 and 0.0027 mg/kg, s.c., respectively. In contrast, SB 200646A only partially antagonized the serum corticosterone concentration increases by quipazine and MK-212 even at the highest dose tested, 40 mg/kg, i.p. Because published data show the affinities of MDL 100,907 and SB 200646A for 5-HT2C receptors to be nearly identical, whereas the affinity of MDL 100,907 for 5-HT2A receptors is 17500-fold higher than that of SB 200646A, our findings suggest that 5-HT2A receptors rather than 5-HT2C receptors mediate the serum corticosterone increases by both quipazine and MK-212.
通过使用两种新获得的受体拮抗剂SB 200646A（N-（1-甲基-5-吲哚基）-N'-（3-吡啶基）脲）和MDL 100,907（R-（+）-α-（2,3-二甲氧基苯基）-1-[2-（4-氟苯基）乙基]-4-哌啶甲醇），研究了5-HT2A或5-HT2C受体在直接作用的5-羟色胺（5-HT）受体激动剂喹哌嗪（2-（1-哌嗪基）喹啉马来酸盐）和MK-212（6-氯-（1-哌嗪基）吡嗪）引起的大鼠血清皮质酮升高过程中可能的参与情况。MDL 100,907阻断了喹哌嗪和MK-212引起的血清皮质酮升高，皮下注射时的ED50值分别为0.0028和0.0027 mg/kg。相比之下，即使在腹腔注射最高测试剂量40 mg/kg时，SB 200646A也只能部分拮抗喹哌嗪和MK-212引起的血清皮质酮浓度升高。因为已发表的数据表明MDL 100,907和SB 200646A对5-HT2C受体的亲和力几乎相同，而MDL 100,907对5-HT2A受体的亲和力比SB 200646A高17500倍，所以我们的研究结果表明，5-HT2A受体而非5-HT2C受体介导了喹哌嗪和MK-212引起的血清皮质酮升高。
