INTERACTION BETWEEN ENANTIOMERS OF MIANSERIN AND ORG3770 AT 5-HT3, RECEPTORS IN CULTURED MOUSE NEUROBLASTOMA-CELLS
INTERACTION BETWEEN ENANTIOMERS OF MIANSERIN AND ORG3770 AT 5-HT3, RECEPTORS IN CULTURED MOUSE NEUROBLASTOMA-CELLS
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DOI：
10.1016/0028-3908(94)90081-7
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发表时间：
1994-03-01
影响因子：
4.7
通讯作者：
VIJVERBERG, HPM
中科院分区：
文献类型：
--
作者：
KOOYMAN, AR;ZWART, R;VIJVERBERG, HPM
通过放射配体结合和全细胞电压箝位实验研究了米安色林和ORG3770对小鼠神经母细胞瘤N1E-115细胞血清素5-HT3受体的立体选择性作用。在N1E-115细胞匀浆中，[H-3]GR65630与5-HT3识别位点的特异性结合被米安色林和ORG3770及其对映体降低。米安色林和ORG3770的强效(R)对映体pK(i)值分别为8.44和8.62。米安色林和ORG3770的(R)对映体比各自的(S)对映体强15倍和37倍。外消旋体的效力仅为对应(R)对映体的1.9倍和3.3倍。在电压箝位实验中，(R)对映体用pIC（?）阻断5-羟色胺（5-HT）诱导的离子电流。（50）， (R)米安色林的值为8.52,(R) ORG3770对映体的值为8.26。米安色林和ORG3770的(R)对映体阻断5- ht诱导的离子电流的能力是其(S)对映体的24倍和145倍。外消旋体的效力比对应的(R)对映体低6倍和13倍。此外，低浓度的(S)对映体部分逆转了ORG3770 (R)对映体对5- ht离子电流的阻断作用。结果表明，这两种对映体以相互依赖的方式阻断5-HT3受体介导的离子电流。
Stereoselective effects of mianserin and ORG3770 on serotonin 5-HT3 receptors in mouse neuroblastoma N1E-115 cells have been investigated in radioligand binding and in whole-cell voltage clamp experiments. The specific binding of [H-3]GR65630 to 5-HT3 recognition sites in N1E-115 cell homogenates is reduced by mianserin and ORG3770 and their enantiomers. The pK(i) values of the more potent (R)enantiomers of mianserin and ORG3770 are 8.44 and 8.62, respectively. The (R)enantiomers of mianserin and ORG3770 are 15 and 37 times more potent than their respective (S)enantiomers. The racemates are only 1.9 and 3.3 times less potent than the corresponding (R)enantiomers. In voltage clamp experiments the (R)enantiomers block the 5-hydroxytryptamine(5-HT)-induced ion current with pIC(?)(50) values of 8.52 for (R)mianserin and 8.26 for the (R)enantiomer of ORG3770. The (R)enantiomers of mianserin and ORG3770 are 24 and 145 times more potent in blocking the 5-HT-induced ion current than their respective (S)enantiomers. The racemates are 6 and 13 times less potent than the corresponding (R)enantiomers. In addition, the block of 5-HT-induced ion current by the (R)enantiomer of ORG3770 is partially reversed by a low concentration of its (S)enantiomer. The results indicate that the two enantiomers block the 5-HT3 receptor-mediated ion current in a mutually dependent manner.