A potential 5-HT1A receptor antagonist: p-MPPI.
A potential 5-HT1A receptor antagonist: p-MPPI.
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DOI：
10.1016/0024-3205(94)00686-5
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发表时间：
1994
期刊：
影响因子：
6.1
通讯作者：
H. Kung;M. Kung;W. Clarke;S. Maayani;Z. Zhuang
中科院分区：
文献类型：
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作者：
H. Kung;M. Kung;W. Clarke;S. Maayani;Z. Zhuang
开发了一种潜在的 5-HT1A 受体拮抗剂 p-MPPI，4-(2'-甲氧基-)苯基-1-[2'-(n-2“-吡啶基)-p-碘苯甲酰胺-]乙基哌嗪。[125I]p-MPPI 对 5-HT1A 受体表现出高亲和力和选择性：Kd= 0.36 nM 和 Bmax= 264 大鼠海马膜匀浆中的蛋白质含量为 fmol/mg。该结合对 GTP (300 μM) 或 Gpp(NH)p (100 μM) 不敏感。在使用大鼠海马进行毛喉素刺激的腺苷酸环化酶测定中，与 (±)-8-OH-DPAT 相比，p-MPPI（高达 10 μM）没有表现出激动剂活性。在 100 nM 完全拮抗 100 nM (±)-8-OH-DPAT 产生的毛喉素刺激的腺苷酸环化酶活性的抑制作用。这种潜在的 5-HT1A 拮抗剂可能为研究 5-HT1A 受体系统的药理学提供强大的工具。
A potential 5-HT1Areceptor antagonist, p-MPPI, 4-(2'-methoxy-)phenyl-1-[2'-(n-2“-pyridinyl)-p-iodobenzamido-] ethyl-piperazine, was developed. The [125I]p-MPPI demonstrated high affinity and selectivity toward 5-HT1Areceptors: Kd= 0.36 nM and Bmax= 264 fmol/mg of protein in rat hippocampal membrane homogenates. The binding is not sensitive to GTP (300μM) or Gpp(NH)p (100 μM). In forskolin-stimulated adenylyl cyclase assay using rat hippocampus, p-MPPI (up to 10 μM) showed no agonist activity as compared to that of (±)-8-OH-DPAT. At 100 nM it completely antagonized the inhibition of forskolin-stimulated adenylyl cyclase activity produced by 100 nM of (±)-8-OH-DPAT. This potential 5-HT1Aantagonist may provide a powerful tool for studies of the pharmacology of the 5-HT1Areceptor system.