A potential 5-HT1A receptor antagonist: p-MPPI

Hank F. Kung; Mei Ping Kung; William Clarke; Saul Maayani; Zhi Ping Zhuang

doi:10.1016/0024-3205(94)00686-5

A potential 5-HT_1A receptor antagonist: p-MPPI

Hank F. Kung, Mei Ping Kung, William Clarke, Saul Maayani, Zhi Ping Zhuang

Research output: Contribution to journal › Article › peer-review

62 Scopus citations

Abstract

A potential 5-HT_1A receptor 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-HT_1A receptors: K_d = 0.36 nM and B_max = 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-HT_1A antagonist may provide a powerful tool for studies of the pharmacology of the 5-HT_1A receptor system.

Original language	English (US)
Pages (from-to)	1459-1462
Number of pages	4
Journal	Life Sciences
Volume	55
Issue number	19
DOIs	https://doi.org/10.1016/0024-3205(94)00686-5
State	Published - 1994
Externally published	Yes

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)
Pharmacology, Toxicology and Pharmaceutics(all)

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title = "A potential 5-HT1A receptor antagonist: p-MPPI",

abstract = "A potential 5-HT1A receptor 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-HT1A receptors: 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-HT1A antagonist may provide a powerful tool for studies of the pharmacology of the 5-HT1A receptor system.",

author = "Kung, {Hank F.} and Kung, {Mei Ping} and William Clarke and Saul Maayani and Zhuang, {Zhi Ping}",

year = "1994",

doi = "10.1016/0024-3205(94)00686-5",

language = "English (US)",

volume = "55",

pages = "1459--1462",

journal = "Life Sciences",

issn = "0024-3205",

publisher = "Elsevier Inc.",

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T1 - A potential 5-HT1A receptor antagonist

T2 - p-MPPI

AU - Kung, Hank F.

AU - Kung, Mei Ping

AU - Clarke, William

AU - Maayani, Saul

AU - Zhuang, Zhi Ping

PY - 1994

Y1 - 1994

N2 - A potential 5-HT1A receptor 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-HT1A receptors: 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-HT1A antagonist may provide a powerful tool for studies of the pharmacology of the 5-HT1A receptor system.

AB - A potential 5-HT1A receptor 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-HT1A receptors: 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-HT1A antagonist may provide a powerful tool for studies of the pharmacology of the 5-HT1A receptor system.

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SP - 1459

EP - 1462

JO - Life Sciences

JF - Life Sciences

IS - 19

ER -

A potential 5-HT_1A receptor antagonist: p-MPPI

Abstract

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