Abstract
A potential 5-HT1A receptor antagonist, p-MPPI, 4-(2'-methoxy-)phenyl-1-[2'-(n-2"-pyridinyl)-p-iodobenzamido-]ethy l- 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 (300 microM) or Gpp(NH)p (100 microM). In forskolin-stimulated adenylyl cyclase assay using rat hippocampus, p-MPPI (up to 10 microM) 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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adenylyl Cyclases / drug effects
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Adenylyl Cyclases / metabolism
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Aminopyridines / metabolism*
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Aminopyridines / pharmacology*
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Animals
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Binding, Competitive
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Colforsin / pharmacology
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Guanosine Triphosphate / pharmacology
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Hippocampus / drug effects
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Hippocampus / metabolism
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Hippocampus / ultrastructure
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In Vitro Techniques
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Iodine Radioisotopes
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Kinetics
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Ligands
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Piperazines / metabolism*
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Piperazines / pharmacology*
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Rats
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Receptors, Serotonin / metabolism*
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Serotonin Antagonists / pharmacology*
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Stimulation, Chemical
Substances
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Aminopyridines
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Iodine Radioisotopes
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Ligands
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Piperazines
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Receptors, Serotonin
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Serotonin Antagonists
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4-(2'-methoxyphenyl)-1-(2'-(N-(2''-pyridinyl)-4-iodobenzamido)ethyl)piperazine
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Colforsin
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Guanosine Triphosphate
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Adenylyl Cyclases