A potential 5-HT1A receptor antagonist: p-MPPI.
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.
Kung
H F
HF
Department of Radiology, University of Pennsylvania, Philadelphia 19104.
Kung
M P
MP
Clarke
W
W
Maayani
S
S
Zhuang
Z P
ZP
D000262:Adenylyl Cyclases / Q000187:drug effects / Q000378:metabolism; D000631:Aminopyridines / Q000378:metabolism* / Q000494:pharmacology*; D000818:Animals; D001667:Binding, Competitive; D005576:Colforsin / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D007700:Kinetics; D008024:Ligands; D010879:Piperazines / Q000378:metabolism* / Q000494:pharmacology*; D051381:Rats; D011985:Receptors, Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013268:Stimulation, Chemical
D000631:Aminopyridines; D007457:Iodine Radioisotopes; D008024:Ligands; D010879:Piperazines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C087205:4-(2'-methoxyphenyl)-1-(2'-(N-(2''-pyridinyl)-4-iodobenzamido)ethyl)piperazine; D005576:Colforsin; D006160:Guanosine Triphosphate; D000262:Adenylyl Cyclases