title: In vivo binding of [123I]4-(2'-methoxyphenyl)-1-[2'-(N-2"-pyridinyl)- p-iodobenzamido-]ethyl-piperazine, p-MPPI, to 5-HT1A receptors in rat brain.
abstract: The in vivo regional distribution and pharmacological profile of a novel iodinated phenylpiperazine derivative, [123I]p-MPPI (4-(2'-methoxy-)phenyl-1-[2'-(N-2"pyridinyl)-p-iodobenzamido-]ethy l- piperazine), in the rat brain were evaluated for use as a potential in vivo imaging agent for 5-HT1A receptors. The new ligand penetrated the blood-brain barrier quickly and efficiently, with 1.2% of the injected dose found in the whole brain at 2 min post i.v. injection. The rate of radioactivity washout was slowest from the hippocampal region, followed by the hypothalamus, cortex, striatum, and cerebellum. The maximum ratio of hippocampus/cerebellum was 3.3 at 30 min postinjection. The specific binding of the radioligand in the hippocampal region, an area rich in 5-HT1A receptor density, was blocked by pretreatment with a dose of (+/-) 8-OH-DPAT (2 mg/kg, i.v.) or WAY 100635 (1 mg/kg, i.v.), whereas the regional distribution of [123I]p-MPPI was unaffected by pretreatment with non-5-HT1A agents such as ketanserin or haloperidol. Ex vivo autoradiographic studies further confirmed that the specific binding of [125I]p-MPPI is associated with 5-HT1A receptor sites. These results indicate that [123I]p-MPPI may be a useful candidate for noninvasive single photon emission computed tomography (SPECT) imaging of 5-HT1A receptor sites in the living human brain.
authors.affiliation: Department of Radiology, University of Pennsylvania, Philadelphia 19104.
authors.forename: M P
authors.initials: MP
authors.lastname: Kung
authors.forename: Z P
authors.initials: ZP
authors.lastname: Zhuang
authors.forename: D
authors.initials: D
authors.lastname: Frederick
authors.forename: H F
authors.initials: HF
authors.lastname: Kung
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000631:Aminopyridines / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D007457:Iodine Radioisotopes; D007553:Isotope Labeling; D008024:Ligands; D008297:Male; D010879:Piperazines / Q000138:chemical synthesis / Q000493:pharmacokinetics* / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000138:chemical synthesis / Q000493:pharmacokinetics* / Q000494:pharmacology; D014018:Tissue Distribution
chemical_list: D000631:Aminopyridines; D007457:Iodine Radioisotopes; D008024:Ligands; D010879:Piperazines; D011725:Pyridines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C087205:4-(2'-methoxyphenyl)-1-(2'-(N-(2''-pyridinyl)-4-iodobenzamido)ethyl)piperazine; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin