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.

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.