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, [I-123]p-MPPI (4-(2'-methoxy-)phenyl-1-[2'-(Na-2 '' pyridinyl)-p-iodobenzamido-]ethyl-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 [I-123]p-MPPI was unaffected by pretreatment with non-5-HT1A agents such as ketanserin or haloperidol. Ex vive autoradiographic studies further confirmed that the specific binding of [I-125]p-MPPI is associated with 5-HT1A receptor sites. These results indicate that [I-123]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. (C) 1994 WiIey-Liss, Inc.