In vivo binding of [ 123 I]4‐(2′‐methoxy phenyl)‐1‐[2′‐(N‐2″‐pyridinyl)‐P‐iodobenzamido‐]ethyl‐piperazine, p‐MPPI, to 5‐HT 1A receptors in rat brain

The in vivo regional distribution and pharmacological profile of a novel iodinated phenylpiperazine derivative, [ 123 I]p‐MPPI (4‐(2′‐methoxy‐)phenyl‐l‐[2′‐(N‐2″pyridinyl)‐p‐iodobenzamido‐]ethyl‐piperazine), in the rat brain were evaluated for use as a potential in vivo imaging agent for 5‐HT 1A 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‐HT 1A 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 [ 123 I]p‐MPPI was unaffected by pretreatment with non‐5‐HT 1A agents such as ketanserin or haloperidol. Ex vivo autoradiographic studies further confirmed that the specific binding of [ 123 I]p‐ MPPI is associated with 5‐HT 1A receptor sites. These results indicate that [ 123 I]p‐MPPI may be a useful candidate for noninvasive single photon emission computed tomography (SPECT) imaging of 5‐HT 1A receptor sites in the living human brain. © 1994 Wiley‐Liss, Inc.