In vivo binding of [123I]4-(2′-methoxy phenyl)-1-[2′-(N-2″-pyridinyl)-P-iodobenzamido-]ethyl-piperazine, p-MPPI, to 5-HT1A receptors in rat brain
✍ Scribed by Mei-Ping Kung; Zhi-Ping Zhuang; Dana Frederick; Hank F. Kung
- Publisher
- John Wiley and Sons
- Year
- 1994
- Tongue
- English
- Weight
- 862 KB
- Volume
- 18
- Category
- Article
- ISSN
- 0887-4476
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✦ Synopsis
The in vivo regional distribution and pharmacological profile of a novel iodinated phenylpiperazine derivative, [12311p-MPPI (4-(2'-methoxy-)phenyl-l-[2'-(N-2"pyridinyl)-p-iodobenzamido-Iethyl-piperazine), in the rat brain were evaluated for use as a potential in vivo imaging agent for 5-HTlA 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 hippocampuskerebellum was 3.3 at 30 min postinjection. The specific binding of the radioligand in the hippocampal region, an area rich in 5-HTlA receptor density, was blocked by pretreatment with a dose of (k) 8-OH-DPAT (2 mgkg, i.v.1 or WAY 100635 (1 mgkg, i.v.), whereas the regional distribution of [1231]p-MPPI was unaffected by pretreatment with non-5-HTlA agents such as ketanserin or haloperidol.
Ex vivo autoradiographic studies further confirmed that the specific binding of [12511p-MPPI is associated with 5-HTlA receptor sites. These results indicate that [12311p-MPPI may be a useful candidate for noninvasive single photon emission computed tomography (SPECT) imaging of 5-HTlA receptor sites in the living human brain.