Synthesis, radiolabeling and bioevaluation of a novel arylpiperazine derivative containing triazole as a 5-HT1A receptor imaging agents.

BACKGROUND

It has been recognized that serotonin plays a main role in various pathological conditions such as anxiety, depression, aggressiveness, schizophrenia, suicidal behavior, panic and autism. 1-(2-Methoxyphenyl) piperazine pharmacophore, a fragment of the true 5-HT(1A) antagonist WAY100635, is found in numerous selective 5-HT(1A) imaging agents. In this paper, we have reported the synthesis of a novel derivative of 1-(2-methoxyphenyl) piperazine that is labeled with (99m)Tc (CO)(3) via click chemistry.

METHODS

The bidentate alkyne, propargylglycine was reacted with phenyl piperazine triazole derivative in the presence of a catalytic amount of Cu (I) to form tridentate ligand. The ligand was radiolabeled with the precursor [(99m)Tc] [(H(2)O)(3) (CO)(3)](+) and characterized by HPLC. The bioevaluation of radio labeled ligand was carried out in rats.

RESULTS

Triazole complex was labeled by (99m)Tc-tricarbonyl and its radiochemical yield was more than >95% which was determined by HPLC. In vivo stability studies in human serum albumin show a 93% ratio of complex after a 24h period. The calculated partition coefficient (logP) was 0.34±0.02. Receptor binding assays indicated about 70% specific binding of radioligand to 5-HT(1A) receptors. Biodistribution studies have shown brain hippocampus uptake of 0.40±0.08 %ID/g at 30 min post injection.

CONCLUSIONS

Results indicate that this (99m)Tc-tricabonyl-arylpiperazine derivative has specific binding to 5-HT(1A) receptors and presented suitable characters for its use as a CNS imaging agent.