[125I]-2-(2,5-dimethoxy-4-iodophenyl)aminoethane ([125I]-2C-I) as a label for the 5-HT2 receptor in rat frontal cortex.

A radiolabeled compound, [125I]-2C-I, was used to label low-density 5-HT2 agonist binding sites in brain tissue. The nonhydrolyzable GTP analog GppNHp inhibited high-affinity binding, and serotonin along with several 5-HT2 agonists and antagonists showed high affinity for the site. At 37°C, the number of binding sites (Bmax) decreased compared to 24°C, while binding affinity (KD) remained unchanged. Structure-activity relationships for displacing [125I]-2C-I supported the receptor's role in hallucinogen action. The findings demonstrate [125I]-2C-I as a useful radioligand and provide further evidence linking the 5-HT2 receptor to hallucinogenic activity.

Study at a glance

Abstract

Recent studies of 5-HT2 receptor binding have involved the use of radiolabeled agonists. This report describes the use of [125I]-2-(2,5-dimethoxy-4-iodophenyl)aminoethane ([125I]-2C-I) as a label for low-density 5-HT2 agonist binding sites. A nonhydrolyzable analog of GTP, GppNHp, was found to inhibit the high affinity binding of [125I]-2C-I. 5-HT and several 5-HT2 agonists and antagonists displayed high affinity for this site. In addition, a significant decrease in the Bmax value, but not the KD for [125I]-2C-I was observed at 37 degrees C as compared to that observed at 24 degrees C. Several structure-activity relationships were investigated for displacement of [125I]-2C-I, and the results are consistent with the importance of this receptor in the mechanism of action of hallucinogens. This study demonstrates the utility of [125I]-2C-I as a novel radioligand and provides further data that the 5-HT2 receptor is significantly linked to hallucinogenic activity for several compounds.