Autoradiographic localization of 5HT 2 receptors in rat brain using [ 125I]-DOI, a selective psychotomimetic radioligand

Abstract

1. Binding sites for the R and S enantiomers of the 5HT 2 agonist DOI (2,5-dimethoxy-4-iodophenylisopropylamine) were identified in rat brain using quantitative in-vitro autoradiography and compared with [ 125I]-LSD binding. 2. In most regions of the brain, binding density of the less active isomer [ 125I]S-DOI was 15 to 85% of that exhibited by the active [ 125I]R-DOI isomer. 3. Cortical membrane preparations exhibited two binding sites, of the enantiomers with high (Kd H) and low (Kd L) affinity constants of 1.2 ± 0.02 nM and 29 ± 7 nM for the [125 I]R-DOI and 2.1 ± 0.2 nM and 18 ± 4 nM for [125 I]s-DOI respectively. The respective high (Bmax H) and low (Bmax L) binding densities were 92 ± 10 and 536 ± 164 fmol/mg protein for the [125 I]R-DOI and 67 ± 19 and 245 ± 60 fmol/mg protein for [125 I]s-DOI. 4. Our results correlate with regional distribution of 5HT 2 receptors reported in previous studies and indicate that DOI and its congeners have potential clinical applications for the in-vivo localization of 5HT 2 receptors.