In vitro evaluation of radioiodinated butyrophenones as radiotracer for dopamine receptor study

Abstract

Radioiodinated butyrophenone compounds are attracting the interest of those working on dopamine receptor studies; structure-activity relationship study has revealed the ortho position of the p-fluorobutyrophenone moiety as a very plausible iodination site. Various synthesized butyrophenones iodinated at the ortho position of p-fluorobutyrophenone moiety, 2′- iodohaloperidol (2′-IHP), 2′-iodotrifluperidol (2′-ITP) and 2′-iodospiperone (2′-ISP) were tested for their abilities to inhibit 3H-spiperone (SP) binding for the dopamine (D-2) receptor, together with reference compounds (SP, haloperidol (HP) and 4-iodospiperone (4- ISP)). The order of binding affinity of the tested compounds was SP > 2′-ISP > HP > 4-ISP > 2′-IHP > 2′- ITP. Whereas, the serotonin (S-2) receptor binding affinity of SP and its iodinated analogues were in the order of SP > > 4-ISP > 2′-ISP. Furthermore, in the saturation binding study using the striatal membrane preparations, the 2′-ISP displayed a K D of 0.25 nM with maximum number of binding site B max of 210 fmol/mg protein. These data indicated the 2′-ISP as holding high affinity for dopamine receptors and a low affinity for serotonin receptors. Thus, the 125I-2′-ISP was a very potent radioligand for in vitro dopamine (D-2) receptor studies, and 123I-2′-ISP holds very promising characteristics as for in vivo dopamine receptor studies, as well.