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

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 greater than 2'-ISP greater than HP greater than 4-ISP greater than 2'-IHP greater than 2'-ITP. Whereas, the serotonin (S-2) receptor binding affinity of SP and its iodinated analogues were in the order of SP much greater than 4-ISP greater than 2'-ISP. Furthermore, in the saturation binding study using the striatal membrane preparations, the 2'-ISP displayed a KD of 0.25 nM with maximum number of binding site Bmax 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.