BRAIN PENETRATION OF THE HISTAMINE H-3 RECEPTOR ANTAGONISTS THIOPERAMIDE AND CLOBENPROPIT IN RAT AND MOUSE, DETERMINED WITH EX-VIVO [I-125]IODOPHENPROPIT BINDING

We investigated the brain penetration of the histamine H-3 receptor an tagonists thioperamide and clobenpropit using ex vivo [I-125]iodophenp ropit binding. Homogenates of the rat cortex, striatum and mouse whole brain were prepared 1 h after subcutaneous injection of the H-3 antag onists and incubated with [I-125]iodophenpropit, a radiolabeled H-3 re ceptor antagonist, to determine the H-3 receptor occupancy. Specific [ I-125]iodophenpropit binding to the rat cortex and striatum was inhibi ted by thioperamide with IC30 values of 1.0 and 1.5 mg/kg, respectivel y. Clobenpropit also inhibited [I-125]iodophenpropit binding, but was less potent (IC30: 18 and 19 mg/kg in the rat cortex and striatum, res pectively) than thioperamide. Similar results were obtained in experim ents with mouse whole brain (3.5 and 13 mg/kg for thioperamide and clo benpropit), indicating that there is no important species differences in the brain penetration of these drugs between rats and mice. These f indings suggest that after peripheral injection both in rat and mouse thioperamide penetrates the blood-brain barrier more efficiently compa red to clobenpropit.