DISPLACEMENT ACTIVITY OF BISBENZYLISOQUINOLINE ALKALOIDS AT STRIATAL H-3 SCH 23390 AND H-3 RACLOPRIDE BINDING-SITES

Fifteen bisbenzylisoquinoline alkaloids (BBIQ) with one ether bridge (thaligrisine [1), berbamunine [2], dimethylgrisabine [3], pampulhamine [4], and methyldauricine [5]), with two ether bridges (homoaromoline, isotetrandrine, and obaberine), with one ether bridge and one biphenyl bridge (oxandrine, dimethylpseudoxandrine, pseudoxandrine, and antioquine) or secoderivatives (secoobaberine, secoantioquine, and secolucidine), were tested for their ability to displace H-3-raclopride or H-3-SCH 23390 from their specific dopaminergic binding sites to rat striatal membranes. The most active compounds were found in the group of BBIQs with one ether bridge. Inactive or weakly active compounds were found in this group of BBIQs with one ether bridge and in the other groups. Analysis of tridimensional representations indicates that the different activities among the BBIQs with one ether bridge could be related to strong differences between the spatial occupancy of these compounds according to their stereochemistry.