SYNTHESIS AND IN-VIVO EVALUATION OF [C-11] SEMOTIADIL, A BENZOTHIAZINE CALCIUM-ANTAGONIST

A carbon-11 labeled benzothiazine calcium antagonist, (+)-(R)-2-[5-methoxy-2-]3-[methyl[2-](3,4-methylenedioxy)phenoxylethyl]amino]propoxy]phenyl]-4-methyl-2H-1,4-benzothiazin-3(4H)-one (semotiadil), and its enantiomer were prepared by N-methylation of the corresponding norderivatives with (CH3I)-C-11: decay-corrected radiochemical yields of 16 - 27% based on (CH3I)-C-11, radiochemical, chemical and optical purity of >99%, sp. act. of 11 - 50GBq/mumol and preparation time of 35 - 40 min. In mice, saturable and stereo-selective uptake in the hippocampus, striatum and hypothalamus was observed. The potential of the compound to visualize the regional brain calcium channels in vivo by positron emission tomography was indicated; however, no promising sign was found in the myocardium.