In order to study the role of nitric oxide in a number of pathological states, this work focuses on the discovery and development of inhibitors of nitric oxide synthase that can be used for in vivo imaging by positron emission tomography. During the past year we have developed a series of compounds containing a dithiocarbamate moiety and a tertiary amino group, separated by five carbons. These compounds show modest activity in their ability to displace [3H]-L-N(G)-nitroarginine from rat brain membranes and moderate inhibition of the conversion of [3H]-L- arginine to [3H]-citrulline with isolated enzyme. One compound, S-methyl N-(1-ethylpyrrolidin-2-yl)methyl dithiocarbamate, has been labeled (at the S-methyl position) with Carbon-11. Preliminary ex vivo studies show rapid uptake (< 5 min) into rat brains with washout nearly complete in 60 minutes. No labeled metabolites are detectable.
