SYNTHESIS AND PRELIMINARY EVALUATION OF HYDROQUINONE-SUBSTITUTED HISTIDINE DERIVATIVES AS PUTATIVE HISTAMINERGIC NEUROTOXINS

A series of hydroquinone-substituted histidine derivatives were synthe sized as potential histaminergic neurotoxins. The compounds undergo au toxidation at physiologic pH as exemplified by -3-[2-4,5,-trihydroxyph enyl)imidazo-4-yl]propionic acid 11. One of the synthesized histidine derivatives, namely o-3-[2-(2,3-dihydroxyphenyl)imidazo-4-yl]propionic acid 8, was tested for its degenerating effect on histaminergic, dopa minergic and serotonergic neurons in rat brain. After 4 d of an unilat eral injection of 1 mu l 3 mM 8 in 0.1 M phosphate buffer (pH 7.4) int o the posterior hypothalamus, a decrease in immunoreactivity in the pr esumable histaminergic neurons was observed whilst dopaminergic and se rotonergic neuronal elements were little affected. A possible mechanis m of action is discussed.