Influence of sanguinarine on the GABA synthesizing enzyme glutamate decarboxylase in vitro.

The inhibitory activity of the quaternary benzophenanthridine alkaloid sanguinarine on rat brain glutamate decarboxylase (GAD; EC 4.1.1.15) was studied in vitro. A value of Ki 7.10(-4) mol.1(-1) for sanguinarine was found. The inhibition was irreversible and increased during the preincubation time of sanguinarine with the GAD preparation. The results suggest that reaction of the iminium bond in the benzophenanthridine molecule with thiol groups of the enzyme participates in GAD inhibition. As GAD catalyzes the rate-limiting step of GABA synthesis, its inhibition by sanguinarine may contribute to its physiological action in vivo.