Stimulation of the pathway of porphyrin synthesis in the liver of rats and mice by griseofulvin, 3,5-Diethoxycarbonyl-1,4-dihydrocollidine and related drugs: evidence for two basically different mechanisms.

Griseofulvin and isogriseofulvin cause, like 3,5-diethoxycarbonyl-1,4-dihydrocollidine, a fall in the activity of the hepatic enzyme porphyrin-metal chelatase and accumulation of protoporphyrin in the liver. Analogues of either griseofulvin or 3,5-diethoxycarbonyl-1,4-dihydrocollidine which do not decrease the chelatase activity are not porphyrogenic on their own, but can potentiate the porphyria caused by 3,5-diethoxycarbonyl-1,4-dihydrocollidine. This suggests the existence of two basically different mechanisms by which drugs stimulate the pathway of porphyrin synthesis in the liver.