Pesticide Science (1992) 36: 135-142.

Béla Darvas, Huw H. Rees, Nigel Hoggard, Mahmoud H. Tag El-Din, Eiichi Kuwano, Iván Bélai & Tibor Timár

Cytochrome P-450 inducers and inhibitors

The cytochrome P-450-dependent microsomal and mitochondrial ecdysone 20-monooxygenase systems convert ecdysone into 20-hydroxyecdysone. The microsomal fraction of fat bodies of zero h wandering stage fleshfly larvae (Neobellieria bullata; Diptera: Sarcophagidae) has a high ecdysone 20-monooxygenase activity. The effects of cytochrome P-450 inhibitors were investigated in vitro on microsomal ecdysone 20-monooxygenase. Metyrapone, fenarimol and certain imidazole derivatives (KK-42, KK-110, KK-135 and PIM) are strong inhibitors. The IC50 value of KK-110, which is the strongest inhibitor, is 2 x 10-7 M. A triazolyl and two cyclopropylamine derivatives have low activity. The activities of different NADPH-cytochrome c (P-450) reductase inhibitors were also assessed; diquat dibromide is a moderate inhibitor of microsomal ecdysone 20-monooxygenase, while paraquat dichloride has no activity.
In vivo experiments with cytochrome P-450 inducers and inhibitors gave the following results: (a) fenarimol, FI-121, precocene-2 caused ’permanent’ firstinstar larvae; (b) barbital, phenobarbital and their sodium salts caused significant delay in larval development; (c) PIM, PTM, metyrapone, KK-42, KK-135, J-2710. RH 5849 and colchicine caused moulting disturbances; (d) J-2710, PIM, PTM, KK-42, KK-135, RH 5849 and colchicine caused lethal spiracle and mandible malformation; (e) KK-110, fenarimol, barbital and phenobarbital caused precocious pupariation.