INHIBITORS OF CYP6D1 IN-HOUSE FLY MICROSOMES

CYP6D1 is a cytochrome P450 responsible for the metabolism of insectic ides and other xenobiotics in the house fly (Musca domestica). Using a CYP6D1-specific monooxygenase activity and a non-CYP6D1-specific mono oxygenase activity, 21 compounds were evaluated as inhibitors of CYP6D 1 in house fly microsomes, CYP6D1 was strongly inhibited by xanthotoxi n, chlorpyrifos, beta-naphthoflavone, piperonyl butoxide and 5-methoxy psoralen. The highest selectivity for inhibition of CYP6D1 was seen fo r 5-methoxypsoralen, xanthotoxin, beta-naphthoflavone, chlorpyrifos ox on, isosafrole and psoralen, The results clearly indicate that identif ication of isoform-selective inhibitors of P450s within an insect, and across species, is possible, In addition, psoralen and 5-methoxypsora len stimulated ethoxycoumarin O-deethylation suggesting that these com pounds were substrates for monooxygenases in house fly microsomes, Iso safrole was shown to be a potent synergist of pyrethroid insecticides in adult house flies. Copyright (C) 1996 Published by Elsevier Science Ltd.