Propranolol is a mechanism-based inhibitor of CYP2D and CYP2D6 in humanized CYP2D6-transgenic mice: Effects on activity and drug responses.

ABSTRACT:

Background and purpose

Genetics and drug interactions contribute to large interindividual variation in human CYP2D6 activity. Here, we have characterized propranolol inhibition of human and mouse CYP2D using transgenic (TG) mice, which express both mouse CYP2D and human CYP2D6, and wild-type (WT) mice. Our purpose was to develop a method for in vivo manipulation of CYP2D6 enzyme activity which could be used to investigate the role of CYP2D6 in drug-induced behaviours.

Experimental approach

Dextromethorphan metabolism to dextrorphan was used to measure CYP2D activity and to characterize propranolol inhibition in vitro and in vivo. Effects of propranolol pretreatment (24 hr) on serum levels of the CYP2D6 substrate haloperidol and haloperidol-induced catalepsy were also studied

SUBMITTER: Tolledo EC 

PROVIDER: S-EPMC7012948 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature