Transporter-mediated Efflux Influences CNS Side Effects: ABCB1, from Antitarget to Target.

ABSTRACT: We examined the relationship between sedation and orthostatic hypotension, two central side effects and ABCB1 transporter-mediated efflux for a set of 64 launched drugs that are documented as histamine H1 receptor antagonists. This relationship was placed in the context of passive diffusion (estimated using LogP, the octanol/water partition coefficient), receptor affinity, and the adjusted therapeutic daily dose, in order to account for side effect variability. Within this set, CNS permeability was not dependent on passive diffusion, as no significant differences were found for LogP and its pH-corrected equivalent, LogD(74). Sedation and orthostatic hypotension can be explained within the framework of ABCB1-mediated efflux and adjusted dose, while target potency has less influence. ABCB1,

SUBMITTER: Broccatelli F 

PROVIDER: S-EPMC3281213 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature