Fig. 10.

a and b. A time-dependent plasma AChE inhibition achieved by (−)-Phen in anesthetized rats following a single dose, in which cholinesterase inhibition was achieved by the combined action of (−)-Phen and its primary metabolites. (−)-Phen and active metabolites readily enter the brain (see Fig. 3), and thereby induce brain AChE inhibition and elevate acetylcholine levels [110]. By contrast, (−)-Physostigmine at a higher dose achieves lower plasma AChE inhibition, has less brain uptake than (−)-Phen, is short-lived in vivo, and is associated with greater adverses actions [72]. b: Time-dependent plasma AChE inhibition and predicted brain pharmacokinetics of (−)-Phen and primary metabolites in humans after single acute dosing