Predicting the brain-penetrating capability of histaminergic compounds.

Recently published data on histaminergic H1-receptor agonists are used to evaluate two models for predicting brain penetration. The physicochemical model of Young et al., using the parameter delta log P (the difference between the measured partition coefficients log octanol/water and log cyclohexane/water) is found to overestimate the brain penetration of the agonists by factors of 2-5. A theoretical model of van de Waterbeemd and Kansy, using the calculated parameters VM (molar volume) and SP (polar surface area) is found to overestimate the brain penetration by even larger factors.