Differences in the permeability of the blood-brain barrier to cholinolytic substances

Summary

The object of study was the physicochemical properties and the penetration through the BBB (hematoencephalic barrier) in albino mice of atropine, amysil, and lachesine which were injected intravenously and into the lateral ventricle of the brain. The degree of penetration of these substances through the brain barrier was determined by the size of the dose (ED₅₀) preventing arecoline tremor in mice.

Comparison of the degree of penetration of cholinolytics through the BBB with their physicochemical properties showed that the molecular weight, percentage of ionization, and solubility of cholinolytics in water did not have a substantial effect on their penetration through the BBB. The PK_a and distribution coefficient were of certain significance for atropine, amysil, and lachesine penetration. As regards penetration through the BBB a difference was established not only between the tertiary and quaternary cholinolytics but also between tertiary compounds (amysil showed better penetration into the brain than atropine).