title: Permeability of the Blood-Brain Barrier: Molecular Mechanism of Transport of Drugs and Physiologically Important Compounds.
abstract: A new molecular model for the permeability of drugs and other physiologically important compounds to cross the blood-brain barrier has been developed. Permeability (log PS) is dependant on desolvation, lipophilicity, molecular volume and dipole moment. Previous models for BBB permeability have not considered desolvation and dipole moment as critical factors. The model applies to passive diffusion processes, and some facilitated diffusion processes. Passive permeability models may not apply to active transport processes, where complex membrane protein binding processes (e.g. stereoselectivity) are involved. Model phosphatidylcholine lipid bilayer membranes have been used to evaluate how charged or polar neutral compounds can interact through their molecular dipoles with the cell membrane to induce electromechanical changes in the cell membrane which facilitate permeation. The free energy of solvation in n-octanol has been shown to be a good measure of membrane lipophilicity by calculating the solvation free energy of a model PC lipid membrane in a series of closely related alcohols. The passive diffusion model for alcohols correlates with the known modulation of membrane bilayers which showed a size-dependent "cut-off" point in potency. For most drugs and related molecules, the neutral species are the permeating species.
authors: Eigenenergy, Adelaide, SA, Australia, cwfong@internode.on.net.
authors: Clifford W
authors: CW
authors: Fong
mesh_terms: D000818:Animals; D001693:Biological Transport, Active / Q000502:physiology; D001812:Blood-Brain Barrier / Q000737:chemistry / Q000378:metabolism; D002463:Cell Membrane Permeability; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D008954:Models, Biological; D008956:Models, Chemical; D010539:Permeability; D010713:Phosphatidylcholines / Q000737:chemistry / Q000378:metabolism
chemical_list: D008051:Lipid Bilayers; D010713:Phosphatidylcholines