Statins and neuroprotection: basic pharmacology needed.
Statins are attracting great interest albeit with some controversy in treating certain neurodegenerative diseases such as Alzheimer disease, Parkinson disease, multiple sclerosis, ischemic stroke, and traumatic brain injury. Support for the use of statins has come from human studies and animal and cell models. Despite the intense level of interest, there is a deficiency in information on the basic pharmacokinetics and pharmacodynamics of statins in the brain. The purpose of this focused review is to examine what is known and the gaps in our knowledge on detectability of statin lactones and acids in the brain, membrane partitioning and active transport of statins across the blood-brain barrier, and statin effects on brain isoprenoid levels. Statins may be efficacious in treating certain neurodegenerative diseases. Having basic information on statin pharmacokinetics and pharmacodynamics in the brain would provide insight into specific drug targets and also provide the rationale for optimizing statins in terms of enhancing brain influx and inhibiting efflux.
Geriatric Research, Education and Clinical Center, VAMC, Department of Pharmacology, University of Minnesota School of Medicine, Jackson Hall 6-120, 321 Church St, Minneapolis, MN, 55455, USA, woodx002@umn.edu.
W Gibson
WG
Wood
Walter E
WE
Mΰller
Gunter P
GP
Eckert
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018696:Neuroprotective Agents