Effect of age on functional P-glycoprotein in the blood-brain barrier measured by use of (R)-[11C]verapamil and positron emission tomography

Abstract

This study showed decreased P-gp activity during aging. Consequently, the brain may be exposed to higher drug and toxin levels in elderly subjects.

Image-derived input functions for PET brain studies

“…11 C] verapamil is a tracer for measuring P-glycoprotein function in vivo, which may play an important role in several neurological disorders such as Alzheimer's disease [9] and normal ageing [10]. Finally, (R)-[ 11 C]PK11195 is a marker of activated microglia, which is used to measure inflammation in neurological disorders [11].…”

Quantification of 11C-Laniquidar Kinetics in the Brain

“…Several P-glycoprotein tracers have been proposed, but in practice only (R)-11 C-verapamil and 11 C-N-desmethylloperamide have been used to assess P-glycoprotein function (3)(4)(5)(6)(7). Because both ligands are substrates of P-glycoprotein, their concentration in the brain is low.…”

Cluster headache and intracranial aneurysm

“…In addition, the blood-brain barrier is a major impediment to the entry of many therapeutic drugs into the brain. PGlycoprotein is an ATP-dependent drug transport protein that is predominantly found in the luminal membrane of the brain capillary endothelial cells that make up the blood-brain barrier [32]. As P-glycoprotein can actively transport a vast variety of hydrophobic amphipathic substances out of the cell, it was hypothesised that it might be responsible for the very poor penetration of many relatively large (>400 Da) hydrophobic drugs in the nervous parenchyma, by performing active back-transport of these substances to the blood.…”

“…As P-glycoprotein can actively transport a vast variety of hydrophobic amphipathic substances out of the cell, it was hypothesised that it might be responsible for the very poor penetration of many relatively large (>400 Da) hydrophobic drugs in the nervous parenchyma, by performing active back-transport of these substances to the blood. As verapamil may affect the P-glycoprotein, it can be hypothesised that, at least in part, the pain relief induced by it is likely to be somehow linked to the blood-brain barrier permeability [32,33]. Anticonvulsant activity of verapamil has also been described [33].…”