title: Inhibition of brain choline uptake by isoarecolone and lobeline derivatives: implications for potential vector-mediated brain drug delivery.
abstract: Delivery of certain compounds to brain is restricted by the nature of the blood-brain barrier (BBB). Many valuable pharmaceuticals are excluded from the CNS due to hydrophilicity or charge. These limitations have been overcome by numerous methods. One method we use is to take advantage of saturable nutrient transporters located at the barrier. These systems transport hydrophilic and charged nutrients into brain such as choline, a quaternized neurotransmitter precursor. Using knowledge of their substrate specificity, it is possible to deliver agents into brain using these nutrient carriers. In this report, derivatives of lobeline and isoarecolone were evaluated to determine if they may gain access to brain by the blood-brain barrier basic amine transporter using the in situ brain perfusion technique. These compounds do bind the blood-brain barrier basic amine transporter and may enter brain by this transport system.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo 79106-1712, USA.
authors.forename: T L
authors.initials: TL
authors.lastname: Metting
authors.forename: D E
authors.initials: DE
authors.lastname: Burgio
authors.forename: A V
authors.initials: AV
authors.lastname: Terry
authors.forename: J W
authors.initials: JW
authors.lastname: Beach
authors.forename: C R
authors.initials: CR
authors.lastname: McCurdy
authors.forename: D D
authors.initials: DD
authors.lastname: Allen
mesh_terms: D000818:Animals; D001115:Arecoline / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D001692:Biological Transport / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002794:Choline / Q000378:metabolism*; D016503:Drug Delivery Systems; D066298:In Vitro Techniques; D008120:Lobeline / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D008297:Male; D018722:Nicotinic Agonists / Q000493:pharmacokinetics*; D010477:Perfusion; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D018722:Nicotinic Agonists; C095493:isoarecolone; D001115:Arecoline; D008120:Lobeline; D002794:Choline