title: Radiochemical synthesis and biodistribution of a novel maxi-K potassium channel opener.
abstract: The racemate 1, ((+/-)-(5-Chloro-2-methoxyphenyl)-1,3-dihydro-3-fluoro-6-(trifluoromethyl)- 2H-indol-2-one), is a potent, specific and novel opener of cloned large-conductance, calcium-activated (maxi-K) potassium channels. One of its enantiomers, BMS-204352 (MaxiPost), is undergoing clinical evaluation for efficacy in patients with suspected acute stroke. In the current study, we have prepared [(18)F]-labeled 1 using a silver assisted nucleophilic substitution to examine its distribution and disposition in the rat, with particular emphasis on the brain. Biodistribution studies in rats confirm that brain uptake is rapid and occurs at high levels, and indicate that a major fraction of the compound in the brain does not accumulate by a specific, saturable mechanism.
authors.affiliation: Positron Emission Tomography Department, Clinical Center, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892-1180, USA. dk7k@nih.gov
authors.forename: Dale O
authors.initials: DO
authors.lastname: Kiesewetter
authors.forename: Elaine M
authors.initials: EM
authors.lastname: Jagoda
authors.forename: John E
authors.initials: JE
authors.lastname: Starrett
authors.forename: Valentin K
authors.initials: VK
authors.lastname: Gribkoff
authors.forename: Piyasena
authors.initials: P
authors.lastname: Hewawasam
authors.forename: Nugahally
authors.initials: N
authors.lastname: Srinivas
authors.forename: Daniel
authors.initials: D
authors.lastname: Salazar
authors.forename: William C
authors.initials: WC
authors.lastname: Eckelman
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D007211:Indoles / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D018696:Neuroprotective Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D015221:Potassium Channels / Q000187:drug effects; D051381:Rats; D014018:Tissue Distribution
chemical_list: C424388:BMS204352; D007211:Indoles; D018696:Neuroprotective Agents; D015221:Potassium Channels