A potential imaging agent for the GABAA receptor: 4-t-butyl-1-(4-[123I]iodophenyl)-2,6,7-trioxabicyclo-[2.2.2]octane.
Based upon the known high toxicity and high antagonist activity of t-butylorthobenzoates towards the GABA receptor complex, 4-t-butyl-1-(4-iodophenyl)-2,6,7-trioxabicyclo[2.2.2]octane 5 and its radioiodo analogues ([123I]-5 and [131I]-5 were prepared as potential markers for the gated chloride channel of GABAA receptors. Mice showed rapid clearance of [131I]-5 from all organs including the brain. The radioactivity was found to proceed into the urine in spite of the high lipophilicity of 5, the high binding affinity of 5 for plasma protein and the apparent chemical stability of 5 in plasma.
Department of Chemistry, University of Western Ontario, London, Canada.
P A
PA
Culbert
S
S
Chan
A V
AV
Wearring
M J
MJ
Chamberlain
D H
DH
Hunter
D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis / Q000378:metabolism* / Q000493:pharmacokinetics; D019086:Bridged Bicyclo Compounds, Heterocyclic; D018118:Chloride Channels; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes; D007462:Iodobenzenes / Q000138:chemical synthesis / Q000378:metabolism* / Q000493:pharmacokinetics; D007553:Isotope Labeling / Q000379:methods; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D011963:Receptors, GABA-A / Q000032:analysis*; D014018:Tissue Distribution
D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D018118:Chloride Channels; D007457:Iodine Radioisotopes; D007462:Iodobenzenes; D008565:Membrane Proteins; D011963:Receptors, GABA-A; C081500:4-tert-butyl-1-(4-iodophenyl)-2,6,7-trioxabicyclo(2.2.2)octane; C046308:tert-butylbicyclo-2-benzoate