title: Synthesis and in vivo evaluation of [11C]zolpidem, an imidazopyridine with agonist properties at central benzodiazepine receptors.
abstract: The synthesis and evaluation of [(11)C]zolpidem, an imidazopyridine with agonist properties at central benzodiazepine receptors, is reported herein. The reaction of desmethylzolpidem with [(11)C] methyl iodide afforded the title compound [(11)C]zolpidem in a yield of 19.19 +/- 3.23% in 41 +/- 2 min in specific activities of 0.995-1.19 Ci/micromol (1.115 +/- 0.105 Ci/micromol) (n = 3; decay corrected, EOB). The amount of radioactivity in the brain after tail vein injection in male Wistar rats was low, and the regional distribution was homogeneous and not consistent with the known distribution of the central benzodiazepine receptors. The frontal cortex/cerebellum ratio was not significantly greater than one (1.007 +/- 0.266 at 5 min) and did not increase from 5 to 40 min post-injection. A PET brain imaging study in one baboon confirmed the results obtained in rats. Therefore, it can be concluded that [(11)C]zolpidem is not a suitable tracer for in vivo visualization of central benzodiazepine receptors.
authors.affiliation: Department of Psychiatry, Columbia University, 1051 Riverside Drive, New York, New York 10032, USA.
authors.forename: Filip
authors.initials: F
authors.lastname: Dumont
authors.forename: Rikki N
authors.initials: RN
authors.lastname: Waterhouse
authors.forename: Julie A
authors.initials: JA
authors.lastname: Montoya
authors.forename: Filomena
authors.initials: F
authors.lastname: Mattner
authors.forename: Andrew
authors.initials: A
authors.lastname: Katsifis
authors.forename: Lawrence S
authors.initials: LS
authors.lastname: Kegeles
authors.forename: Marc
authors.initials: M
authors.lastname: Laruelle
mesh_terms: D000818:Animals; D018755:GABA Agonists / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D010215:Papio; D011725:Pyridines / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects*; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed; D000077334:Zolpidem
chemical_list: D018755:GABA Agonists; D011725:Pyridines; D011963:Receptors, GABA-A; D000077334:Zolpidem