DAA1106 is an agonist of the 18 kDa translocator protein TSPO, which was previously known as the peripheral benzodiazepine receptor (PBR), that has an IC50 value of 0.28 nM in a radioligand binding assay.1 It is selective for TSPO over central benzodiazepine receptors (CBRs) and GABAA receptors in rat whole brain membranes, as well as a panel of 54 ion channels, uptake/transporters, and secondary messenger receptors at concentrations greater than 10 ?M. DAA1106 increases mitochondrial prognenolone formation in rat brain homogenates, which indirectly potentiates GABAA receptor signaling. DAA1106 (1-10 mg/kg) increases the time mice spend in the light area of the light/dark exploration and the time rats spend in open arms of the elevated plus maze in a dose-dependent manner, suggesting a decrease in anxiety-like behavior. Various radiolabeled versions of DAA1106 have been synthesized to study the distribution of PBRs in neurological disease models using positron emission tomography (PET).2,3
1.Okuyama, S., Chaki, S., Yoshikawa, R., et al.Neuropharmacological profile of peripheral benzodiazepine receptor agonists, DAA1097 and DAA1106Life Sci.64(16)1455-1464(1999) 2.Zhang, M.-R., Kida, T., Noguchi, J., et al.[11C]DAA1106: radiosynthesis and in vivo binding to peripheral benzodiazepine receptors in mouse brainNucl. Med. Biol.30(5)513-519(2003) 3.Venneti, S., Wagner, A.K., Wang, G., et al.The high affinity peripheral benzodiazepine receptor ligand DAA1106 binds specifically to microglia in a rat model of traumatic brain injury: Implications for PET imagingExp. Neurol.207(1)118-127(2007)