DAA-1106

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 GABA_A 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 GABA_A 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)