Biological Activity
bd 1008 dihydrobromide is a potent and selective ligand for σ-receptor with ki values of 2 and 8 nm for σ-1 receptor and σ-2 receptor, respectively [1].σ-receptor is a type of opioid receptor. there are two subtypes of σ-receptor: σ-1 and σ-2 [2].bd 1008 dihydrobromide is a potent and selective σ-receptor ligand. bd1008 showed high affinity to sites labeled by 4-[125i]pemp with ki value of 5.06 nm in guinea pig brain membranes. in mcf-7 breast cancer and melanoma (a375) cells, 4-[125i]pemp inhibited the binding of bd1008 with ki value of 11 nm in a dose-dependent way [2]. in xenopus oocytes coexpressed n-methyl-d-aspartate (nmda) receptor (nr) 1a with either nr2a, 2b or 2c, bd1008 inhibited nmda-activated membrane current responses with ic50 values of 62, 18 and 120 μm for nr1a/2a, nr1a/2b and nr1a/2c respectively, which were due to direct effects on the receptor channel complex [3].in mice, bd1008 (1 mg/kg) inhibited cocaine-induced locomotor activity with ed50 value increased from 6.50 mg/kg to 11.19 mg/kg [1].
References
[1]. mccracken ka, bowen wd, matsumoto rr. novel sigma receptor ligands attenuate the locomotor stimulatory effects of cocaine. eur j pharmacol, 1999, 365(1): 35-38.
[2]. john cs, gulden me, vilner bj, et al. synthesis, in vitro validation and in vivo pharmacokinetics of [125i]n-[2-(4-iodophenyl)ethyl]-n-methyl-2-(1-piperidinyl) ethylamine: a high-affinity ligand for imaging sigma receptor positive tumors. nucl med biol, 1996, 23(6): 761-766.
[3]. whittemore er, ilyin vi, woodward rm. antagonism of n-methyl-d-aspartate receptors by sigma site ligands: potency, subtype-selectivity and mechanisms of inhibition. j pharmacol exp ther, 1997, 282(1): 326-338.
