Biological Activity
brl 52537 hydrochloride is a potent and selective agonist of κ/μ-opioid receptor with ki value of 0.24 nm for κ-opioid receptor [1].the κ-opioid receptor (kor) is a type of opioid receptor for opioid peptide dynorphin and controls addiction. also, kor plays an important role in stress, anxiety, anhedonia, depression and increased drug-seeking behavior.brl 52537 hydrochloride is a potent and selective κ/μ-opioid receptor agonist. in the mouse tail flick model, brl 52537 showed antinociception with ed50 value of 0.05 mg/kg, which was 25 times more potent than morphine [1]. in wt male mice with middle cerebral artery occlusion, brl 52537 significantly decreased infarct volumes at 72 h of reperfusion. however, brl 52537 had no effect in neuronal no synthase null mutants (nnos-/-) mice or in the wt female mice. these results suggested that brl 52537 exhibited neuroprotection through inhibition of ischemia-evoked no production and nnos activity [2]. in adult rat dorsal root ganglia (drgs), brl 52537 inhibited tetrodotoxin-resistant (ttx-r) sodium currents in an opioid receptor-independent way, which also contributed to the antinociceptive effects [3]. in rats with cerebral ischemia/reperfusion (i/r) injury, brl52537 inhibited neuronal apoptosis and brain damage. also, brl52537 increased the level of phosphorylated stat3 and reduced caspase-3 expression [4].
References
[1]. vecchietti v, giordani a, giardina g, et al. (2s)-1-(arylacetyl)-2-(aminomethyl)piperidine derivatives: novel, highly selective kappa opioid analgesics. j med chem, 1991, 34(1): 397-403.
[2]. zeynalov e, nemoto m, hurn pd, et al. neuroprotective effect of selective kappa opioid receptor agonist is gender specific and linked to reduced neuronal nitric oxide. j cereb blood flow metab, 2006, 26(3): 414-420.
[3]. su x, castle na, antonio b, et al. the effect of kappa-opioid receptor agonists on tetrodotoxin-resistant sodium channels in primary sensory neurons. anesth analg, 2009, 109(2): 632-640.
[4]. fang s, xu h, lu j, et al. neuroprotection by the kappa-opioid receptor agonist, brl52537, is mediated via up-regulating phosphorylated signal transducer and activator of transcription-3 in cerebral ischemia/reperfusion injury in rats. neurochem res, 2013, 38(11): 2305-2312.
