Description
PRE084 (138847-85-8) is an agonist of the σ receptor with selectivity for the σ1 subtype?(IC50’s: σ1 = 2.2nM, σ2 = 13091nM).1?PRE-084 has demonstrated neuroprotective/restorative effects in brain injury2,3?and neurodegenerative conditions4-7.
Definition
ChEBI: 1-phenyl-1-cyclohexanecarboxylic acid 2-(4-morpholinyl)ethyl ester is a member of morpholines.
Biological Activity
High affinity, selective σ 1 agonist (K i values are 2.2 and 13091 nM for σ 1 and σ 2 receptors respectively). Selective over PCP receptors (IC 50 > 100000 nM) and several other receptor systems. Produces antiamnesic and antitussive effects in vivo .
Biochem/physiol Actions
PRE-084 is a potent and highly selective σ1 opioid receptor agonist. It offers neuroprotection upon embolic stroke.
References
1) Su?et al.?(1991),?Sigma compounds derived from phencyclidine. Identification of PRE-084, a new selective sigma ligand; J. Pharmacol. Exp. Ther.?259?543
2) Griesmaier?et al.?(2012),?Neuroprotective effects of the sigma-1 receptor ligand PRE-084 against excitotoxic perinatal brain injury in newborn mice; Exp. Neurol.?237?388
3) Dong?et al.?(2016),?Sigma-1 Receptor Modulates Neuroinflammation After Traumatic Brain Injury; Cell Mol. Neurobiol.?36?639
4) Guzman-Lenis?et al.?(2009),?Selective sigma receptor agonist 2-(4-Morpholinethyl) 1-phenylcyclohexanecarboxylate (PRE084) promotes neuroprotection and neurite elongation through protein kinase C (PKC) signaling on motoneurons; Neuroscience?162?31
5) Hyrskyluoto?et al.?(2013),?Sigma-1 receptor agonist PRE084 in protective against mutant huntingtin-induced cell degeneration: involvement of calpastatin and the NF-κB pathway; Cell Death Dis.?4?e646
6) Francardo?et al.?(2014),?Pharmacological stimulation of sigma-1 receptors has neurorestorative effects in experimental parkinsonism; Brain?137(Pt7)?1998
7) Mancuso?et al.?(2012),?Sigma-1R agonist improves motor function and motoneuron survival in ALS mice; Neurotherapeutics?9?814
