1-[2-(3,4-Dichlorophenyl)ethyl]-4-Methylpiperazine Dihydrochloride

BD1063 (206996-13-6) is potent and selective sigma-1 antagonist (IC50’s: σ1 = 9nM, σ2 = 449nM).1BD1063 abolished mechanical and thermal hyperalgesia in mice with carrageenan-induced acute inflammation by enhancing the action of endogenous opioid peptides of immune origin in a σ1 dependent manner.2BD1063 potentiated μ-opioid antinociception in mice in a sigma-dependent manner.3BD-1063 has been used in animal models to successfully treat compulsive eating4and excessive ethanol drinking5.

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The novel σ receptor ligands

BD 1063 dihydrochloride has been used as a sigma-1 receptor (S1R) antagonist:

• to study the in vitro and in vivo protective action of S1R against ferroptosis in hepatocellular carcinoma cells
• in a comparative evaluation of its anti-hyperalgesic action with that of the effects of N-(2-morpholin-4-yl-ethyl)-2-(1-naphthyloxy) acetamide (NMIN) in a chronic constriction injury model (CCI)
• to study the contribution of sigma receptors inhibition to the neuroprotective effects of memantine against amyloid-beta (Aβ)-induced neurotoxicity in SH-SY5Y cells

BD 1063 is a potent sigma(1) receptor antagonist; approximately 50-fold selective for sigma-1 over sigma-2 and 100-fold or more selective over 9 other tested neurotransmitter receptors. BD 1063 has been shown to antagonize cocaine efffects.

BD1063 dose-dependently reduces ethanol self-administration in sP rats (3.3-11 mg/kg) and withdrawn, dependent Wistar rats (4-11 mg/kg) at doses that does not modify mean ethanol self-administration in non-dependent Wistar controls. BD1063 also reduces the breakpoints of sP rats to work for ethanol under a progressive-ratio reinforcement schedule. BD1063 dose-dependently reduces binge-like eating and the regularity of food responding, and blocks the increased eating rate in Palatable rats. In the light/dark conflict test, BD1063 antagonizes the increased time spent in the aversive compartment and the increased intake of the palatable diet, without affecting motor activity. The administration of BD1063 30 minutes before each paclitaxel dose prevents the development of cold and mechanical allodynia in WT mice. Moreover, the acute administration of BD1063 dose dependently reverses both types of paclitaxel-induced allodynia.

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[1] RAE R. MATSUMOTO . Characterization of two novel σ receptor ligands: antidystonic effects in rats suggest σ receptor antagonism[J]. European journal of pharmacology, 1995, 280 3: Pages 301-310. DOI:10.1016/0014-2999(95)00208-3
[2] MIGUEL A TEJADA. Sigma-1 receptors control immune-driven peripheral opioid analgesia during inflammation in mice.[J]. Proceedings of the National Academy of Sciences of the United States of America, 2017, 114 31: 8396-8401. DOI:10.1073/pnas.1620068114
[3] CRISTINA SÁNCHEZ-FERNÁNDEZ. Modulation of peripheral μ-opioid analgesia by σ1 receptors.[J]. ACS Applied Electronic Materials, 2014: 32-45. DOI:10.1124/jpet.113.208272
[4] PIETRO COTTONE. Antagonism of Sigma-1 Receptors Blocks Compulsive-Like Eating[J]. Neuropsychopharmacology, 2012, 37 12: 2593-2604. DOI:10.1038/npp.2012.89
[5] VALENTINA SABINO. The σ-Receptor Antagonist BD-1063 Decreases Ethanol Intake and Reinforcement in Animal Models of Excessive Drinking[J]. Neuropsychopharmacology, 2008, 34 6: 1482-1493. DOI:10.1038/npp.2008.192