SA-4503,1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine dihydrochloride

SA4503 (165377-44-6) is a potent and selective sigma 1 agonist (σ1 IC50= 17.4 nM, σ2 IC50= 1784 nM).1It has been investigated as a cognition enhancer2,3, antidepressant4,5, anti-addiction agent6, and neuroprotectant7-10.

SA 4503 Dihydrochloride is a novel and selective σ1 receptor agonist.

SA4503 is a high affinity, orally active non-opioid intracellular receptor sigma-1 (σ1R) selective agonist (IC50 = 17.4 nM against 200 nM (+)-pentazocine for binding σ1R), exhibiting ~100-fold less affinity for the sigma 2 receptor subtype (σ2R) and little or no affinity toward 36 other receptors, ion channels and second messenger systems. Oral administration is reported to elicit cerebral acetylcholine (ACh) release in rat frontal cortex and hippocampus (5-20 mg/kg p.o.) and reduce immobility time in a mouse forced swimming test (Immobility time = 214.8 s without vs. 111.6 s with 1.0 mg/kg oral dosage).

Sigma 1 Receptor

Desiccate at RT

[1] KIYOSHI MATSUNO. Binding properties of SA4503, a novel and selective σ1 receptor agonist[J]. European journal of pharmacology, 1996, 306 1: Pages 271-279. DOI:10.1016/0014-2999(96)00201-4
[2] SA4503, a novel cognition enhancer with sigma 1 agonistic properties
[3] TOMIHISA NIITSU K H Masaomi Iyo. Sigma-1 receptor agonists as therapeutic drugs for cognitive impairment in neuropsychiatric diseases.[J]. Current pharmaceutical design, 2012, 18 7: 875-883. DOI:10.2174/138161212799436476
[4] G SKUZA  Z R. A potential antidepressant activity of SA4503, a selective sigma 1 receptor agonist.[J]. Behavioural Pharmacology, 2002, 13 7: 537-543. DOI:10.1097/00008877-200211000-00003
[5] GUILLAUME LUCAS. Further evidence for an antidepressant potential of the selective sigma1 agonist SA 4503: electrophysiological, morphological and behavioural studies.[J]. International Journal of Neuropsychopharmacology, 2008, 11 4: 485-495. DOI:10.1017/s1461145708008547
[6] TOMOHISA MORI. Inhibitory effects of SA4503 on the rewarding effects of abused drugs.[J]. Addiction Biology, 2014, 19 3: 362-369. DOI:10.1111/j.1369-1600.2012.00488.x
[7] MINAKO NAKAZAWA  Shiro M  Kiyoshi Matsuno. Activation of σ1 receptor subtype leads to neuroprotection in the rat primary neuronal cultures[J]. Neurochemistry international, 1998, 32 4: Pages 337-343. DOI:10.1016/s0197-0186(97)00105-8
[8] KARSTEN RUSCHER. The sigma-1 receptor enhances brain plasticity and functional recovery after experimental stroke.[J]. ACS Central Science, 2011: 732-746. DOI:10.1093/brain/awq367
[9] KARSTEN RUSCHER. Effects of the sigma-1 receptor agonist 1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)-piperazine dihydro-chloride on inflammation after stroke.[J]. ACS Applied Bio Materials, 2012: e45118. DOI:10.1371/journal.pone.0045118
[10] DAISUKE YAMASHITA. Neuroprotective effects of cutamesine, a ligand of the sigma-1 receptor chaperone, against noise-induced hearing loss[J]. Journal of Neuroscience Research, 2015, 93 5: 788-795. DOI:10.1002/jnr.23543