Sigma 1 Receptor Agonist

PRE-084 hydrochloride is a highly selective σ1 receptor (S1R) agonist, with an IC₅₀ of 44 nM. PRE-084 hydrochloride exhibits good neuroprotective effects, can improve motor function and motor neuron survival in mice. PRE-084 hydrochloride also can ameliorate myocardial ischemia-reperfusion injury in rats by activating the Akt-eNOS pathway.

Siramesine (Lu 28-179) hydrochloride is a potent sigma-2 receptor agonist. Siramesine hydrochloride has a subnanomolar affinity for sigma-2 receptors (IC₅₀=0.12 nM) and exhibits a 140-fold selectivity for sigma-2 receptors over sigma-1 receptors (IC₅₀=17 nM). Siramesine hydrochloride triggers cell death through destabilisation of mitochondria, but not lysosomes. Anti-cancer activity.

S1R agonist 3 is a potent, selective and brain-penetrant sigma-1 receptor (S1R) agonist with a K_i of 1.5 nM. S1R agonist 3 reduces hyperlocomotion in wfs1abKO zebrafish larvae without affecting locomotion in wildtype wfs1abWT zebrafish larvae. S1R agonist 3 reverses Aβ_25-35 (HY-P0128)-induced learning and memory impairments. S1R ligand 1 can be used for the research of Alzheimer’s disease.

Blarcamesine hydrochloride (Anavex 2-73) is a Sigma-1 Receptor agonist with an IC₅₀ of 860 nM.

Cutamesine (SA4503) dihydrochloride is a potent and selective sigma 1 receptor agonist with an IC₅₀ of 17.4 nM in guinea pig brain membranes. Cutamesine dihydrochloride shows >100-fold less affinity for the sigma 2 receptor (IC₅₀ of 1784 nM). Cutamesine dihydrochloride has antidepressant effects.

Cutamesine (SA4503) is a potent and selective sigma 1 receptor agonist with an IC₅₀ of 17.4 nM in guinea pig brain membranes. Cutamesine shows >100-fold less affinity for the sigma 2 receptor (IC₅₀ of 1784 nM). Cutamesine has antidepressant effects.

Blarcamesine is an orally bioavailable Sigma-1 receptor agonist and muscarinic receptor modulator, with anticonvulsant, anti-amnesic, neuroprotective and antidepressant properties. Blarcamesine ameliorates neurologic impairments in a mouse model of Rett syndrome.

Ditolylguanidine (1,3-Di-o-tolylguanidine) is an agonist of sigma receptor (σ1/σ2 receptor) with K_i values of 69 and 21 nM for σ1 and σ2 receptors, respectively. Ditolylguanidine effectively inhibits the growth of small cell lung cancer cells. Ditolylguanidine can be used for the research of lung cancer.

Siramesine (Lu 28-179) is a potent sigma-2 receptor agonist. Siramesine has a subnanomolar affinity for sigma-2 receptors (IC₅₀=0.12 nM) and exhibits a 140-fold selectivity for sigma-2 receptors over sigma-1 receptors (IC₅₀=17 nM). Siramesine triggers cell death through destabilisation of mitochondria, but not lysosomes. Anti-cancer activity.

Dimemorfan phosphate is a sigma 1 receptor agonist, used as a potent antitussive.

Pentoxyverine (Carbetapentane) citrate is an orally active and blood-brain barrier permeability sigma-1 receptor agonist, with K_is of 41 nM, 894 nM and 75 nM for σ1, σ2 and guinea-pig brain membrane σ1, respectively. Pentoxyverine citrate is a muscarinic antagonist. Pentoxyverine citrate is a potent antitussive, anticonvulsant, and spasmolytic agent. Pentoxyverine citrate can be used for inhibiting bronchial interceptor, weakening of cough reflex, bronchial smooth muscle relaxation and reduction of airway resistance.

Pentoxyverine (Carbetapentane) is an orally active sigma-1 receptor agonist, with K_is of 41 nM, 894 nM and 75 nM for σ1, σ2 and guinea-pig brain membran σ1, respectively. Pentoxyverine is a muscarinic antagonist. Pentoxyverine is a potent antitussive, anticonvulsant, and spasmolytic agent. Pentoxyverine can be used for inhibiting bronchial interceptor, weakening of cough reflex, bronchial smooth muscle relaxation and reduction of airway resistance.

4-IBP is a selective σ₁ receptor agonist with high affinity for the σ₁ receptor (K_i =1.7 nM) and moderate affinity for the σ₂ receptor (K_i = 25.2 nM). 4-IBP can make cancer cells more sensitive to the cytotoxic effects of pro-apoptotic and pro-autophagic compounds. 4-IBP significantly reduces the migration ability of a variety of cancer cells. 4-IBP is mainly used in glioblastoma, non-small cell lung cancer and prostate cancer research.

E1R is a positive allosteric modulator of sigma-1 receptors (Sig1R PAM) with cognition-enhancing activity.

S1R agonist 1 (Compound 6b) is a selective S1R agonist with K_is of 0.93 nM and 72 nM for S1R and S2R, respectively. S1R agonist 1 exhibits neuroprotection against ROS and NMDA-induced neurotoxicity.

UKH-1114 is a selective TMEM97 (a sigma-2 receptor) agonist with a K_i values of 1279 and 46 nM for σ1R and σ2R/TMEM97, respectively. UKH-1114 exhibits exceptional selectivity with negligible affinity for over 50 other receptors and channels. UKH-1114 effectively relieves spared nerve injury (SNI)-induced mechanical hypersensitivity with a long-lasting duration and without motor impairment. UKH-1114 can be used for neuropathic pain research.

S1R agonist 2 (Compound 8b) is a selective S1R agonist with K_is of 1.1 nM and 88 nM for S1R and S2R, respectively. S1R agonist 2 exhibits neuroprotection against ROS and NMDA-induced neurotoxicity.

BS148 is a selective sigma-2 receptor (S2R) agonist with a K_i 20 nM. BS148 shows >80-fold selective for S2R than S1R. BS148 activates the endoplasmic reticulum stress response through the upregulation of protein kinase R-like ER kinase (PERK), activating transcription factor 4 (ATF4) genes, and C/EBP homologous protein (CHOP). BS148 induces apoptosis in melanoma cell. BS148 downregulates genes related to the cholesterol pathway and activates the MAPK signaling pathway. BS148 can be used for the study of melanoma.

S1R agonist/BChE-IN-1 (Compound 7c) is a S1R (IC₅₀: 19 nM) agonist and selective BChE (IC₅₀: 37 nM for hBChE) inhibitor. S1R agonist/BChE-IN-1 can be used in the research of Alzheimer's disease.

Oxeladin is an orally active and brain-penetrant cough suppressant as well as a selective sigma 1 receptor agonist (K_i = 25 nM). Oxeladin can be used for pulmonary diseases and stroke research.