κ Opioid Receptor/KOR Modulator

Noribogaine hydrochloride is an orally active, blood-brain barrier permeable SERT inhibitor (IC₅₀=50-300 nM) and hERG channel blocker. Noribogaine hydrochloride enhances serotonergic transmission, activates the κ-opioid receptor (OPRK) G protein signaling pathway and inhibits β-arrestin recruitment. Meanwhile, Noribogaine hydrochloride blocks the μ-opioid receptor (OPRM) signaling pathway as well as ion channels associated with cardiac repolarization. Noribogaine hydrochloride induces neuritogenesis, upregulates GDNF mRNA expression, and modulates opioid tolerance. Noribogaine hydrochloride reduces alcohol-seeking behavior in experimental animals, and is widely used in studies related to depression, addiction, alcoholism, and cardiotoxicity.

Samidorphan-d5 (ALKS-33-d5) is is a deuterated compound of Samidorphan. Samidorphan is an orally active opioid system modulator that binds with high affinity to μ-opioid, κ-opioid, and δ-opioid receptors. Samidorphan is a μ-opioid receptor antagonist and a partial agonist at k-opioid and δ-opioid receptors. Samidorphan acts primarily as an opioid receptor antagonist in vivo.

Cyclazocine is a μ, δ, and κ opioid receptor modulator with K_i values of 0.32, 1.1, and 0.18 nM, respectively. Cyclazocine exhibits "mixed" pharmacological activities, acting as a μ-partial antagonist, κ-agonist, and low-affinity δ ligand. Cyclazocine shows antinociceptive activity in mice. Cyclazocine can be used in studies on psychoactive substance addiction.

KOR modulator-1 is a blood-brain barrier-permeable kappa opioid receptor (KOR) modulator. KOR modulator-1 induces antinociceptive effects without significant sedation or impairment of neuromuscular coordination. KOR modulator-1 can be used for the research of chronic pain.

Tyr-c [D-Lys-p-F-Phe-Phe-Asp]-D-Pro-NH2 is a multi-opioid receptor (Opioid Receptor) modulator, acting as a MOR/KOR agonist and a DOR antagonist. Tyr-c [D-Lys-p-F-Phe-Phe-Asp]-D-Pro-NH2 activates the G protein-mediated cAMP inhibitory pathway and β-arrestin2 recruitment pathway downstream of MOR, with an EC₅₀ of 159 nM for β-arrestin2 recruitment, an EC₅₀ of 1.1 nM for MOR-mediated calcium mobilization, and an EC₅₀ of 397 nM for KOR. Tyr-c [D-Lys-p-F-Phe-Phe-Asp]-D-Pro-NH2 exhibits potent analgesic activity in vivo. It can be used in studies related to opioid receptor function and analgesia.

6-Fluoro-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole is a ORL-1 receptor modulator. 6-Fluoro-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole regulates downstream pathways associated with nociception, cognition and physiological processes. 6-Fluoro-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole is used in the research of central nervous system diseases and pain-related disorders including anxiety, depression, Alzheimer's disease and attention deficit disorder.

MOR modulator-1 (compound 6) is a potent and selective μ opioid receptor (MOR) modulator. MOR modulator-1 exhibits improved opioid receptor selectivity, enhanced in vivo antagonistic effect, and overall fewer withdrawal symptoms compared to NAT (6α-configuration). MOR modulator-1 links with carboxamido linker μ, δ, γ with K_is of 0.25, 41.1, 1.30 nM, respectively_[1]

RM1490 (Compound 251) acts as an inhibitor of μ-opioid receptor (MOR) (IC₅₀ ≤ 300 nM), an activator of δ-opioid receptor (DOR) (EC₅₀ > 3000 nM), and an inhibitor of κ-opioid receptor (KOR) (IC₅₀ ≤ 300 nM). RM1490 is applicable to the research of neuropsychiatric disorders.