κ Opioid Receptor/KOR Antagonist

Norbinaltorphimine dihydrochloride (nor-Binaltorphimine dihydrochloride; nor-BNI dihydrochloride) is a selective, long-acting competitive antagonist of the κ-opioid receptor. Norbinaltorphimine dihydrochloride blocks κ-opioid receptor-mediated analgesic effects, and inhibits butorphanol-induced changes in κ-opioid receptor binding kinetics, desensitization and down-regulation. Norbinaltorphimine dihydrochloride suppresses specific opioid withdrawal symptoms, precipitates withdrawal behaviors in butorphanol-dependent rats, and serves as a molecular probe for studying κ-opioid receptor-agonist interactions. Norbinaltorphimine dihydrochloride is applicable to research related to neurological disorders such as pain.

Naltrexone is an orally active, long-acting opioid receptor (opioid receptor) antagonist. Naltrexone blocks the euphoric effects of exogenous opioids and reduces alcohol craving by blocking opioid receptors (μ, κ, and δ) as well as opioid growth factor receptors. Low doses of Naltrexone are used to relieve chronic pain, treat inflammatory diseases and inhibit tumor growth, while high doses or continuous administration exert pro-inflammatory or pro-proliferative effects. Naltrexone relieves intractable pruritus caused by psoriasis, atopic dermatitis and other conditions, and its combination with Bupropion (HY-B0403) inhibits food craving, thereby reducing body weight.

Aticaprant (CERC-501) is a potent and centrally-penetrant kappa opioid receptor antagonist with a K_i of 0.807 nM.

nor-Binaltorphimine (Norbinaltorphimine; NorBNI) is a selective, long-acting competitive antagonist of the κ-opioid receptor. nor-Binaltorphimine blocks κ-opioid receptor-mediated analgesic effects, and inhibits butorphanol-induced changes in κ-opioid receptor binding kinetics, desensitization and down-regulation. nor-Binaltorphimine suppresses specific opioid withdrawal symptoms, precipitates withdrawal behaviors in butorphanol-dependent rats, and serves as a molecular probe for studying κ-opioid receptor-agonist interactions. nor-Binaltorphimine is applicable to research related to neurological disorders such as pain.

J-113397 is the first potent and selective nonpeptidyl ORL1 receptor antagonist (K_i: cloned human ORL1=1.8 nM) without any agonistic effects on other opioid receptors.

LY255582 is a pan-opioid antagonist and has high affinity for mu, delta, and kappa receptors (K_i: 0.4 nM, 5.2, 2.0 nM respectively). LY255582 can decrease food intake and body weight. LY255582 can be used for the research of obesity.

LY2444296 is an orally bioavailable, high-affinity and selective short-acting kappa opioid receptor (KOPR) antagonist, with a K_i value of ～1 nM. LY2444296 exhibits anti-anxiety like effects.

DIPPA hydrochloride is an irreversible, long-lasting, selective and high affinity κ-opioid receptor antagonist. DIPPA hydrochloride can be used for the research of anxiety and antidepressant.

JDTic is a blood-brain barrier-permeable κ-opioid receptor antagonist (K_i=0.02 nM) with favorable in vitro ADME properties. JDTic blocks agonist-mediated Gi and β-arrestin signaling pathways as well as analgesic effects by stabilizing the inactive conformation of hKOR and activating JNK. JDTic may also induce transient asymptomatic ventricular tachycardia. JDTic is widely applicable to studies related to depression, anxiety, stress-induced addictive behaviors, and nicotine withdrawal.

PF-04455242 is an orally bioavailable, blood-brain barrier-permeable κ-opioid receptor (KOR) inhibitor. PF-04455242 blocks in vivo effects induced by KOR and MOR agonists, and elicits KOR-independent outward currents in ventral tegmental area neurons. PF-04455242 promotes energy expenditure and activates the hypothalamic mTOR pathway. PF-04455242 attenuates stress-induced behavioral effects and produces antidepressant-like effects. PF-04455242 can be used in studies related to pain, depression, addictive disorders, and obesity induced by estrogen withdrawal.

AT-076 is an opioid pan antagonist at nociception, kappa, mu, and delta opioid receptors, with K_i values of 1.75 nM (NOP), 1.67 nM (MOP), 1.14 nM (KOP) and 19.6 nM (DOP), respectively.

LY2048978 is a non-selective opioid receptor antagonist with K_i of 0.287, 0.471 and 1.05 nM for human mu, kappa and delta opioid receptors in vitro, respectively. LY2048978 can be used in the research of major depressive disorder and alcohol use disorder.

SRI-22136 is a Delta Opioid Receptor (DOR) antagonist that can cross blood-brain barrier with a IC₅₀ of 0.42 nM. SRI-22136 does not have agonistic activity but antagonistic activity against DOR, MOR (IC₅₀ = 370 nM), KOR (IC₅₀ = 54 nM) and can avoid addiction/aversion effects. SRI-22136 can effectively inhibit the BACE1 activity induced by DADLE (a DOR agonist) (HY-105343) (IC₅₀ = 120 nM). SRI-22136 prevents completely Alzheimer’s-like pathology in mouse model. SRI-22136 can used for the study of Alzheimer’s disease.

Methocinnamox (M-CAM) a selective and long-acting μ-opioid receptor (MOR) antagonist with a K_i of 0.6 nM. Methocinnamox binds to the orthosteric site of the MOR in a pseudo-irreversible, non-covalent manner, resulting in prolonged receptor blockade that persists until new receptors are synthesized. Methocinnamox acts as a reversible antagonist at both the kappa-opioid receptor (KOR) (K_i = 4.9 nM) and delta-opioid receptor (DOR) (K_i = 2.2 nM), and it exhibits no intrinsic agonist activity at these receptors. Methocinnamox can be used to reverse and prevent opioid overdose and addiction.

Mu opioid receptor antagonist 9 is potent, selective and CNS-pentrant mu-opioid receptor (MOR) antagonist with a K_i of 77.3 nM. Mu opioid receptor antagonist 9 exhibits selectivity over kappa-opioid receptor (KOR), and delta-opioid receptor (DOR). Mu opioid receptor antagonist 9 effectively blocks the antinociceptive effects of psychoactive substances. Mu opioid receptor antagonist 9 can reverse psychoactive substances-induced respiratory depression in mice. Mu opioid receptor antagonist 9 can be used for the research of Opioid Use Disorder (OUD).

RU-24213 hydrochloride is a selective D-2 dopamine receptor agonist. RU-24213 hydrochloride is also a KAPPA-opioid receptor antagonist. RU-24213 hydrochloride induces stereotyped behaviors.

Axelopran (TD-1211) is an opioid receptor antagonist with pKi values of 9.8, 8.8 and 9.9 for human recombinant μ and δ receptors and guinea pig κ receptor, respectively.

Ondelopran (LY 2196044) is a non-selective opioid receptor antagonist. Ondelopran inhibits the release of dopamine in the nucleus accumbens induced by alcohol, reduces the rewarding effect of alcohol consumption, and lowers the craving. Ondelopran can be used for alcohol use disorder (AUD).