opioid receptor antagonist 1

Opioid receptor antagonist 1 (Compound 10) is an Orvinol-based antagonist of opioid receptors. It exhibits activity as an antagonist against the analgesic properties of morphine.

ORL1 antagonist 1 is an o antagonist of pioid receptor-like 1 (ORL1) (IC50 of 61 nM).

Unifiram is a nootropic agent.1It increases acetylcholine (ACh) release in the rat cerebral cortexin vivoand induces a long-lasting increase in the amplitude of field excitatory postsynaptic potentials (fEPSPs) in the rat hippocampal CA1 region (EC50= 27 nM). It does not bind to serotonin (5-HT), dopamine, muscarinic, nicotinic, adrenergic, glutamate, histamine, opioid, or GABA receptors at 1 μM. Unifiram (0.1 mg/kg) improves memory in non-memory-impaired rats in a social learning test.2It also prevents memory deficits induced by the anticholinergic agent scopolamine, nicotinic receptor antagonist mecamylamine, GABABreceptor agonist baclofen, or α2-adrenergic receptor agonist clonidine in the passive avoidance test in mice when administered at a dose of 0.01 mg/kg and prevents memory deficits induced by the AMPA/kainate glutamate receptor antagonist NBQX at 0.1 mg/kg.1 1.Romanelli, M.N., Galeotti, N., Ghelardini, C., et al.Pharmacological characterization of DM232 (unifiram) and DM235 (sunifiram), new potent cognition enhancersCNS Drug Rev.12(1)39-52(2006) 2.Ghelardini, C., Galeotti, N., Gualtieri, F., et al.The novel nootropic compound DM232 (unifiram) ameliorates memory impairment in mice and ratsDrug Develop. Res.56(1)23-32(2002)

LY2444296 (FP3FBZ) is an orally active and selective antagonist of kappa opioid receptor(Ki = 1 nM).

BTRX-335140 (CYM-53093) is a potent and selective orally active κ-opioid receptor (KOR) antagonist with antagonistic activity against κOR, μOR, and δOR with IC50 values of 0.8, 110, and 6500 nM, respectively.

Urotensin-II receptor antagonist-1 (compound 1) is a human Urotensin II receptor antagonist with low oral bioavailability (F=0-3% in rats) and a Ki of 16 nM in HEK293 cells expressing human recombinant UT receptors. It inhibits cytochrome P450 enzymes (IC50=0.75 μM for CYP2D6; 1.4 μM for CYP3A4), suppresses κ opioid receptors (EC50=3.2 μM), and targets cardiac sodium channels (Ki=2.5 μM).

Alvimopan dihydrate (ADL 8-2698 dihydrate) is a potent, selective, orally active, and reversible μ-opioid receptor antagonist with an IC50 of 1.7 nM. Highly selective for the μ-opioid receptor (Ki = 0.47 nM) over κ- and δ-opioid receptors (Kis = 100 and 12 nM, respectively), Alvimopan dihydrate can be used for research on postoperative ileus [1] [2] [3].

Naloxegol (NKTR-118; AZ-13337019) is an opioid receptor antagonist[1].

Deltorphin II is a peptide agonist of δ2-opioid receptors.1,2It is selective for δ-opioid receptors over μ- and κ-opioid receptors in radioligand bindings assays (Kis = 0.0033, >1, and >1 μM, respectively) and induces [35S]GTPγS binding in mouse brain membrane preparations (EC50= 0.034 μM). Deltorphin II (0.12 mg/kg) decreases the infarction zone:risk zone ratio in a rat model of myocardial ischemia-reperfusion injury induced by coronary occlusion, an effect that can be reversed by the δ2-opioid receptor antagonist naltriben but not the δ1-opioid receptor antagonist BNTX.3Intrathecal administration of deltorphin II (15 μg/animal) increases latency to withdraw in the paw pressure and tail-flick tests in rats.4 1.Raynor, K., Kong, H., Chen, Y., et al.Pharmacological characterization of the cloned κ-, δ-, and μ-opioid receptorsMol. Pharm.45(2)330-334(1994) 2.Scherrer, G., Befort, K., Contet, C., et al.The delta agonists DPDPE and deltorphin II recruit predominantly mu receptors to produce thermal analgesia: A parallel study of mu, delta and combinatorial opioid receptor knockout miceEur. J. Neurosci.19(8)2239-2248(2004) 3.Maslov, L.N., Barzakh, E.I., Krylatov, A.V., et al.Opioid peptide deltorphin II simulates the cardioprotective effect of ischemic preconditioning: role of δ2-opioid receptors, protein kinase C, and KATP channelsBull. Exp. Biol. Med.149(5)591-593(2010) 4.Labuz, D., Toth, G., Machelska, H., et al.Antinociceptive effects of isoleucine derivatives of deltorphin I and deltorphin II in rat spinal cord: A search for selectivity of delta receptor subtypesNeuropeptides32(6)511-517(1998)

Difelikefalin is a κ-opioid receptor (KOR) agonist.1It activates KOR in HEK293 cells expressing the human receptor (EC50= 0.16 nM in a transactivation assay) and inhibits forskolin-induced cAMP production in R1.G1 mouse thyoma cells (EC50= 0.048 nM). Difelikefalin is selective for KOR over the μ-opioid receptor (MOR; EC50= >1 μM in a transactivation assay). It reduces acetic acid-induced writhing, as well as scratching behavior induced by the KOR antagonist GNTI, in mice (ED50s = 0.07 and 0.05 mg/kg, respectively). 1.Schteingart, C.D., Menzaghi, F., Jiang, G., et al.Synthetic peptide amides(2008)

σ 1 Receptor/ μ Opioid receiver modulator 1 (Compound 44) is an effective σ 1 receptor antagonist (Ki=1.86 nM) and μ Opioid receptor agonists (Ki=2.1 nM). Opioid receptor modulator 1 shows potent analgesic activity, and can be used for the research of neuropathic pain.

SB-612111 hydrochloride is a potent, novel orphan receptor for opioid receptors (ORL-1) antagonist with high affinity for hORL-1 and a Ki value of 0.33 nM. SB-612111 hydrochloride is able to act on mu-receptor (Ki: 57.6 nM), κ SB-612111 hydrochloride effectively antagonized the nociceptive effects of Nociceptin in an acute pain model.

JTC-801 is a selective opioid receptor-like 1 (ORL1) receptor antagonist with an IC50 of 94 nM and weak inhibitory effects on δ, κ, and μ receptors.

Difelikefalin TFA is a κ-opioid receptor (KOR) agonist. It activates KOR in HEK293 cells expressing the human receptor (EC50 = 0.16 nM in a transactivation assay) and inhibits forskolin-induced cAMP production in R1.G1 mouse thyoma cells (EC50 = 0.048 nM). Difelikefalin TFA is selective for KOR over the μ-opioid receptor (MOR; EC50 = >1 µM in a transactivation assay). It reduces acetic acid-induced writhing, as well as scratching behavior induced by the KOR antagonist GNTI, in mice (ED50s = 0.07 and 0.05 mg/kg, respectively).

Difelikefalin HCl is a κ-opioid receptor (KOR) agonist. It activates KOR in HEK293 cells expressing the human receptor (EC50 = 0.16 nM in a transactivation assay) and inhibits forskolin-induced cAMP production in R1.G1 mouse thyoma cells (EC50 = 0.048 nM). Difelikefalin HCl is selective for KOR over the μ-opioid receptor (MOR; EC50 = >1 µM in a transactivation assay). It reduces acetic acid-induced writhing, as well as scratching behavior induced by the KOR antagonist GNTI, in mice (ED50s = 0.07 and 0.05 mg/kg, respectively).

ADL 08-0011 is an active metabolite of the μ-opioid receptor antagonist alvimopan. It is produced from alvimopan via amide hydrolysis by gut microbiota. ADL 08-0011 is a μ-opioid receptor antagonist (Ki = 0.25 nM). It is selective for μ-opioid receptors over κ- and δ-opioid receptors (Kis = 15.8 and 31.6 nM, respectively). ADL 08-0011 inhibits endomorphin 1-induced inhibition of electrically induced contraction of isolated guinea pig ileum (pA2 = 9.4). In vivo, ADL 08-0011 (0.03-1 mg/kg) reverses loperamide-induced delayed gastric emptying in a rat model of castor oil-induced diarrhea.

(S,S)-J-113397, an isomer of J-113397, is an opioid receptor antagonist [1].

UFP-101 TFA is a potent, selective, and competitive N/OFQ peptide (NOP) receptor antagonist with a pKi value of 10.24, showing over 3000-fold selectivity against δ, μ, and κ opioid receptors, and exhibits antidepressant-like effects [1] [2].

CTOP TFA, a potent and highly selective μ-opioid receptor antagonist, antagonizes acute analgesic effects and hypermotility, while enhancing extracellular dopamine levels in the nucleus accumbens. It also dose-dependently increases locomotor activity [1] [2].

CTAP TFA, a potent and highly selective μ opioid receptor antagonist that effectively crosses the blood-brain barrier, exhibits a significant inhibition concentration (IC50) of 3.5 nM. It demonstrates extraordinary selectivity, being over 1200-fold more specific to μ opioid receptors than to δ opioid (IC50 = 4500 nM) and somatostatin receptors. This compound is primarily leveraged for researching L-DOPA-induced dyskinesia (LID) and opiate overdose or addiction [1] [2].

Compound 24, also known as Mu opioid receptor antagonist 7, is a potent, centrally-acting µ-opioid receptor (µOR) antagonist with an inhibitory concentration (IC50) of 29 ± 3.0 nM. It is valuable for pain and opioid use disorder research [1].

Icalcaprant is a kappa-opioid receptor antagonist (KOR-A) that effectively blocks the kappa opioid receptors in the brain, which are implicated in various neurological and psychiatric conditions [1].

CSD-CH2(1,8)-NH2 is a selective and competitive kappa-opioid receptor (KOR) antagonist with a K i of 6.8 nM. It inhibits calcium mobilization in dorsal root ganglion (DRG) neurons and counters the antinociceptive effect of U50,488, making it useful for research into neuropsychiatric disorders [1].

6β-Naltrexol functions as a potent and peripherally selective opioid receptor antagonist. Unlike central-acting opioid antagonists, 6β-Naltrexol is restricted primarily to peripheral tissues, which allows it to counteract opioid-mediated side effects such as opioid-induced constipation while minimizing central nervous system interactions. 6β-Naltrexol is therefore relevant in reseaches in peripheral opioid effects.