| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg | |||
| 10mg | |||
| Other Sizes |
| Targets |
kappa3-Opioid Receptor (agonist), micro-Opioid Receptor (partial agonist), delta-Opioid Receptor (partial agonist), and NOP Receptor (ORL1, antagonist). Naloxone benzoylhydrazone is a mixed-opioid ligand with a unique pharmacological profile: it is a prototype agonist for the kappa3-opioid receptor subtype, a partial agonist at micro and delta receptors, and an antagonist at the NOP receptor. This complex receptor activity profile makes it a valuable tool for dissecting the contributions of different opioid receptor subtypes in various physiological and pathophysiological processes.
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| ln Vitro |
Naloxone benzoylhydrazone, with a maximal action (Emax) comparable to that of the MOR agonist DAMGO, at the mu-opioid receptor (MOR), decreases cyclic AMP buildup (pEC50=8.74) and promotes [35S]GTPγS binding (pEC50=8.59) [1]. Naloxone benzoylhydrazone enhances [35S]GTPγS binding (pEC50=9.70) and inhibits the production of cyclic AMP (pEC50=9.45) at the kappa-opioid receptor (KOR) [1]. Naloxone benzoylhydrazone promotes [35S]GTPγS binding (pEC50=8.49) and inhibits cyclic AMP production (pE50=8.61) in CHO cells expressing delta-opioid receptors (DOR) [1].
Naloxone benzoylhydrazone is a mixed agonist/antagonist. It is a prototype kappa3-opioid receptor agonist, a partial agonist at the cloned micro and delta opioid receptors, and an antagonist at the opioid-like NOP receptor (ORL1). The compound binds to multiple opioid receptor subtypes with varying affinities. Its unique receptor activity profile distinguishes it from traditional opioid agonists (e.g., morphine, kappa agonists) and antagonists (e.g., naloxone). |
| ln Vivo |
A biphasic curve was shown in analgesia tests conducted in mice by comparing fixed dosages of morphine with escalating doses of naloxone benzoylhydrazone. At dosages as low as 1 μg/kg, naloxone benzoylhydrazone can partially counteract the analgesic effects of morphine. Morphine analgesia was nevertheless inhibited by higher dosages of naloxone benzoylhydrazone in a dose-dependent manner, and it was totally counteracted by the 1 mg/kg dose. The analgesic effect is restored when the dose of naloxone benzoylhydrazone is increased above 1 mg/kg. When given to mice alone, naloxone benzoylhydrazone elicited a comparable analgesic response and was also effective in rats. Excellent oral action characterizes naloxone benzoylhydrazone, which in mice has analgesic effects comparable to subcutaneous injection. Low-dose naloxone benzoylhydrazone not only prevents the analgesic effects of morphine but also fully opposes its fatal effects, promotes withdrawal in morphine-dependent mice, and partially reverses the inhibitory effects of morphine on gastrointestinal transit in mice. [4].
Naloxone benzoylhydrazone has been used in animal models to study the role of kappa3-opioid receptors in pain modulation, gastrointestinal motility, and other physiological processes. It has been shown to produce antinociceptive (pain-relieving) effects in some models, likely mediated through the kappa3 receptor. At higher doses, it may antagonize micro-opioid receptor-mediated effects (like naloxone). The compound is not used clinically but is a research tool. |
| Enzyme Assay |
Radioligand binding assays for opioid receptors are performed using membrane preparations from CHO or HEK-293 cells expressing human micro, delta, kappa, or NOP receptors, or from guinea pig brain (rich in kappa3 sites). Membranes (50-100 microg protein) are incubated with appropriate radioligands: [3H]DAMGO (micro), [3H]DPDPE (delta), [3H]U69,593 (kappa), [3H]nociceptin (NOP), or [3H]ethylketocyclazocine (kappa3). Varying concentrations of Naloxone benzoylhydrazone (0.01-1000 nM) are added, and incubation is carried out for 60-90 minutes at 25degC. Nonspecific binding is determined with excess cold ligand. Bound and free radioligands are separated by filtration through GF/B filters. Ki values are calculated.
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| Cell Assay |
Not applicable (no direct cell-based activity assays; used in receptor binding and functional assays in transfected cells). For functional studies, CHO or HEK-293 cells expressing micro, delta, kappa, or NOP receptors are used. For agonist activity at micro/delta/kappa receptors, agonist-mediated inhibition of forskolin-stimulated cAMP accumulation is measured using a cAMP ELISA or HTRF assay. For antagonism at NOP receptors, the compound is tested for its ability to block the nociceptin-mediated inhibition of cAMP accumulation. EC50 values for agonist activity and IC50 values for antagonist activity are calculated.
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| Animal Protocol |
Not applicable (primarily an in vitro pharmacological tool). Naloxone benzoylhydrazone is not typically administered in animal efficacy studies for therapeutic purposes; it is used as a research tool to probe opioid receptor pharmacology. For receptor characterization studies, the compound can be administered intracerebroventricularly (ICV) or intraperitoneally (i.p.) to rodents to assess its effects on pain responses in the tail-flick, hot plate, or formalin tests. However, it is not a standard in vivo tool.
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| ADME/Pharmacokinetics |
Naloxone benzoylhydrazone has a molecular weight of approximately 445.5 g/mol. The compound is a naloxone derivative with a hydrazone modification at the 6-position. It is typically stored as a lyophilized powder at -20degC, protected from light. Solubility is limited; DMSO is recommended for stock solutions. Naloxone benzoylhydrazone is expected to cross the blood-brain barrier due to its structural similarity to naloxone. No detailed human PK data are available.
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| Toxicity/Toxicokinetics |
Naloxone benzoylhydrazone is a research compound and is not approved for human therapeutic use. Toxicity data are limited. As an opioid receptor ligand, high doses may produce opioid-like effects (analgesia, sedation, respiratory depression) mediated through kappa3 agonism or partial micro agonism. The compound is not known to be hepatotoxic or nephrotoxic at typical research doses. Standard laboratory safety precautions should be used when handling.
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| References | |
| Additional Infomation |
Naloxone benzoylhydrazone (NalBzoH) is a mixed-opioid ligand that serves as a prototype agonist for the kappa3-opioid receptor subtype. The existence of the kappa3 receptor is controversial, and Naloxone benzoylhydrazone has been used as a key pharmacological tool to define and characterize this putative opioid receptor subtype. The compound also has activity at micro, delta, and NOP receptors, making it a complex but valuable research tool for studying opioid receptor pharmacology, receptor crosstalk, and the development of novel analgesics with reduced side effect profiles.
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| Molecular Formula |
C26H27N3O4
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|---|---|
| Molecular Weight |
445.51028
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| Exact Mass |
445.2
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| CAS # |
119630-94-3
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| PubChem CID |
9601084
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.44g/cm3
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| Index of Refraction |
1.722
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| LogP |
2.847
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
33
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| Complexity |
841
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| Defined Atom Stereocenter Count |
4
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| SMILES |
C=CCN1CC[C@]23[C@@H]4/C(=N/NC(=O)C5=CC=CC=C5)/CC[C@]2([C@H]1CC6=C3C(=C(C=C6)O)O4)O
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| InChi Key |
AKXCFAYOTIEFOH-XTNAHFASSA-N
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| InChi Code |
InChI=1S/C26H27N3O4/c1-2-13-29-14-12-25-21-17-8-9-19(30)22(21)33-23(25)18(10-11-26(25,32)20(29)15-17)27-28-24(31)16-6-4-3-5-7-16/h2-9,20,23,30,32H,1,10-15H2,(H,28,31)/b27-18+/t20-,23+,25+,26-/m1/s1
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| Chemical Name |
N-[(E)-[(4R,4aS,7aR,12bS)-4a,9-dihydroxy-3-prop-2-enyl-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-ylidene]amino]benzamide
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2446 mL | 11.2231 mL | 22.4462 mL | |
| 5 mM | 0.4489 mL | 2.2446 mL | 4.4892 mL | |
| 10 mM | 0.2245 mL | 1.1223 mL | 2.2446 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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