 Chemical Structure.png)
Physicochemical Properties
| Molecular Formula | C17H19NO |
| Molecular Weight | 253.34 |
| Exact Mass | 253.146 |
| CAS # | 13669-70-0 |
| Related CAS # | Nefopam hydrochloride;23327-57-3 |
| PubChem CID | 4450 |
| Appearance | Typically exists as solid at room temperature |
| Density | 1.1±0.1 g/cm3 |
| Boiling Point | 369.5±37.0 °C at 760 mmHg |
| Flash Point | 109.0±28.8 °C |
| Vapour Pressure | 0.0±0.8 mmHg at 25°C |
| Index of Refraction | 1.564 |
| LogP | 3.44 |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 2 |
| Rotatable Bond Count | 1 |
| Heavy Atom Count | 19 |
| Complexity | 274 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | CN1CCOC(C2=CC=CC=C2)C3=CC=CC=C3C1 |
| InChi Key | RGPDEAGGEXEMMM-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C17H19NO/c1-18-11-12-19-17(14-7-3-2-4-8-14)16-10-6-5-9-15(16)13-18/h2-10,17H,11-13H2,1H3 |
| Chemical Name | 5-methyl-1-phenyl-1,3,4,6-tetrahydro-2,5-benzoxazocine |
| HS Tariff Code | 2934.99.9001 |
| 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) |
Biological Activity
| ln Vitro | In SK-N-SH cells, nevopam (0.1-100 µM; 15 min) inhibits 22Na absorption in a concentration-dependent manner[1]. |
| ln Vivo | Nefopam (0-10 mg/kg; iv; single) shields mice from seizures brought on by electroshock[1]. In a vincristine-induced peripheral neuropathy model, neviropam (10, 30, 60 mg/kg; ip; single) exhibits a dose-dependent reduction in mechanical allodynia and a drop in neurokinin -1 receptor concentration[2]. |
| Cell Assay |
Cell Viability Assay[1] Cell Types: SK-N-SH cells Tested Concentrations: 0.1 -100 µM Incubation Duration: 15 min (preincubate) Experimental Results: Inhibited the uptake of 22Na with an IC50 value of 27 µM. |
| Animal Protocol |
Animal/Disease Models: Adult male NMRI mice (25-30 g; 6 to7weeks old; electroshock-induced seizures model)[1] Doses: 0-10 mg /kg Route of Administration: intravenous (iv) injection; single Experimental Results: Produced dose-dependent protection against maximal electroshock seizures in mice with an ED50 of 3.8 (2.9-5.1) mg/kg. Animal/Disease Models: Adult male mice (10weeks old; 25- 30 g; vincristine-induced peripheral neuropathy model)[2]. Doses: 10, 30, 60 mg/kg Route of Administration: intraperitoneal (ip) injection; single Experimental Results: Dramatically diminished the percentage of NK1 receptors in the spinal cord at dosage of 60 mg/kg. demonstrated a sustained increase in paw withdrawal threshold against mechanical stimuli. |
| Toxicity/Toxicokinetics |
Effects During Pregnancy and Lactation ◉ Summary of Use during Lactation Nefopam is not approved in the United States by the Food and Drug Administration. The amount of nefopam in breastmilk with usual maternal dosages is small. Nefopam does not appear to adversely affect the milk supply or the neurobehavioral scores of breastfed neonates. Breastfeeding is acceptable during maternal use of nefopam, although some recommend not using it after 48 hours postpartum. ◉ Effects in Breastfed Infants Sixty-six women who had cesarean section deliveries were two groups postpartum: intravenous (IV) nefopam 20 mg every 6 hours or IV acetaminophen 1 gram every 6 hours as well as IV ketoprofen 50 mg every 6 hours in both groups Neonatal neurobehavioral scores were recorded at 12, 24, 48, and 72 hours post-caesarean by a pediatrician blinded to the group allocation. No difference was found between the groups in the behavioral scores. ◉ Effects on Lactation and Breastmilk Sixty-six women who had cesarean section deliveries were two groups: IV nefopam 20 mg every 6 hours or IV acetaminophen 1 gram every 6 hours. All women received the same preoperative analgesia consisting of spinal bupivacaine, sufentanil, and morphine as well as intravenous ephedrine and phenylephrine to prevent hypotension. Postoperatively, all received IV oxytocin by infusion and IV ketoprofen 50 mg every 6 hours. Milk production was assessed by weighing the newborn before and after each breastfeed on days 2 and 3. No statistical differences were seen between the two groups in the weight difference before and after each feed, the newborn daily weight curve evolution, or the fall in weight between days 0 and 2. Mothers also rated their breast fullness to assess the onset of lactogenesis II; no difference was found between the two groups in the time to lactogenesis II. There was also no difference in serum prolactin between the groups. |
| References |
[1]. Nefopam blocks voltage-sensitive sodium channels and modulates glutamatergic transmission in rodents. Brain Res. 2004 Jul 9;1013(2):249-55. [2]. The Antiallodynic Effect of Nefopam on Vincristine-Induced Neuropathy in Mice. J Pain Res. 2020 Feb 7;13:323-329. [3]. Rediscovery of nefopam for the treatment of neuropathic pain. Korean J Pain. 2014 Apr;27(2):103-11. |
| Additional Infomation |
5-methyl-1-phenyl-3,4,5,6-tetrahydro-1H-2,5-benzoxazocine is a member of the class of benzoxazocines that is 3,4,5,6-tetrahydro-1H-2,5-benzoxazocine substituted by phenyl and methyl groups at positions 1 and 5 respectively. It is a benzoxazocine and a tertiary amino compound. Nefopam is under investigation for the prevention of Cholecystitis and Post Anaesthetic Shivering. Nefopam has been investigated for the prevention of Kidney Transplantation. Non-narcotic analgesic chemically similar to ORPHENADRINE. Its mechanism of action is unclear. It is used for the relief of acute and chronic pain. (From Martindale, The Extra Pharmacopoeia, 30th ed, p26) See also: Nefopam Hydrochloride (annotation moved to). |
Solubility Data
| 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 |
| 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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.9473 mL | 19.7363 mL | 39.4726 mL | |
| 5 mM | 0.7895 mL | 3.9473 mL | 7.8945 mL | |
| 10 mM | 0.3947 mL | 1.9736 mL | 3.9473 mL |