Naloxone CAS 465-65-6
Introduction：Basic information about Naloxone CAS 465-65-6, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
Naloxone Basic information
| Product Name: | Naloxone |
| Synonyms: | 12-allyl-7,7a,8,9-tetrahydro-3,7a-dihydroxy-4ah-8,9c-iminoethanophenanthro(4,5;12-allyl-7,7a,8,9-tetrahydro-3,7a-dihydroxy-4ah-8,9c-iminoethanophenanthro[4,5;17-allyl-4,5alpha-epoxy-3,14-dihydroxy-morphinan-6-on;17-allyl-4,5-alpha-epoxy-3,14-dihydroxymorphinan-6-one;17-allyl-4,5alpha-epoxy-3,14-dihydroxymorphinan-6-one;1-n-allyl-14-hydroxynordihydromorphinone;1-n-allyl-7,8-dihydro-14-hydroxynormorphinone;4,5-alpha-epoxy-3,14-dihydroxy-17-(2-propenyl)-morphinan-6-on |
| CAS: | 465-65-6 |
| MF: | C19H21NO4 |
| MW: | 327.37 |
| EINECS: | 207-365-7 |
| Product Categories: | Isotopically Labeled Pharmaceutical Reference Standard;AMPLIMEXON |
| Mol File: | 465-65-6.mol |
Naloxone Chemical Properties
| Melting point | 184° (Lewenstein), 177-178° (Sankyo Co.) |
| alpha | D20 -194.5° (c = 0.93 in CHCl3) |
| Boiling point | 465.27°C (rough estimate) |
| density | 1.2223 (rough estimate) |
| refractive index | 1.5000 (estimate) |
| Fp | 9℃ |
| storage temp. | 2-8°C |
| solubility | Chloroform (Slightly, Heated, Sonicated), DMSO (Slightly), Methanol (Slightly), |
| form | Solid |
| pka | pKa 7.94/7.82(H2O,t =20/37,I<0.01) (Uncertain) |
| color | White to Off-White |
| InChI | 1S/C19H21NO4/c1-2-8-20-9-7-18-15-11-3-4-12(21)16(15)24-17(18)13(22)5-6-19(18,23)14(20)10-11/h2-4,14,17,21,23H,1,5-10H2/t14-,17+,18+,19-/m1/s1 |
| InChIKey | UZHSEJADLWPNLE-GRGSLBFTSA-N |
| SMILES | Oc1ccc2C[C@H]3N(CC[C@@]45[C@@H](Oc1c24)C(=O)CC[C@@]35O)CC=C |
| EPA Substance Registry System | Morphinan-6-one, 4,5-epoxy-3,14-dihydroxy-17-(2-propenyl)-, (5.alpha.)- (465-65-6) |
Safety Information
| Hazard Codes | F,T |
| Risk Statements | 11-23/24/25-39/23/24/25 |
| Safety Statements | 7-16-36/37-45 |
| RIDADR | UN1230 - class 3 - PG 2 - Methanol, solution |
| WGK Germany | 3 |
| HS Code | 2939190000 |
| Storage Class | 3 - Flammable liquids |
| Hazard Classifications | Acute Tox. 3 Dermal Acute Tox. 3 Inhalation Acute Tox. 3 Oral Flam. Liq. 2 STOT SE 1 |
| Hazardous Substances Data | 465-65-6(Hazardous Substances Data) |
| Toxicity | An opiate antagonist devoid of agonist activity exceptfor mild, specific effects at very high doses. Naloxone displays ahigh affinity for the μ-opioid receptor, a lesser affinity for the kopioidreceptor and has some affinity for δ-opioid receptor subtypes.Naloxone produces a rapid and profound reversal of the effects of opioid administration (e.g., 1 mg, i.v., blocks the effectsof 25 mg of heroin). Naloxone also antagonizes the analgesiainduced by placebo, acupuncture, and stress, and in animals thehypotension due to hypovolemia or spinal cord injury. Naloxonehas a short half-life (about 1 h in plasma) and is not administeredorally because of rapid, “first-pass” metabolism. |
| Description | It is worth mentioning that N-allylic substitution in a number of morphine derivatives, asa rule, leads to antagonistic properties. Naloxone is a few times stronger than nalorphineas an antagonist. It blocks opiate receptors. It eliminates central and peripheral action ofopioids, including respiratory depression. Naloxone is used upon overdose of narcoticanalgesics. |
| Originator | Narcan,Du Pont,US,1971 |
| Uses | Naloxone is a specific opioid antagonist. Narcotic antagonist. |
| Uses | antineoplastic |
| Definition | ChEBI: A synthetic morphinane alkaloid that is morphinone in which the enone double bond has been reduced to a single bond, the hydrogen at position 14 has been replaced by a hydroxy group, and the methyl group attached to the nitrogen has been replaced by an alll group. A specific opioid antagonist, it is used (commonly as its hydrochloride salt) to reverse the effects of opioids, both following their use of opioids during surgery and in cases of known or suspected opioid overdose. |
| Manufacturing Process | 10 grams of 14-hydroxydihydromorphinone (oxymorphone) was convertedinto its diacetate by warming it on the steam bath with 80 cc of aceticanhydride for about 2 hours. The acetic anhydride was removed on the waterbath under a vacuum of about 30 mm absolute pressure. The melting point ofthe residue was 220°C. The residue was taken up in 100 cc of chloroform. Anequal amount by weight of cyanogen bromide was added and the mixture wasrefluxed at about 60°C for about 5 hours. After refluxing, the mixture waswashed with 100 cc of a 5% aqueous hydrochloric acid solution, dried oversodium sulfate and the chloroform removed by evaporation under a vacuum ofabout 30 mm. The residue had a melting point of 240°C. The residue was then heated at about 90°C for 16 hours on a steam bath with300 cc of 20% aqueous hydrochloric acid solution, and treated with a smallamount, e.g., 1 gram of charcoal. The hydrochloric acid was then removedunder a vacuum of 15 mm, the residue dissolved in 30 cc of water andprecipitated by the addition of 2.4 cc of concentrated aqueous ammonia. Theprecipitate was filtered off and dried. It consists of 14-hydroxydihydronormorphinone. It is soluble in ethanol. The 14-hydroxydihydronormorphinone was suspended in 200 cc of pure ethylalcohol, half its weight of sodium bicarbonate and half its weight of allylbromide added and the resulting mixture was refluxed at about 75°C for 48hours. The solution was cooled, e.g., to 10°C and filtered and the alcoholremoved under a vacuum of 30 mm. The residue was dissolved in chloroformand filtered. The chloroform was removed under a vacuum of 30 mm and theresidue was crystallized from ethylacetate. The crystallized product, N-allyl-1,4-hydroxydihydronormorphinone, has a melting point of 184°C, is soluble inchloroform and insoluble in petroleum ether. The yield amounts to 20% basedon the weight of the reacted 14-hydroxydihydromorphinone. |
| Brand name | Narcan (Bristol-Myers Squibb); Narcan (Endo). |
| Therapeutic Function | Narcotic antagonist |
| Biological Functions | Because of its fast onset (minutes), naloxone (Narcan)administered IV is used most frequently for the reversalof opioid overdose. However, it fails to block someside effects of the opioids that are mediated by the δ-receptor, such as hallucinations. The rapid offset ofnaloxone makes it necessary to administer the drug repeatedlyuntil the opioid agonist has cleared the systemto prevent relapse into overdose. The half-life of naloxonein plasma is 1 hour. It is rapidly metabolized via glucuronidation in the liver and cleared by the kidney.Naloxone given orally has a large first-pass effect, whichreduces its potency significantly. Often an overshootwill follow the administration of naloxone for overdose.The heart rate and blood pressure of the patient mayrise significantly. The overshoot is thought to be due toprecipitation of acute withdrawal signs by naloxone.Given alone to nonaddicts, naloxone produces no pharmacologicaleffects. Naloxone is approved for use in neonates to reverserespiratory depression induced by maternal opioid use.In addition, naloxone has been used to improve circulationin patients in shock, an effect related to blockade ofendogenous opioids. Other experimental and less welldocumented uses for naloxone include reversal of comain alcohol overdose, appetite suppression, and alleviationof dementia from schizophrenia. Side effects ofnaloxone are minor. |
| General Description | Naloxone (Narcan) is a pure antagonist at allopioid receptor subtypes. Structurally, it resembles oxymorphoneexcept that the methyl group on the nitrogen isreplaced by an allyl group. This minor structural change retains high binding affinity to the receptor, but no intrinsicactivity. It is used to reverse the respiratory depressant effectsof opioid overdoses. Naloxone is administered intravenously with an onset ofaction within 2 minutes. Because it is competing with theopioid for the receptor sites, the dose and frequency of administrationwill depend on the amount and type of narcoticbeing antagonized. Overdoses of long-acting opioids(methadone) may require multiple IV doses of naloxone orcontinuous infusions. Neonates born to opioid-exposedmothers may be given IV naloxone at birth to reverse the effectsof opiates. Very few metabolism studies on naloxone have beenconducted, although the major metabolite found in the urineis naloxone-3-glucuronide. |
| Clinical Use | Naloxone has no analgesic activity. The compoundis the standard antidote to treat opioid adversereactions, opioid overdoses, or to stop an intendeduse of an opioid compound. Typical indicationsare inhibition of opioid-induced respiratorydepression, termination of opioid anesthesiaor protection of neonates following opioidtreatment during labor. Naloxone has a shortduration of action and repetitive administrationmay be necessary to antagonize longer actingagonists. To avoid parenteral misuse of nonscheduledoral opioid formulations (tilidine,pentazcocine), a small amount of naloxone isadded which is orally inactivated, but is fullyactive after parenteral administration. Naloxone is orally inactive and is only usedparenterally in single or repetitive doses of 0.4–2 mg up to a total dose of 10 mg, as an intravenousbolus injection or by infusion. The compoundis more potent against pure opioid agoniststhan against mixed agonist – antagonists.Caution should be used in opioid-dependent personsor in persons under high-dose opioid treatment,as naloxone may precipitate an acute withdrawalreaction. Naloxone is relatively free ofside effects. Nausea, vomiting, and convulsionshave occasionally been reported. |
| Synthesis | Naloxone, (-)-17-(allyl)-4,5-epoxy-3,14-dihydroxymorphinan-6-one (3.1.92),is synthesized by the alkylation of 14-hydroxydihydronormorphinane (3.1.82) by allylbromide [55¨C58]. |
Naloxone Preparation Products And Raw materials
| Raw materials | Cyanogen bromide-->OXYMORPHONE-->Allyl bromide-->Hydrochloric acid-->Acetic anhydride-->(5alpha)-6,7,8,14-tetradehydro-4,5-epoxy-6-methoxy-17-methylmorphinan-3-ol-->Morphinan-6-one, 3-(acetyloxy)-4,5-epoxy-14-hydroxy-17-methyl-, (5α)--->6,11b-Ethano-7H-furo[2',3',4',5':4,5]phenanthro[9,8a-d]oxazol-11(11aH)-one, 2-(acetyloxy)-5,5a,9,10-tetrahydro-, (5aR,6R,8aS,11aR,11bS)--->Morphinan-3,14-diol, 4,5-epoxy-6,6-dimethoxy-17-(2-propen-1-yl)-, (5α)--->IDDUCSVQXOGMNE-GVVUEQADSA-N-->Naloxone hydrochloride-->14-hydroxymorphine-6-one |
| Preparation Products | Naltrexone 3-Methyl Ether-->7,8-Dihydro-14-hydroxy- normorphinone |
