23277-43-2

Basic information

• Product Name: NALBUPHINE HYDROCHLORIDE
• Synonyms: NalbuphineHCl;17-(Cyclobutylmethyl)-4,5-epoxymorphinan-3,6,14-triol hydrate hydrochloride;Nalbuphine hydrate hydrochloride;Nalbuphine hydrochloride hydrate,17-(Cyclobutylmethyl)-4,5-epoxymorphinan-3,6,14-triol hydrochloride hydrate;17-(Cyclobutylmethyl)-4,5-epoxymorphinan-3,6,14-triol hydrochloride hydrate;Nalbuphine hydrochloride solution;17-cyclobutylmethyl-4,5-alpha-epoxymorphinan-3,6-alpha,14-triolhydrochloride;6-alpha)-lph
• CAS NO: 23277-43-2
• Molecular Formula: C₂₁H₂₇NO₄*ClH
• Molecular Weight: 393.9
• EINECS: 245-549-9
• Mol File: 23277-43-2.mol
• Article Data: 3

Chemical Properties

• Boiling Point: 566.6 °C at 760 mmHg
• Flash Point: 9℃
• Appearance: White to almost white Solid. (crystal(s); crystalline powder)
• Vapor Pressure: 1.12E-13mmHg at 25°C
• Storage Temp.: ?20°C
• Solubility: H2O: soluble
• CAS DataBase Reference: NALBUPHINE HYDROCHLORIDE(CAS DataBase Reference)
• NIST Chemistry Reference: NALBUPHINE HYDROCHLORIDE(23277-43-2)
• EPA Substance Registry System: NALBUPHINE HYDROCHLORIDE(23277-43-2)

Safety Data

• Hazard Codes: T+,T,F
• Statements: 26/27/28-39/23/24/25-23/24/25-11
• Safety Statements: 22-36/37/39-45-36/37-16
• RIDADR: 1544
• WGK Germany: 3
• RTECS: QD3181000
• HazardClass: 6.1(a)
• PackingGroup: II
• Hazardous Substances Data: 23277-43-2(Hazardous Substances Data)

Usage

Description

Nalbuphine Hydrochloride is a pharmaceutical compound that serves as the hydrochloride salt form of Nalbuphine, a mixed opioid agonist-antagonist. It is primarily known for its analgesic properties, providing relief from moderate to severe pain. As an opioid ligand, it has the ability to bind to opioid receptors in the central nervous system, offering a unique balance of pain relief with a lower risk of respiratory depression and addiction compared to full agonist opioids.

Uses

Used in Pharmaceutical Industry:
Nalbuphine Hydrochloride is used as an analgesic for the management of moderate to severe pain. Its application is particularly beneficial due to its mixed agonist-antagonist properties, which provide effective pain relief while reducing the risk of respiratory depression and addiction associated with full agonist opioids.
Used in Research and Development:
Nalbuphine Hydrochloride is used as an opioid ligand in research and development for the study of opioid receptor interactions and the development of new pain management therapies. Its unique pharmacological profile makes it a valuable tool for understanding the mechanisms of opioid action and for designing novel drugs with improved safety and efficacy profiles.

Therapeutic Function

Analgesic

Acquired resistance

Nalbuphine is an antagonist at μ receptors and an agonist at κ receptors. As an antagonist, it has approximately one-fourth the potency of naloxone, and it produces withdrawal when given to addicts. On a weight basis, the analgesic potency of nalbuphine approaches that of morphine. An intramuscular injection of 10 mg will give about the same degree and duration of analgesia as an equivalent dose of morphine.

Clinical Use

Nalbuphine is only available for parenteral dosage. Its elimination half-life is 2 to 3 hours. Metabolism of nalbuphine is by conjugation of the 3-OH group, and greater than 90% of the drug is excreted as conjugates in the feces.

Side effects

Side effects of nalbuphine are like those of other κ. Dysphoria is not as common as with pentazocine. Sedation is the most common side effect. Nalbuphine does not have the adverse cardiovascular properties found with pentazocine and butorphanol. Nalbuphine has low abuse potential and is not listed under the Controlled Substances Act.

InChI:InChI=1/C21H27NO4.ClH/c23-14-5-4-13-10-16-21(25)7-6-15(24)19-20(21,17(13)18(14)26-19)8-9-22(16)11-12-2-1-3-12;/h4-5,12,15-16,19,23-25H,1-3,6-11H2;1H/t15-,16+,19-,20-,21+;/m0./s1

Upstream product

• 52446-24-9 (-)-4,5α-epoxy-3,14-dihydroxymorphinan-6-one hydrochloride 
• 33522-95-1 noroxymorphone 
• 16676-33-8 (4R,4aS,7aR,12bS)-3-(cyclobutylmethyl)-4a,9-dihydroxy-2,3,4,4a,5,6-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline-7(7aH)-one 
• 20594-83-6 nalbuphine 

Downstream Products

• 20594-83-6 nalbuphine 
• 1056881-16-3 3-O-MEM-6-O-TrO-PEG₅-nalbuphine 
• 1056881-15-2 3-O-MEM-6-O-TrO-PEG₄-nalbuphine 

Relevant articles and documents

One-Pot Process for Synthesis of Nalbuphine Hydrochloride and Impurity Control Strategy

An improved kilogram-scale process of synthesis of nalbuphine was developed by investigating the critical parameters. Ten process-related impurities were identified, of which the source and control strategy was elucidated. Moreover, tetramethylammonium triacetoxyborohydride (Me4NBH(OAc)3) was developed to reduce the imine and ketone in one pot. As a result, 6-β-epimer was significantly controlled to only 0.08% in the crude nalbuphine. The improved process was robust at kilogram scale in 60.4% overall yield with 99.95% high-performance liquid chromatography (HPLC) purity.

Dealkylation of opioid ethers

An improved process for the dealkylation of alkyl aryl ethers to aryl phenols is provided. In this process, an alkyl aryl ether, such as a methyl ether of an opioid, is contacted with an aqueous acid selected from HBr, HCl, or HI which contains at least one equivalent weight, based on the ether, of boric acid or an inorganic salt of a metal selected from Li, Na, K, Al, Mg, Ca, Mn and Ni. MgBr2 in aqueous HBr is preferred in dealkylating an N-substituted 14-hydroxydihydronorcodeine.