357-08-4 Usage
Uses
Used in Pharmaceutical Industry:
Naloxone hydrochloride is used as a specific opioid antagonist for reversing the effects of opioids in cases of overdose or during surgery.
Used in Narcotic Antidote:
Naloxone hydrochloride is used as a narcotic antagonist to counteract the effects of narcotics, particularly in emergency situations involving opioid overdose.
Used in Opioid Addiction Treatment:
Naloxone hydrochloride is used in combination with buprenorphine for the treatment of opiate addiction, helping to manage pain and prevent relapse.
Used in Pain Management:
Naloxone hydrochloride is used as a nonspecific opiate receptor antagonist that displays antinociceptive effects, aiding in pain management.
Used in Research and Forensic Applications:
Naloxone hydrochloride is utilized in research and forensic applications due to its specific opioid antagonist properties, allowing for the study and analysis of opioid effects and overdose cases.
Brand names for Naloxone hydrochloride include Narcan (Bristol-Myers Squibb) and Narcan (Endo).
Originator
Narcan,Du Pont,US,1971
Manufacturing Process
10 grams of 14-hydroxydihydromorphinone (oxymorphone) was converted
into its diacetate by warming it on the steam bath with 80 cc of acetic
anhydride for about 2 hours. The acetic anhydride was removed on the water
bath under a vacuum of about 30 mm absolute pressure. The melting point of
the residue was 220°C. The residue was taken up in 100 cc of chloroform. An
equal amount by weight of cyanogen bromide was added and the mixture was
refluxed at about 60°C for about 5 hours. After refluxing, the mixture was
washed with 100 cc of a 5% aqueous hydrochloric acid solution, dried over
sodium sulfate and the chloroform removed by evaporation under a vacuum of
about 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 with
300 cc of 20% aqueous hydrochloric acid solution, and treated with a small
amount, e.g., 1 gram of charcoal. The hydrochloric acid was then removed
under a vacuum of 15 mm, the residue dissolved in 30 cc of water and
precipitated by the addition of 2.4 cc of concentrated aqueous ammonia. The
precipitate 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 ethyl
alcohol, half its weight of sodium bicarbonate and half its weight of allyl
bromide added and the resulting mixture was refluxed at about 75°C for 48
hours. The solution was cooled, e.g., to 10°C and filtered and the alcohol
removed under a vacuum of 30 mm. The residue was dissolved in chloroform
and filtered. The chloroform was removed under a vacuum of 30 mm and the
residue was crystallized from ethylacetate. The crystallized product, N-allyl-
1,4-hydroxydihydronormorphinone, has a melting point of 184°C, is soluble in
chloroform and insoluble in petroleum ether. The yield amounts to 20% based
on the weight of the reacted 14-hydroxydihydromorphinone.
Therapeutic Function
Narcotic antagonist
Clinical Use
#N/A
Veterinary Drugs and Treatments
Naloxone is used in veterinary medicine almost exclusively for its
opiate reversal effects, but the drug is being investigated for treating
other conditions (e.g., septic, hypovolemic or cardiogenic
shock). Naloxone may also be employed as a test drug to see if
endogenous opiate blockade will result in diminished tail chasing
or other self-mutilating behaviors. It, potentially, could be useful
for treating overdoses of clonidine or the CNS effects of benzodiazepines
(ivermectin?), but more research is necessary before recommending
its use.
Drug interactions
Potentially hazardous interactions with other drugs
None known
Metabolism
Naloxone hydrochloride is rapidly metabolised in the
liver, mainly by conjugation with glucuronic acid to
naloxone-3-glucuronide, which is excreted in the urine
References
1) Le Bourdonnec?et al., (2008),?Novel trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidines as mu opioid receptor antagonists with improved opioid receptor selectivity profiles: Bioorg. Med. Chem. Lett..?18?2006
2) Boyer?et al.?(2012),?Management of opioid analgesic overdose; New Engl. J. Med.?367?146
3) Wang?et al.?(2017),?Opioids and opioid receptors orchestrate wound repair;?Transl. Res.?185?13
4) Wright and Rodgers (2013),?Low dose naloxone attenuates the pruritic but not anorectic response to rimonabant in male rats; Psychopharmacology (Berl.)?226?415
Check Digit Verification of cas no
The CAS Registry Mumber 357-08-4 includes 6 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 3 digits, 3,5 and 7 respectively; the second part has 2 digits, 0 and 8 respectively.
Calculate Digit Verification of CAS Registry Number 357-08:
(5*3)+(4*5)+(3*7)+(2*0)+(1*8)=64
64 % 10 = 4
So 357-08-4 is a valid CAS Registry Number.
InChI:InChI=1/C19H21NO4.ClH/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;1H/t14-,17+,18+,19-;/m1./s1
357-08-4Relevant articles and documents
Caged Naloxone: Synthesis, Characterization, and Stability of 3- O -(4,5-Dimethoxy-2-nitrophenyl)carboxymethyl Naloxone (CNV-NLX)
Lewin, Anita H.,Fix, Scott E.,Zhong, Desong,Mayer, Louise D.,Burgess, Jason P.,Mascarella, S. Wayne,Reddy, P. Anantha,Seltzman, Herbert H.,Carroll, F. Ivy
, p. 563 - 567 (2018/03/27)
The photolabile analogue of the broad-spectrum opioid antagonist naloxone, 3-O-(4,5-dimethoxy-2-nitrophenyl)carboxymethyl naloxone (also referred to as "caged naloxone", 3-O-(α-carboxy-6-nitroveratryl)naloxone, CNV-NLX), has been found to be a valuable biochemical probe. While the synthesis of CNV-NLX is simple, its characterization is complicated by the fact that it is produced as a mixture of αR,5R,9R,13S,14S and αS,5R,9R,13S,14S diastereomers. Using long-range and heteronuclear NMR correlations, the 1H NMR and 13C NMR resonances of both diastereomers have been fully assigned, confirming the structures. Monitoring of solutions of CNV-NLX in saline buffer, in methanol, and in DMSO has shown CNV-NLX to be stable for over a week under fluorescent laboratory lights at room temperature. Exposure of such solutions to λ 365 nm from a hand-held UV lamp led to the formation of naloxone and CNV-related breakdown products.
Method for synthesis of naloxone hydrochloride
-
Paragraph 0103-0110, (2017/03/22)
The invention belongs to the technical field of medicament synthesis, and relates to a synthetic method of naloxone hydrochloride. The method comprises the following steps: by adopting thebaine as a starting material, oxidizing and then reducing thebaine to obtain a compound 2, reacting the compound 2 with acetic anhydride to obtain an ester compound 3, then removing methyl and performing hydrolysis to obtain a compound 4, reacting the compound 4 with an alkylating reagent (such as the reagent selected from chloropropene, bromopropene, iodopropylene or the combination thereof), performing allylation on the Nth bit of a mother nucleus structure to obtain a compound 5, then removing methyl to obtain naloxone free alkali, then forming acid addition salts with hydrochloric acid, and then refining to obtain naloxone hydrochloride which can be used as a medicinal raw material medicament. By adopting the method disclosed by the invention, a high-quality medicinal raw material medicament can be prepared.
Pharmaceutical combinations of oxycodone and naloxone
-
, (2008/06/13)
Disclosed in certain embodiments is a pharmaceutical composition comprising from 10 to 40 mg of oxycodone or a pharmaceutically acceptable salt thereof and 0.65 to 0.90 mg naloxone or a pharmaceutically acceptable salt thereof.
Process for the preparation of morphinane derivatives
-
, (2008/06/13)
The invention relates to a process for the preparation of morphinane derivatives of general formula: STR1 by demethylation of 3-methoxylated compound with a sulfonic acid selected from methanesulfonic acid and trifluoromethanesulfonic acid in the presence of a sulfide.
