Benzydamine and Synthesis

Benzydamine (also known as Tantum Verde, and in some countries as Maxtra Gargle, Difflam, and Septabene), available as the hydrochloride salt, is a topically acting nonsteroidal anti-inflammatory drug (NSAID) with Local anesthetic and analgesic for pain relief and anti-inflammatory – inflammatory treatment for inflammation of the mouth and throat.It belongs to the class of chemicals known as indazoles.

Use 

Medicine

Stomatology: gingivitis, stomatitis, glossitis, aphthous ulcers, mouth ulcers from dental surgery and radiation therapy.Otorhinolaryngology: Glandular fever, pharyngitis, tonsillitis, posttonsillectomy, radiation or intubation mucositis.

It can be used alone or as an adjunct to other therapies, potentially increasing therapeutic effects with little risk of interactions.

In some markets, the drug is available as an over-the-counter ointment (Lonol in Mexico from Boehringer Ingelheim) for topical treatment of disorders of the musculoskeletal system: sprains, strains, bursitis, tendonitis, synovitis, myalgia, Zhou Yan.

Recreational

Benzydamine has been used recreationally.In overdose, it acts as a delirium and central nervous system stimulant.This use, especially in adolescents, has been reported in Brazil,Poland,Romania, and Turkey.

Contraindications

Apart from known hypersensitivity reactions, there are no contraindications to the use of benzodiazepines.

Side effects

Benzydamine was well tolerated.Occasionally, numbness or tingling of mouth tissues occurs, as well as itching, rash, skin swelling or redness, difficulty breathing, and wheezing.

Pharmacology

It binds selectively to inflamed tissues (prostaglandin synthase inhibitor) and generally has no adverse systemic effects.Unlike other NSAIDs, it does not inhibit cyclooxygenase or lipoxygenase and is not ulcerative has a strong reinforcing effect, and has cross-sensitization effects with heroin, cocaine and other drugs of abuse in animals.Presumably, it possesses cannabinoid agonistic activity.

Pharmacokinetics

Benzydamine is poorly absorbed through the skin and vagina.

Synthesis

The synthesis begins with the reaction of the N-benzyl derivative of methyl anthranilate with nitrous acid to give the N-nitroso derivative.Reduction by sodium thiosulfate leads to transient hydrazine which undergoes spontaneous internal hydrazide formation.Treatment of the enolate of this amide with 3-chloro-1-dimethylaminopropane affords the benzylamine.Please note that there is an error in this part:US3318905 states that the nitroso derivatives are reduced with sodium dithionite (sodium dithionite), not sodium dithionite (sodium thiosulfate), as shown in the above scheme and in the text mentioned.Another interesting synthesis of this substance involves the sequential reaction of N-benzylaniline with phosgene and then with sodium azide to give the corresponding carbonyl azide.On heating, nitrogen gas is evolved to form a mixture of the isolatable nitrene insertion product and the desired ketoindazole#. The latter reaction appears to be a Curtius rearrangement-type product, leading to N-isocyanate # followed by cyclization.Alkylation of enols with sodium methoxide and 3-dimethylaminopropyl chloride affords benzylamines.Alternatively, use chloroacetamide instead of benzazac in the alkylation step after acid hydrolysis.