It may be used alone or as an adjunct to other therapy giving the possibility of increasedtherapeutic effect with little risk of interaction.
In some markets, the drug is supplied as an over-the-counter cream (Lonol in Mexico fromBoehringer Ingelheim) used for topical treatment of musculoskeletal system disorders: sprains, strains, bursitis, tendinitis, synovitis, myalgia, periarthritis.
Benzydamine has been used recreationally. If taken in excess amounts, it acts as adeliriant andCNS stimulant.[6] Such use, particularly among teenagers, has been reported in Brazil,[7][8] Poland,[6] Romania, and Turkey.[citation needed]
Benzydamine is well tolerated. Occasionally oral tissue numbness or stinging sensations may occur, as well as itching, a skin rash, skin swelling or redness, difficulty breathing and wheezing.
It selectively binds to inflamed tissues (Prostaglandin synthetase inhibitor) and is normally free of adverse systemic effects.Unlike other NSAIDs, it does not inhibit cyclooxygenase or lipooxygenase, and is not ulcerogenic.[6][9]
Synthesis starts with the reaction of theN-benzyl derivative frommethyl anthranilate withnitrous acid to give theN-nitroso derivative. Reduction by means ofsodium thiosulfate leads to the transient hydrazine (3), which undergoes spontaneous internal hydrazide formation. Treatment of the enolate of this amide with 3-chloro-1-dimethylamino propane gives benzydamine (5). Please note there is an error in this section: US3318905 states that the nitroso derivative is reduced with sodium hydrosulfite (sodium dithionite) and not with sodium hyposulfite (sodium thiosulfate), as shown in the above scheme and stated in text.
An interesting alternative synthesis of this substance starts by sequential reaction ofN-benzylaniline withphosgene, and then withsodium azide to produce the corresponding carbonyl azide. On heating, nitrogen is evolved and a separatable mixture ofnitrene insertion product and the desired ketoindazole # results. The latter reaction appears to be aCurtius rearrangement type product to produce an N-isocyanate #, which then cyclizes. Alkylation of the enol with sodium methoxide and 3-dimethylaminopropyl chloride gives benzydamine.
Alternatively, use ofchloroacetamide in the alkylation step followed by acid hydrolysis producesbendazac instead.
It also has somecannabinoid activity in rats but has not been tested in humans.[10] It is also hypothesized to act on5-HT2A receptors due to its structural similarity withserotonin.[5]
^Turnbull RS (February 1995). "Benzydamine Hydrochloride (Tantum) in the management of oral inflammatory conditions".Journal.61 (2):127–34.PMID7600413.
^Müller-Peddinghaus R (May 1987). "New pharmacologic and biochemical findings on the mechanism of action of the non-steroidal antiphlogistic, benzydamine. A synopsis".Arzneimittel-Forschung (in German).37 (5A):635–45.PMID3304305.
^Maamer M, Aurousseau M, Colau JC (1987). "Concentration of benzydamine in vaginal mucosa following local application: an experimental and clinical study".International Journal of Tissue Reactions.9 (2):135–45.PMID3610512.
^abPalazzo G, Corsi G, Baiocchi L, Silvestrini B (January 1966). "Synthesis and pharmacological properties of 1-substituted 3-dimethylaminoalkoxy-1H-indazoles".Journal of Medicinal Chemistry.9 (1):38–41.doi:10.1021/jm00319a009.PMID5958958.
^Baiocchi L, Corsi G, Palazzo G (1965). "Ricerche nel campo degli indazoli.—Nota 1. Sulla ciclizzazione termica di azidi di acidi N-aril-N-benzil-carbamici".Annali di Chimica.55:116–25.
^Fanaki NH, el-Nakeeb MA (December 1992). "Antimicrobial activity of benzydamine, a non-steroid anti-inflammatory agent".Journal of Chemotherapy.4 (6):347–52.doi:10.1080/1120009X.1992.11739190.PMID1287137.
^Fanaki NH, El-Nakeeb MA (March 1996). "Antibacterial activity of benzydamine and antibiotic-benzydamine combinations against multifold resistant clinical isolates".Arzneimittel-Forschung.46 (3):320–3.PMID8901158.
