Benzydamine

Benzydamine

Systematic (IUPAC) name
3-(1-benzyl-1H-indazol-3-yloxy)-N,N-dimethylpropan-1-amine
Clinical data
AHFS/Drugs.com	International Drug Names
Pregnancy category	AU: B2
Legal status	OTC(UK)
Routes of administration	Oral, topical
Pharmacokinetic data
Protein binding	<20%
Biological half-life	13 hours
Excretion	Renal
Identifiers
CAS Number	642-72-8 Y
ATC code	A01AD02 (WHO) G02CC03 M01AX07 M02AA05
PubChem	CID: 12555
ChemSpider	12036 Y
UNII	4O21U048EF Y
KEGG	D07516 Y
ChEMBL	CHEMBL12610 Y
Chemical data
Formula	C19H23N3O
Molecular mass	309.405 g/mol
SMILES n2c(OCCCN(C)C)c1ccccc1n2Cc3ccccc3
InChI InChI=1S/C19H23N3O/c1-21(2)13-8-14-23-19-17-11-6-7-12-18(17)22(20-19)15-16-9-4-3-5-10-16/h3-7,9-12H,8,13-15H2,1-2H3 Y Key:CNBGNNVCVSKAQZ-UHFFFAOYSA-N Y
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Benzydamine (also known as Tantum Verde and branded in some countries as Difflam), available as the hydrochloride, is a locally-acting nonsteroidal anti-inflammatory drug with local anaesthetic and analgesic properties for pain relief and anti-inflammatory treatment of inflammatory conditions of the mouth and throat.

Medical use

• Odontostomatology: gingivitis, stomatitis, glossitis, aphthous ulcers, dental surgery and oral ulceration due to radiation therapy.

• Otorhinolaryngology: pharyngitis, tonsillitis, post-tonsillectomy, radiation or intubation mucositis.

It may be used alone or as an adjunct to other therapy giving the possibility of increased therapeutic effect with little risk of interaction.

In some markets, the drug is supplied as an over-the-counter cream (Lonol in Mexico from Boehringer Ingelheim) used for topical treatment of musculoskeletal system disorders: sprains, strains, bursitis, tendinitis, synovitis, myalgia, periarthritis.

Antimicrobial activity

Studies indicate that benzydamine has notable in vitro antibacterial activity and also shows synergism in combination with other antibiotics, especially tetracyclines, against antibiotic-resistant strains of Staphylococcus aureus and Pseudomonas aeruginosa.

Contraindications

There are no contraindications to the use of benzydamine except for known hypersensitivity.

Side effects

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.

Pharmacology

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.

Recreational use

Benzydamine has been used recreationally. In overdosages it acts a deliriant and CNS stimulant. Such use, particularly among teenagers, has been reported in Poland, Brazil and Romania.

Synthesis

Benzydamine synthesis:

Synthesis starts with the reaction of the N-benzyl derivative from methyl anthranilate with nitrous acid to give the N-nitroso derivative. Reduction by means of sodium thiosulfate leads to the transient hydrazine (3), which undergoes spontaneous internal hydrazide formation. Treatment of the enolate of this amide with 3-chloro-1-dimethylamkino propane gives benzydamine (5).

An interesting alternative synthesis of this substance starts by sequential reaction of N-benzylaniline with phosgene, and then with sodium azide to product the corresponding carbonyl azide. On heating, nitrogen is evolved and a separatable mixture of nitrene insertion product and the desired ketoindazole # results. The latter reaction appears to be a Curtius 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 of chloroacetamide in the alkylation step followed by acid hydrolysis produces bendazac instead.

See also

• AB-FUBINACA
• Pravadoline
• GW-405,833