General
Preferred name
BENZYDAMINE
Synonyms
BENZYDAMINE HYDROCHLORIDE ()
1-Propanamine, n,n-dimethyl-3-((1-(phenylmethyl)-1h-indazol-3-yl)oxy)- ()
Benzydamine HCl ()
AF864 ()
Benzydamine (hydrochloride) ()
benzydamine flufenamate ()
Difflam-P ()
Benzidamine hydrochloride ()
Difflam ()
Tantum ()
NSC-759276 ()
AF-864 ()
Lozamine ()
Apo-benzydamine ()
Benzindamine ()
Benzydamine-d6 (hydrochloride) ()
P&D ID
PD009138
CAS
132-69-4
642-72-8
1246817-20-8
Tags
natural product
drug
available
Drug Status
approved
withdrawn
Drug indication
Antipyretic
Analgesic
Anti-Inflammatory
Chemotherapy or radiotherapy-induced mucositis
Max Phase
Phase 4
Probe control
Probe control not defined
Orthogonal probes
0
No orthogonal probes found
Similar probes
0
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
PHARMACODYNAMICS
Benzydamine is a non-steroidal anti-inflammatory drug (NSAID) designed to elicit local anesthetic and analgesic effects mainly for the mouth and throat. It specifically acts on the local mechanisms of inflammation such as pain, oedema, or granuloma. Typically applied topically, the drug demonstrates anti-inflammatory activity reducing oedema as well as exudate and granuloma formation. Moreover, benzydamine exhibits analgesic properties and local anaesthetic activity if pain is caused by an inflammatory condition. Benzydamine can be absorbed into the oral mucosa and intact skin. Once absorbed in the local area of pain or inflammation, benzydamine binds selectively to local inflamed tissues, usually allowing it to act with few adverse systemic effects. On average a period of 2 to 4 hours is necessary for the substance to reach peak plasma concentration. [L1120]; ; Benzydamine can be synthesized with the reaction of the N-benzyl derivative from methyl anthranilate with nitrous acid to give N-nitoso derivative. This is next reduced by sodium thiosulfate to give transient hydrazine. This hydrazine can then undergo spontaneous internal hydrazide formation. Treating this resultant enolate with 3-chloro-1-dimethylamkino propane ultimately yields benzydamine.
ROE
The relatively high lipid solubility of the weak base benzydamine is thought to be associated with considerable passive resorption within the renal tubule, which suggests that only approximately 5% of benzydamine is excreted unchanged in the urine [A27273]. At the same time however, other studies have suggested that considerably larger amounts (50-65%) of the drug is excreted unchanged in urine [A31530].; ; While several inactive oxidized metabolites of benzydamine are excreted in urine, the benzydamine N-oxide metabolite can remain in plasma and demonstrate a half-life that is longer than the parent benzydamine compound [A27273].; ; Nevertheless, it is generally believed that excretion occurs mainly through urine and is mostly in the form of inactive metabolites or conjugation products [L2466].
TOXICITY
A possible adverse reaction associated with the use of the mouthwash or oromucosal spray formulations of benzymadine is potential numbness and/or stinging in the mouth and/or throat [L1120, L1121].; ; Some possible adverse reactions that tend to be associated more with topical cream formulations of benzymadine include increased sensitivity to sunlight, and localized itching, skin rash, redness, or swelling [L1123].; ; The prescribing information for all formulations of benzymadine however, warn against the possibility of severe allergic reaction (anaphylaxis) associated with swelling of the throat and mouth, difficulty in swallowing, speaking, and breathing, or wheezing [L1120, L1121, L1123].; ; As benzydamine is a non-steroidal anti-inflammatory drug (NSAID), it is necessary to determine if a patient is allergic to NSAIDs before considering its use [L1120, L1121, L1123].; ; Intoxication is expected as a consequence of accidental ingestion of large quantities of benzydamine (over 300 mg ingestion). Other symptoms associated with overdose of ingested benzydamine include gastrointestinal and central nervous system symptoms like nausea, vomiting, abdominal pain, oesophageal irritation, dizziness, hallucinations, agitation, anxiety, and irritability [L1121].; ; The official prescribing information for benzydamine generally suggest that benzydamine mouthwashes and sprays should not be used in pregnancy [L1121, L1123] . Similarly, the official prescribing information for benzydamine also generally suggest that benzydamine mouthwashes and sprays should not be used during lactation unless considered essential by a physician [L1121, L1123].; ; The prescribing information for topical cream formulations of benzydamine note that benzydamine cream should not be used in pregnancy or lactation unless considered necessary by the physician [L1120].; ; Overall, non-clinical data reveal no special hazards for humans based on conventional studies of safety pharmacology, repeated toxicity, genotoxicity, cardiogenic potential, and toxicity to reproduction [L1120]. Additionally, there is no evidence of teratogenic effects in animal studies [L1121].
METABOLISM
Benzydamine is primarily metabolized by oxidation, dealkylation, and conjugation into hydroxy, dealkylated, and N-oxide metabolites [L1121, A31528].; ; In general, however, when used at the recommended doses the levels at which benzydamine is absorbed or exposed into the body are usually not sufficient to produce systemic pharmacological effects [L
MOA
Despite being categorized as a non-steroidal anti-inflammatory drug (NSAID), benzydamine demonstrates various mechanisms of action that differ from those of traditional aspirin-like NSAIDs. In particular, benzydamine predominantly acts by inhibiting the synthesis of pro inflammatory cytokines like tumour necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β) without largely affecting other pro inflammatory cytokines (ie. such as IL-6 and IL-8) or anti-inflammatory cytokines (ie. like IL-10 or IL-1 receptor antagonist). [A31528, L1120]; ; Moreover, benzydamine is largely a weak inhibitor of prostaglandin synthesis as it has been shown to effectively inhibit cyclooxygenase (COX) and lipoxygenase enzyme activity only at concentrations of 1mM or greater. Considering most contemporary usages of benzydamine are topical applications that are generally not well absorbed through the skin and/or non-specialized mucosae, benzydamine does not often achieve the kind of absorption or blood concentrations necessary to cause any extraneous distant systemic effects or COX inhibition, allowing it to localize its action. [A31528, L1120]; ; Additionally, it is also hypothesized that benzydamine is capable of inhibiting the oxidative burst of neutrophils and membrane stabilization. These actions are exhibited by the substanceâs ability to inhibit the release of granules from neutrophils and to stabilize lysosomes. [A31528, L1120]; ; Furthermore, benzydamine is capable of a local anaesthetic effect that may be related to its capability for inhibiting the release of inflammatory mediators like substance P and calcitonin gene related peptide from sensory nerve endings. Since substance P is capable of causing the release of histamine from mast cells, benzydamineâs prevention of substance P release further contributes to an anti-inflammatory effect. [A31528, L1120]; ; Benzydamine also demonstrates a non-specific antibacterial activity against various bacterial strains that are resistant to broad-spectrum antibiotics such as ampicillin, chloramphenicol, and tetracycline at concentrations of about 3 mmol/L. Combinatorial use of benzydamine and other antibiotics like tetracycline and chloramphenicol are also synergistic against antibiotic resistant strains of *Staphylococcus aureus* and *Pseudomonas aeruginosa*. [A31528]
INDICATION
Available predominantly as a liquid mouthwash, oromucosal spray, or topical cream, benzydamine is most frequently employed as a locally acting analgesic and anti-inflammatory treatment for the relief of painful inflammatory conditions. ; ; When formulated as a mouthwash or spray, benzydamine may be used to treat traumatic conditions like pharyngitis following tonsillectomy or the use of a naso-gastric tube, inflammatory conditions like pharyngitis, aphthous ulcers and oral ulceration due to radiation therapy, dentistry operations and procedures, or more general conditions like sore throat, sore tongue, sore gums, mouth ulcers, or discomfort caused by dentures. [L1121] ; ; When used as a topical cream, benzydamine may be employed to relieve symptoms associated with painful inflammatory conditions of the muscolo-skeletal system including acute inflammatory disorders such as myalgia and bursitis or traumatic conditions like sprains, strains, bruises, sore muscles, stiff joints, or even the after-effects of fractures. [ L1123]
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Cell lines
0
Organisms
1
Compound Sets
18
ChEMBL Approved Drugs
ChEMBL Drugs
Drug Repurposing Hub
DrugBank
DrugBank Approved Drugs
DrugCentral
DrugCentral Approved Drugs
DrugMAP
DrugMatrix
MedChem Express Bioactive Compound Library
NPC Screening Collection
Prestwick Chemical Library
ReFrame library
Selleckchem Bioactive Compound Library
TargetMol Bioactive Compound Library
The Spectrum Collection
Withdrawn 2.0
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
51
Molecular Weight
309.18
Hydrogen Bond Acceptors
4
Hydrogen Bond Donors
0
Rotatable Bonds
7
Ring Count
3
Aromatic Ring Count
3
cLogP
3.42
TPSA
30.29
Fraction CSP3
0.32
Chiral centers
0.0
Largest ring
6.0
QED
0.63
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Pathway
Immunology/Inflammation
Neuroscience
Anti-infection
Target
COX
Bacterial
PGE synthase
Immunology & Inflammation related
Indication
mouth inflammation, throat inflammation
Disease Area
dental, otolaryngology
MOA
prostanoid receptor antagonist
ATC
A01AD02
G02CC03
M01AX07
M02AA05
Toxicity type
opthalmic
Therapeutic Class
Analgesics
Source data
