Benzydamine

Structural formula
General
Surname	Benzydamine
other names	1-Benzyl-3- [3- (dimethylamino) propoxy] -1 H -indazole; N , N -dimethyl-3 - {[1- (phenylmethyl) -1 H -indazol-3-yl] oxy} -1-propanamine;
Molecular formula	C 19 H 23 N 3 O; C 19 H 24 ClN 3 O ( hydrochloride );
Brief description	white solid (hydrochloride)
External identifiers / databases
EC number	211-388-8
ECHA InfoCard	100.010.354
PubChem	12555
ChemSpider	12036
DrugBank	DB09084
Wikidata	Q793143
properties
Molar mass	309.41 g · mol -1 ; 345.87 g mol −1 (hydrochloride);
Physical state	firmly
Melting point	160 ° C (hydrochloride)
solubility	soluble in water (hydrochloride)
safety instructions
GHS labeling of hazardous substances Hydrochloride; Caution
H and P phrases	H: 302-319
	P: 305 + 351 + 338
Toxicological data	25 mg kg −1 ( LD 50 , mouse , iv ) ; 460 mg kg −1 ( LD 50 , mouse , oral ) ; 950 mg kg −1 ( LD 50 , rat , oral ) ; 33 mg kg −1 ( LD 50 , mouse , iv , hydrochloride) ; 440 mg kg −1 ( LD 50 , mouse , oral , hydrochloride) ; 43.5 mg kg −1 ( LD 50 , rat , iv , hydrochloride) ; 740 mg kg −1 ( LD 50 , rat , oral , hydrochloride) ;
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Benzydamine (trade names: neo-angin , Tantum (- Verde , - Rosa ) or Difflam ) is an anti-inflammatory, analgesic and antibacterial agent that is used locally in the form of a gargle solution, spray or lozenge for the symptomatic treatment of pain and irritation in the mouth and mouth Throat area is used, for example for a sore throat. The funds are administered several times a day. Preparations for systemic use (coated tablets, capsules, injection solutions) are no longer available in Germany.

Presentation and extraction

Benzydamine is produced in a three-stage synthesis. In the first step the methyl 2-benzylaminobenzoate is obtained by an N -alkylation of methyl anthranilate using benzyl chloride . The subsequent ring closure is achieved by a reaction with sodium nitrite in a hydrochloric acid medium to form nitrosamine and subsequent reduction with sodium hydrogen sulfite to form the hydrazine derivative (not shown in the formula scheme). The target compound is then obtained by etherification with 3-dimethylaminopropyl chloride in the presence of sodium methylate .

Structure and properties

Benzydamine is found in pharmaceuticals as benzydamine hydrochloride . It is a benzylated indazole - derivative .

Effects

Benzydamine (A01AD02) has anti-inflammatory, local anesthetic, mildly bactericidal and fungicidal properties. Taken orally, it is also antipyretic and pain reliever and is also known as a non-steroidal anti-inflammatory.

Indications

For the symptomatic treatment of pain and irritation in the mouth and throat, for example a sore throat.

dosage

According to the specialist information. The drugs are used several times a day. Eating, drinking, or maintaining oral hygiene can reduce its effectiveness.

Possible unwanted effects

Possible unwanted effects include photosensitivity (sensitivity to light, increased risk of sunburn), hypersensitivity reactions such as itching, burning, dry mouth, glottis cramps and angioedema (swelling of the skin and mucous membranes).

Pharmacological properties

Pharmacodynamic properties

Benzydamine is an indolic non-steroidal anti-inflammatory drug (NSAI) for local therapy as a gargle solution, lozenge / lozenge or as a spray. Benzydamine is lipophilic at pH 7.2, shows membrane affinity and has a membrane-stabilizing effect with a local anesthetic effect. In contrast to other NSAIs, benzydamine does not inhibit either cyclooxygenases or lipoxygenases (10 ⁻⁴ mol / l) and is not ulcerogenic. Both phospholipase A2 and lysophosphatide acyltransferase are slightly inhibited (> 10 ⁻⁴ mol / l). PGE2 synthesis in macrophages is stimulated at 10 ⁻⁴ mol / l. The formation of reactive oxygen species from phagocytes is markedly inhibited in the concentration range 10 ⁻⁵ to 10 ⁻⁴ mol / l . Phagocyte degranulation and aggregation are inhibited at 10 ⁻⁴ mol / l. The strongest in vitro effects occur when leukocyte adhesion to the vascular endothelium is inhibited (3 to 4 times 10 ⁻⁶ mol / l). Benzydamine has antithrombotic properties in the rat (ED 35 8.5 mg / kg po) and reduces the mortality induced by the platelet-activating factor (PAF) in the mouse (50 mg / kg po; p <0.05). It is concluded that benzydamine has an anti-inflammatory effect by preventing vascular lesions by activated, adherent and emigrating leukocytes , ie it is vasoprotective. The pronounced local anesthetic effect contributes to rapid pain relief. Benzydamine inhibits the permeability of the capillaries and thus has an anti-edematous effect. These properties are complemented by the antiseptic effect. Benzydamine is well tolerated and causes a targeted local therapy of the inflammation symptoms and swallowing difficulties without causing any noteworthy systemic effects.

Pharmacokinetic properties

Absorption

When applied locally, the active ingredient penetrates very well through the skin and mucous membrane surfaces and accumulates in the underlying inflammatory tissue. Resorption through the mucous membrane of the mouth and throat is demonstrated by a measurable amount of benzydamine in human blood serum. Approximately two hours after using a 3 mg lozenge, the maximum plasma concentration of benzydamine is 37.8 ng / ml, the AUC reaches a value of 367 ng / ml * h. However, these values are not sufficient to achieve systemic pharmacological effects.

distribution

When administered orally, benzydamine is extensively and slowly distributed into the tissues ( distribution volume = 100 l). The binding to plasma proteins is only 10 to 15%.

Biotransformation

Around 40% of a single dose is excreted in the urine in the form of polar metabolites (mainly benzydamine N -oxide and 5-hydroxybenzydamine glucuronide) and 5% as unchanged benzydamine. 70% of the administered dose is eliminated via the kidneys.

elimination

The plasma half-life is about ten hours.

Web links

Entry on Benzydamine in Flexikon , a Wiki of the DocCheck company

Entry on Benzydamine in the Pharmawiki

Individual evidence

↑ ^a ^b ^c Entry on Benzydamine at TCI Europe, accessed on April 12, 2016.
↑ ^a ^b ^c data sheet Benzydamine hydrochloride, analytical standard from Sigma-Aldrich , accessed on April 11, 2016 ( PDF ).
↑ ^a ^b ^c ^d ^e ^f ^g ^h A. Kleemann , J. Engel, B. Kutscher, D. Reichert: Pharmaceutical Substances - Synthesis, Patents, Applications , 4th edition (2001) Thieme-Verlag Stuttgart, ISBN 978-1- 58890-031-9 .
↑ RS Turnbull: Benzydamine Hydrochloride (Tantum) in the management of oral inflammatory conditions. In: Journal (Canadian Dental Association). Volume 61, Number 2, February 1995, pp. 127-134, PMID 7600413 (Review).

[TCI-1] Entry on Benzydamine at TCI Europe, accessed on April 12, 2016.

[Sigma-2] ta sheet Benzydamine hydrochloride, analytical standard from Sigma-Aldrich , accessed on April 11, 2016 ( PDF ).

[Kleemann-3] ↑ ^a ^b ^c ^d ^e ^f ^g ^h A. Kleemann , J. Engel, B. Kutscher, D. Reichert: Pharmaceutical Substances - Synthesis, Patents, Applications , 4th edition (2001) Thieme-Verlag Stuttgart, ISBN 978-1- 58890-031-9 .

[4] RS Turnbull: Benzydamine Hydrochloride (Tantum) in the management of oral inflammatory conditions. In: Journal (Canadian Dental Association). Volume 61, Number 2, February 1995, pp. 127-134, PMID 7600413 (Review).