Benzonatate Chemical Properties

Boiling point:

649.0±55.0 °C(Predicted)

Density 

1.096±0.06 g/cm3(Predicted)

storage temp. 

Refrigerator, under inert atmosphere

solubility 

Chloroform (Slightly), Methanol (Slightly)

pka

2.20±0.39(Predicted)

form 

Oil

color 

Light Yellow to Light Brown

BCS Class

3?

CAS DataBase Reference

104-31-4(CAS DataBase Reference)

Safety Information

Hazardous Substances Data

104-31-4(Hazardous Substances Data)

Toxicity

LD50 oral in mouse: 400mg/kg

Benzonatate Usage And Synthesis

Description

Benzonatate is a reversible voltage-gated sodium channel blocker. It blocks Na_v1.7 currents in a concentration- and voltage-dependent manner (IC₅₀s = 5.9 and 1.4 μM at holding potentials of -100 and -70 mV, respectively) and inhibits action potential firing in catecholamine A differentiated (CAD) cells. Benzonatate also blocks 80% of Na_v1.3 currents in N1E-115 cells when used at a concentration of 100 μM. In vivo, benzonatate (0.85 mg/min) reduces the frequency, but has no effect on the amplitude, of the cough reflex in anesthetized dogs. Formulations containing benzonatate have been used as antitussive agents for the treatment of coughs.

Originator

Tessalon,Endo (Du Pont),US,1958

Uses

Antitussive

Definition

ChEBI: The ester obtained by formal condensation of 4-butylaminobenzoic acid with nonaethylene glycol monomethyl ether. Structurally related to procaine and benzocaine, it has an anaesthetic effect on the stretch sensors in the lungs, and is used as a non-narcoti cough suppressant.

Manufacturing Process

4.42 parts of para-butylamino-benzoic acid ethyl ester are put with 16.0 parts of a mixture of polyethylene glycol monomethyl ethers, boiling at 180°-220°C at a pressure of 0.01 mm of mercury, in a closed reaction vessel which is fitted with an adjustable inlet tube for solvents and a connection for distilling off in vacuo. In order to dry the mixture completely, it is heated for an hour at 100°-105°C and absolute xylene is introduced under the surface of the mixture in vacuo at a pressure of 12 mm of mercury. There is thus a constant stream of xylene steam passing through the whole apparatus, which removes the last traces of moisture and any other volatile impurities. The xylene is condensed in a cooler. The whole is cooled to 20°-30°C and 0.06 part of sodium methylate dissolved in 0.6 part of methanol is added.
Thereupon xylene is introduced again in vacuo at a temperature of 100°- 105°C whereby all the methanol and the ethanol formed during reesterification evaporates. The re-esterification is continued under these conditions until a specimen of the reaction mass is clearly soluble in cold water, which occurs after about 2-3 hours. There is now obtained in almost quantitative yield the ester of the formula wherein n stands for approximately 7 to 9, which still contains an excess of polyethylene glycol monomethyl ether. The ester is purified by dissolving in benzene and being washed several times with a sodium carbonate solution of 5% strength. It is advantageous to agitate all the washing solutions with fresh benzene. In this distribution between benzene and sodium carbonate solution the new ester remains in the benzene, the excess polyethylene glycol monomethyl ether and a small amount of brown impurities are taken up by the dilute soda solution. By evaporating the dried and filtered benzene solution there is obtained the new ester in the form of a colorless to very faintly yellow oil which is easily soluble in most organic solvents with the exception of aliphatic hydrocarbons. The new ester is precipitated from aqueous solutions when heated to about 42°C. but it dissolves again readily on cooling.

brand name

Tessalon (Forest).

Therapeutic Function

Antitussive

Biological Functions

Benzonatate (TessaIon) is related to the local anesthetic tetracaine. It anesthetizes the stretch receptors in the lungs, thereby reducing coughing.Adverse reactions include hypersensitivity, sedation, dizziness, and nausea.

Mechanism of action

It is believed that it acts by two mechanisms: selective anesthesia of irritated receptors in the lungs and simultaneous suppression of the cough center.

Synthesis

Benzonatate, p-butylaminobenzoate 2,5,8,11,14,17,20,23,26-nonaoctacozan- 28-ol (23.2.2), is synthesized by reesterifying the ethyl ester of 4-butylaminobenzoic acid with the monomethyl ether nonaethylenglycol. It is a structural analog of the local anesthetic tetracaine.

Benzonatate(104-31-4)Related Product Information

• Diphenyl carbonate
• Benzyl butyl phthalate
• 4-Aminobenzoic acid
• Triphenyl phosphite
• Triphenyl phosphate
• Benzyl benzoate
• m-Anisidine
• 2-Methoxyethanol
• p-Anisidine
• Dimethyl isophthalate
• Polyethylene Glycol Monomethyl Ether
• Dimethyl phthalate
• Methyl anthranilate
• Benzocaine
• o-Anisidine
• Diphenyl chlorophosphate
• Anthranilic acid
• PENTAETHYLENE GLYCOL