Chemical Properties
White or light-yellow, waxy solid. Very slightly soluble in water; soluble in
alcohol, ether, benzene, chloroform.
Definition
ChEBI: A benzoate ester in which 4-N-butylbenzoic acid and 2-(dimethylamino)ethanol have combined to form the ester bond; a local ester anaesthetic (ester caine) used for surface and spinal anaesthesia.
Biological Functions
Tetracaine hydrochloride (Pontocaine) is an ester of
PABA that is an effective topical local anesthetic agent and also is quite commonly used for spinal (subarachnoid)
anesthesia. Epinephrine is frequently added to
prolong the anesthesia.Tetracaine is considerably more
potent and more toxic than procaine and cocaine. It
has approximately a 5-minute onset and 2 to 3 hours of
action.
General Description
Tetracaine was developed to address the low potency andshort duration of action of procaine and chloroprocaine. The addition of the butyl side chain on the para nitrogen increasesthe lipid solubility of the drug and enhances the topical potencyof tetracaine. The plasma half-life is 120 to 150 seconds.Topically applied tetracaine to unbroken skin requires 30 to 45minutes to confer topical anesthesia. Tetracaine 4% gel is superiorthan eutectic mixture with lidocaine (EMLA) (an emulsionof lidocaine and prilocaine) in preventing pain associatedwith needle procedures in children. Tetracaine metabolism issimilar to procaine ester metabolism yielding parabutylaminobenzoicacid and dimethylaminoethanol and conjugatesexcreted in the urine. The pKa of the dimethylated nitrogen is8.4 and tetracaine is formulated as a hydrochloride salt with apH of 3.5 to 6.0. The increased absorption from topical siteshas resulted in reported toxicity. Overdoses of tetracaine mayproduce central nervous system (CNS) toxicity and seizure activitywith fatalities from circulatory depression reported.No selective cardiac toxicity is seen with tetracaine althoughhypotension has been reported. Tetracaine is employed for infiltrationanesthesia, spinal anesthesia, or topical use.
Biochem/physiol Actions
Tetracaine also refers as 4-(Butylamino)benzoic acid 2-(dimethylamino)ethyl ester interfere with calcium movement in muscle and non-muscle cells and can inhibit potassium-induced as well as caffeine-induced shortening of outer hair cells (OHC′s). But, the product can′t inhibit electrically-induced shortening of OHC′s.The product can also stimulate caspase activation and inhibits pro-survival signalling pathways which in turn induce human renal cell apoptosis.
Synthesis
General procedure for the synthesis of 2-(dimethylamino)ethyl 4-(butylamino)benzoate from bromobutane and 2-(dimethylamino)ethyl 4-aminobenzoate: 5.0 g of p-aminobenzoic acid-2-dimethylaminoethyl ester (0.024 mol), 3.3 g of 1-bromonobutane (0.024 mol), 10.0 g of K2CO3 (0.072 mol) and 50 mL of N,N-dimethylformamide were added to a 100 mL three-neck flask. ) and 50 mL of N,N-dimethylformamide were added to a 100 mL three-neck flask. The mixture was stirred and heated to 50 °C, keeping the reaction temperature at 50 °C. After 5 hours of reaction, the heating was stopped and the reaction system was allowed to cool to room temperature. The reaction mixture was filtered and the filtrate was extracted with 50 mL of dichloromethane. The aqueous phase was extracted again with 50 mL of dichloromethane. The organic phases were combined and 5.3 g of white solid product was obtained in 82.8% yield after evaporating the solvent.
Veterinary Drugs and Treatments
Tetracaine is more irritating than proparacaine but is sometimes
used in veterinary medicine. It is indicated to produce local anesthesia
of short duration for ophthalmic procedures including measurement
of intraocular pressure (tonometry), removal of foreign
bodies and sutures, and conjunctival and corneal scraping in diagnosis
and gonioscopy. Tetracaine is also indicated to produce local
anesthesia prior to surgical procedures in humans such as cataract
extraction and pterygium excision, usually as an adjunct to locally
injected anesthetics. Ophthalmic solutions used for intraocular
procedures should be preservative-free. Preservatives may cause
damage to the corneal epithelium if a significant quantity of solution
enters the eye through the incision.
References
[1] Patent: CN106518697, 2017, A. Location in patent: Paragraph 0014
[2] Patent: US1889645, 1932,
[3] Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 19, p. 1536
