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Cinchocaine Base Powder Suppliers and Factory in China - Local Anesthetic Drug CAS 73-78-9
Definition
ChEBI: A monocarboxylic acid amide that is the 2-(diethylamino)ethyl amide of 2-butoxyquinoline-4-carboxylic acid. One of the most potent and toxic of the long-acting local anesthetics, its parenteral use was restricted to spinal anesthesia. It is now generally only used (usually as the hydrochloride) in creams and ointments and in suppositories for temporary relief of pain and itching associated with skin and anorectal conditions.
Manufacturing Process
A benzene solution of 2.2 parts of α-chloro-γ-quinoline-carboxylic acid chloride is gradually mixed, while cooling, with 2.3 parts of unsymmetrical diethylethylenediamine. When the reaction is at an end the solution is washed with water and the new base extracted by means of hydrochloric acid. The base is precipitated by means of sodium carbonate and extracted with benzene. The solvent is distilled and the base recrystallized from petroleum ether. The α-chloro-γ-quinoline-carboxylic acid diethyl-amino-ethylene amide forms colorless lamina crystals of melting point 74°C. With acids the base forms neutral salts soluble in water.
A solution of 2.5 parts of sodium in n-butylalcohol is boiled with 30 parts of α- chloro-γ-quinoline-carboxylic acid diethyl-amino-ethylene-amide in a reflux apparatus, and when the reaction is over the excess of butylalcohol is distilled. The remaining base is taken up with ether; the solution is washed with water and dried. The solvent is then distilled. The α-n-butoxy-γ-quinoline. carboxylic acid diethyl-amino-ethylene-amide forms as colorless crystals, after recrystallization from petroleum ether melting point of it 64°C.
In practice it is usually used as hydrochloride.
General Description
Articaine has a secondary nitrogen with a pKa of 7.8. It contains an aromatic thiophene ring bioisostere of the phenyl ring found in most other amide anesthetics. The log P of a benzene ring is 2.13 and the thiophene ring log P is 1.81, thus the thiophene ring is more hydrophilic than a phenyl ring. Although the thiophene ring has less lipid solubility than a phenyl ring, articaine is a lipid-soluble compound due to the propylamine, the branched methyl and the substitutions on the thiophene ring. The onset of action of articaine is similar to lidocaine’s onset of action.
Tips: hcl soluble in water, base insoluble in water. (Some Base dissolves in hot water!)
Clinical Use
Articaine is available in a 4% solution with epinephrine for use in infiltration and nerve block anesthesia. Articaine is metabolized rapidly via plasma and tissue carboxyesterase to its primary metabolite, the inactive, water-soluble carboxylic acid. Approximately 40% to 70% of articaine administered epidurally is metabolized to the carboxylic acid, articainic acid. Approximately 4% to 15% of the articainic acid undergoes glucuronide conjugation and only 3% of the dose is recovered unchanged in the urine. The rapid plasma metabolism and reported inactivity of the carboxylic acid metabolite make articaine a potentially safer anesthetic agent when multiple or large doses are necessary.
Uses
Cinchocaine is a local anesthetic, used for Na+ channel blocker.
Anesthesia Strength Note
Local anesthesia strength: the anesthesia effect of some base is stronger than hcl
Tetracaine > Lidocaine > Benzocaine > Procaine
Details
Frequently Asked Questions
Q
What is Cinchocaine and what are its primary clinical applications?
Cinchocaine is a monocarboxylic acid amide and a potent, long-acting local anesthetic that functions as a Na+ channel blocker. While its parenteral use was previously restricted to spinal anesthesia due to its high toxicity, it is now primarily used in creams, ointments, and suppositories for the temporary relief of pain and itching associated with skin and anorectal conditions.
Q
How is the hydrochloric acid salt of Cinchocaine prepared in practice?
It is synthesized by reacting a benzene solution of α-chloro-γ-quinoline-carboxylic acid chloride with unsymmetrical diethylethylenediamine under cooling. The resulting base is washed, extracted using hydrochloric acid, precipitated with sodium carbonate, and recrystallized. This intermediate is further reacted with sodium in n-butylalcohol to yield the final base, which is commonly converted into its hydrochloride salt form for practical use.
Q
Why is Articaine lipid-soluble despite having a hydrophilic thiophene ring?
Although the thiophene ring in Articaine has a lower log P (1.81) compared to a benzene ring (2.13), making it more hydrophilic, the overall molecule remains lipid-soluble. This lipid solubility is attributed to the presence of the propylamine group, the branched methyl group, and specific substitutions on the thiophene ring.
Q
How is Articaine metabolized and excreted by the body?
Articaine is rapidly metabolized via plasma and tissue carboxyesterases into its inactive, water-soluble primary metabolite, articainic acid. Approximately 40% to 70% of epidurally administered articaine is converted to this metabolite. About 4% to 15% of articainic acid undergoes glucuronide conjugation, and only 3% of the active dose is recovered unchanged in the urine.
Q
What is the order of local anesthesia strength among the common anesthetics mentioned?
Based on the comparative strength of local anesthesia, the order is Tetracaine > Lidocaine > Benzocaine > Procaine. Additionally, the anesthetic effect of some base forms is stronger than their corresponding hydrochloride (HCl) salts.