5-ALLYL-5-[1-METHYLBUTYL]-2-THIOBARBITURIC ACID

Absorption

Rapidly absorbed (high lipid solubility).

Toxicity

Intravenous LD50 in rat is 51 mg/kg.

Description

Thiamylal, 5-allyl-5-(1- methylbutyl)-2-thiobarbituric acid, The sodium salt , Mr 276.36, is an amorphous powder soluble in water. It is prepared by condensation of thiourea with a malonic ester , .

Originator

Surital,Parke Davis,US,1951

The Uses of 5-ALLYL-5-[1-METHYLBUTYL]-2-THIOBARBITURIC ACID

Thiamylal is a barbiturate derivative with sedative, anticonvulsant and hypnotic effects. Thiamylal is used for induction in surgical anaesthesia as well as an anticonvulsant to counteract side effects from other anaesthetics. Thiamylal is a Controlled Substance.

Indications

Used for the production of complete anaesthesia of short duration, for the induction of general anaesthesia, and for inducing a hypnotic state.

Background

A barbiturate that is administered intravenously for the production of complete anesthesia of short duration, for the induction of general anesthesia, or for inducing a hypnotic state. (From Martindale, The Extra Pharmacopoeia, 30th ed, p919)

Definition

ChEBI: A member of the class of barbiturates that is 2-thioxodihydropyrimidine-4,6(1H,5H)-dione substituted by a pentan-2-yl and prop-2-en-1-yl group at position 5.

Manufacturing Process

In 450 cc of methanol is added 47 grams of sodium metal and the mixture allowed to completely react to form a methanol solution of sodium methoxide. The methanol solution of sodium methoxide is then cooled to 60°C and 68 grams of thiourea which has been thoroughly dried is added with stirring until a uniform solution is formed. Thereafter, 157 grams of diethyl allyl-(1- methylbutyl)malonate is added to the solution of the sodio derivative of thiourea at a temperature of 55°C and the condensation reaction mixture maintained at the said temperature for 24 hours. Methyl alcohol is removed under vacuum during the course of the reaction while maintaining a temperature of 55°C.
The viscous reaction mixture is then poured into 1.5 liters of ice water and agitated to form a uniform solution. The solution is treated with activated carbon and filtered. Thereafter, 80% acetic acid is added until the filtered solution remains acidic to litmus. The precipitate formed is filtered and washed thoroughly with distilled water. The product is air-dried at a temperature of 95° to 100°C for 48 hours to yield 133 grams of 5-allyl-5-(1- methylbutyl)-2-thiobarbituric acid having a melting point of 132° to 133°C and assaying at 99.5% pure, from US Patent 2,876,225.

Therapeutic Function

Anesthetic

Pharmacokinetics

Thiamylal, a barbiturate, is used in combination with acetaminophen or aspirin and caffeine for its sedative and relaxant effects in the treatment of tension headaches, migraines, and pain. Barbiturates act as nonselective depressants of the central nervous system (CNS), capable of producing all levels of CNS mood alteration from excitation to mild sedation, hypnosis, and deep coma. In sufficiently high therapeutic doses, barbiturates induce anesthesia.

Metabolism

Hepatic.