MEPHOBARBITAL

Chemical Properties

White Crystalline Solid

Originator

Isonal, Roussel

Uses

Controlled substance (depressant). Anticonvulsant; sedative; hypnotic

Definition

ChEBI: A member of the class of barbiturates, the structure of which is that of barbituric acid substituted at N-1 by a methyl group and at C-5 by ethyl and phenyl groups.

Manufacturing Process

46 parts metallic sodium was dissolved in 1000 parts absolute alcohol. The obtained solution was mixed with 264 parts of phenyl ethyl malonic acid diethyl ester and 80 parts of monomethyl urea and heated for 8 hours at reflux. Alcohol was distilled off, the residue was dissolved in water and neutralized with diluted sulfuric acid. N-Methylethylphenylbarbituric acid precipitated as a powder. It was filtered off, washed to neutral and dissolved in 50 parts of boiling alcohol. On cooling the obtained methylphenobarbital precipitated as the colorless prisms. MP: 176.5°C. This compound may be also prepared by condensation of equivalents of phenyl malonic ester and monomethyl urea, which was dissolved in above described solution of sodium ethylate.

brand name

Mebaral (Sterling Winthrop); Menta-Bal (Marion Merrell Dow).

Therapeutic Function

Anticonvulsant

General Description

Mephobarbital, 3-methyl-5-ethyl-5-phenylbarbituric acid (metharbital), is metabolicallyN-demethylated to phenobarbital, which many consider toaccount for almost all of the activity. Its principal use is asan anticonvulsant.

Clinical Use

Mephobarbital is a barbiturate-derivative AED with a pKa of 7.7 (log P = 1.84 at pH 7.4). Approximately 50% of an oral dose of mephobarbital is absorbed from the gastrointestinal tract. The plasma concentrations required for its therapeutic effects are unknown. The principal route of mephobarbital metabolism is N-demethylation by the liver to form phenobarbital, which may be excreted in the urine unchanged and as its p-hydroxy metabolite and glucuronide or sulfate conjugates. Conversion to the 4-hydroxy metabolite is stereoselective, being catalyzed by either CYP2C19 (R-enantiomer) or CYP2B6 (S-enantiomer); individuals who are CYP2C19 poor metabolizers show decreased clearance. Approximately 75% of a single oral dose of mephobarbital is converted to phenobarbital. It has not been determined whether mephobarbital contributes to the antiseizure effect or whether it results from its active metabolite, phenobarbital. Similarly, it is unclear whether mephobarbital, like phenobarbital, is a potent inducer of the enzymes involved in the metabolism of other drugs, but because the drug is chemically and pharmacologically similar to phenobarbital and is metabolized to phenobarbital, this possibility is likely.
Mephobarbital is less commonly used in the treatment of generalized and partial seizures. Like phenobarbital, it is classified as a long-acting barbiturate. No evidence exists that it is more effective than phenobarbital in equivalent doses; however, it may be less sedating in children.

Safety Profile

Poison by ingestion and intraperitoneal routes. A human teratogen by an unspecified route with developmental abnormalities of the cardovascular (circulatory) system. When heated to decomposition it emits toxic NOx. See also BARBITURATES.