Barbituric Acid

BARBITURIC ACID, also called malonylurea, represents a ureide of malonic acid, obtained by heating the latter with urea: " _g/CO-NH\_rn When hydrogens in the malonic acid residue are replaced by alkyls, substances with hypnotic properties are obtained. For the first time, derivatives of malonic acid were introduced into therapy by Fischer (E. Fischer) and Mering (J. Mehring) in 1903 (veronal). The strength of their hypnotic action depends on the corresponding alkyls. Thus, introduction of higher homologs into the molecule increases this action: dimethyl-B. acid generally does not possess it, diethyl-B. acid (see Veronal) possesses it to a high degree, dipropyl-B. acid (propanal) acts approximately 2 times stronger than the previous compound. Replacement of one ethyl group in veronal with a phenyl group (phenyl-ethyl-B. acid - luminal, see) also increases the hypnotic action; however, replacement of both hydrogens in B. acid with aromatic radicals decreases it. Significant hypnotic action belongs to dial (diallyl-B. acid), containing two unsaturated groups in its molecule. According to Alday-Redonnet, dial is 1½ times stronger than luminal and 3½ times stronger than veronal in hypnotic action. In addition to the chemical properties of alkyls, one must consider those changes which they introduce into the physical properties of the hypnotic substance molecule, mainly changes in solubility. Thus, the inactivity of higher homologs can be explained by their very poor solubility and, as a consequence, negligible absorption. Improvement in solubility of B. acid preparations is achieved by obtaining salt-like compounds, for example, C₈H_uNaO₃N₂-veronal-sodium (otherwise medinal). Both veronal-sodium and especially luminal-sodium are used due to their good solubility internally, for subcutaneous injections and in enemas. Preparations of B. acid are used as Hypnotica and as Sedativa. Preparations of B. acid are also used in combination with other Nervina: veronal with codeine-codeonal, with extract of Indian hemp-indonal, with pyramidone-veramon; combination of dial with ethyl-morphine-didial and others. Compounds of B. acid are excreted unchanged in the urine, increasing diuresis, due to their vasodilating action.