BARBITURIC ACID, a white, crystalline, organic chemical compound prepared by condensing di-ethyl malonate and urea, is soluble in water, alcohol and ether. It forms salts (q.v.) with metals and these metal salts may be reacted with organic halogen compounds to form other compounds in which either one or two, as desired, of the hydrogen atoms of the orig inal barbituric acid have been replaced by an organic radical. These same substituted compounds may be prepared directly by using a substituted derivative of di-ethyl malonate in the original condensation. Barbituric acid finds little use except as a starting material for the preparation of derivatives. Barbitone is spar ingly soluble in cold water while sodium barbitone is very soluble. The dose of either is 3 to 10 grains. These two drugs are quickly absorbed and act rapidly. Within an hour or so of the adminis tration by mouth of a therapeutic dose drowsiness is induced, and a satisfactory period of natural sleep should ensue. The effect lasts from six to twelve hours and no unpleasant after-effects should follow the taking of a single clinical dose.
Many other derivatives of barbituric acid have been introduced: Luminal or diphenyl barbituric acid and its sodium salt "Sodium luminal," dose II to 5 grains. These drugs have also been used for warding off the convulsions of epilepsy and are given in doses of - to 1 grain once or twice daily for this purpose; Proponal or dipropyl barbituric acid, dose 2 to 6 grains as hypnotic; Soneryl or butyl-ethyl barbituric acid, dose 1 to 3 grains; Dial or di-allyl barbituric acid, dose I to 4i grains; Gardenal or phenyl ethyl barbituric acid ; Plsanodrom or cyclo hexenyl barbituric acid.
Combinations of barbituric acid with other compounds are : Allonal, a combination of allyl isopropyl barbituric acid with amidopyrin; Veramon, a combination of veronal and ethyl amido phenyl di-methyl pyrazolon; Cibalgin, a combination of dial and amidopyrin; Beatol, a combination of veronal with extracts of valerian and jusquiame ; Somni f ene, a mixture of veronal and allyl isopropyl barbituric acid.
The barbituric acid derivatives are powerful drugs, and it is most important that they should be taken only under medical advice. If these drugs are taken in doses exceeding the proper therapeutic dose poisonous effects may follow ; thus, instead of sleep, deep loss of consciousness or coma may result. In this condition there is great danger of bronchopneumonia (so called veronal pneumonia) which is a complication usually having a fatal termination.
The continued daily use of full therapeutic doses of barbituric acid compounds may be followed by symptoms of chronic poison ing such as headache, vertigo, severe mental depression and moral changes. The speech may become thick and articulation indistinct ; the gait ataxic and reeling like that of alcoholic intoxi cation or cerebellar disease. Cerebral symptoms, such as drowsi ness, visual hallucinations, delusions, squint, double vision, facial weakness, ptosis and nystagmus may occur. Skin rashes have been observed. Abnormal conditions of the urine such as the presence of albumen and casts have been described.
Drug Addiction (q.v.) may follow the continued daily thera peutic use of the barbituric acid group of drugs, and this is fre quently accompanied by some of the symptoms above described.
The mental depression associated with persons addicted to the frequent use of barbituric acid compounds sometimes leads to the taking of a large overdose with fatal result. The returns of the registrar-general for England and Wales show from 1905 to 1925 a total of 257 cases of fatal poisoning from barbituric acid deriva tives, most of these being cases of barbitone poisoning.
"Tolerance" to the barbituric acid group of drugs does not fol low their continued use. It is therefore of great importance that the therapeutic dose should never be exceeded. In this respect these drugs differ from other addiction drugs, such as morphine and cocaine, where a remarkable tolerance may be established. Fatal Dose.—In a healthy adult about 5o grains of barbitone probably represents the average minimum fatal dose. Cases of death have been recorded after taking much smaller doses, but in these other factors were usually present so that death was probably not entirely due to the drugs.
Regulations as to Sale.—On April 14, 1914, the barbituric acid group of drugs were placed under Part II. of the Schedule of Poisons. In 1918 they were placed under Part I. of the Poisons Schedule by order of the Privy Council. (W. H. WI.) BARBIZON, a village, near the forest of Fontainebleau, France, which gave its name to the "Barbizon school" of painters, whose leaders were Corot, Rousseau, Millet and Daubigny, to gether with Diaz, Dupre, Jacque, Francais, Harpignies and others. They put aside the conventional idea of "subject" in their pic tures of landscape and peasant life, and went direct to the fields and woods for their inspiration. The distinctive note of the school is seen in the work of Rousseau and of Millet, each of whom, after spending his early years in Paris, made his home in Barbizon. Unappreciated, poor and neglected, it was not until after years of struggle that they attained recognition and success. They both died at Barbizon—Rousseau in 1867 and Millet in 1875. It is difficult now to realize that their work, so unaffected and beautiful, sliould have been so hardly received. To understand this, it is necessary to remember the conflicts that existed between the classic and romantic schools in the first half of the 19th century, when the classicists, followers of the tradition of David, were the predominant school. The romantic movement, with Gericault, Bonington and Delacroix, was gaining favour. In 1824 Constable's pictures were shown in the Salon, and confirmed the younger men in their resolution to abandon the lifeless pedantry of the schools and to seek inspiration from nature. In those troubled times Rousseau and Millet unburdened their souls to their friends, and their published lives contain many letters, some extracts from which will express the ideals which these artists held in common, and show clearly the true and firmly-based foundation on which their art stands. Rousseau wrote, "It is good composition when the objects represented are not there solely as they are, but when they contain under a natural appearance the sentiments which they have stirred in our souls. . . . For God's sake, and in rec ompense for the life He has given us, let us try in our works to make the manifestation of life our first thought : let us make a man breathe, a tree really vegetate." And Millet—"I try not to have things look as if chance had brought them together, but as if they had a necessary bond between themselves. I want the people I represent to look as if they really belonged to their sta tion, so that imagination cannot conceive of their ever being any thing else. People and things should always be there with an object. I want to put strongly and completely all that is necessary, for I think things weakly said might as well not be said at all, for they are, as it were, deflowered and spoiled—but I profess the greatest horror for uselessness (however brilliant) and filling up. These things can only weaken a picture by distracting the attention toward secondary things." In another letter he says—"Art began to decline from the moment that the artist did not lean directly and naively upon impressions made by nature. Cleverness natur ally and rapidly took the place of nature, and decadence then began. . . . At bottom it always comes to this: a man must be moved himself in order to move others, and all that is done from theory, however clever, can never attain this end, for it is im possible that it should have the breath of life." The ideas of the "Barbizon school" only gradually obtained acceptance, but its chief members now rank among the greater artists of their time.