Physico-Chemical Properties and Hypnotic Action of Substituted Barbituric Acids

Reversal of the Action of Amino Acid Antagonists by Barbiturates and Other Hypnotic Drugs

“…A similar relationship has been described for anaesthetic potency by Butler (1942). However, the relationship can also be observed for the lipid: water partition coefficients (Tabern & Shelberg, 1933 Table 2). None of these latter compounds appeared to have any significant GABA-mimetic action.…”

Depression of Autonomic Ganglia by Barbiturates

“…Ganglion-depressant potencies cannot be related, for example, to oil/water distribution coefficients of the drugs (Tabern and Shelberg, 1933); to rates of hydrolysis of the sodium salts at the pH of the blood (Bush, 1937); to speed of onset of anaesthesia after intravenous administration (Butler, 1942), or to the degree of binding of the drugs to blood proteins (Goldbaum and Smith, 1948 A further possibility is that the variations in ganglion-depressant activity seen after intravenous injection might be influenced by differences in the rate at which the drugs pass from the blood stream into certain body tissues. However, whilst Brodie and his co-workers (1950,1952) have shown that thiopentone is rapidly taken up by the fat depots of the body, thereby accounting for the short duration of action of the drug, they were unable (1953) to demonstrate a similar effect with pentobarbitone-which tends to remain equally distributed throughout the tissues.…”

“…The lack of a definite correlation between ganglionic and central nervous depressant potencies of the various barbiturates is difficult to explain. Ganglion-depressant potencies cannot be related, for example, to oil/water distribution coefficients of the drugs (Tabern and Shelberg, 1933); to rates of hydrolysis of the sodium salts at the pH of the blood (Bush, 1937); to speed of onset of anaesthesia after intravenous administration (Butler, 1942), or to the degree of binding of the drugs to blood proteins (Goldbaum and Smith, 1948). If Butler's figures can be taken as representing the relative rates of fixation of the drugs to nervous tissue, then drugs such as hexobarbitone or thiopentone, which exhibit both short lags and high anaesthetic potencies, might be expected to exhibit high ganglion-depressant potencies.…”

A Rapid Method of Identifying Particular Barbiturate Derivatives in Small Samples of Blood by Paper Chromatography

“…These figures indicate a trend towards higher pK values in the more rapidly running compounds, as would be expected on theoretical grounds, though the fact that amylobarbital and barbital have the same pK value clearly indicates that their wide separation on the chromatogram is due to another factor. Tabern and Shelberg (1933) found that the barbiturate derivatives decreased in water solubility and increased in oil/water distribution coefficient with increase in length of the 5.5 substituted alkyl side-chains, and their data were used by Fuhrman and Field (1943) in reviewing the relationships between the physical properties and physiological actions of a number of barbiturate derivatives. Butler (1950), using mice, showed that the difference in the speed of action of a slowly acting derivative (barbital) and a rapidly acting one (ortal) could be accounted for by the relatively slow appearance of the former substance in brain tissue.…”