Ann E. Robinson

The distribution of methadone in man

The distribution of methadone and its metabolite, 1,5‐dimethyl‐3,3‐diphenyl‐2‐ethylidene pyrrolidine, in man, postmortem, is presented. Quantitative data for methadone and the metabolite in blood, bile, urine, liver, kidney, spleen, lung and brain samples show that methadone blood concentrations range from 0·22–3·04 μg/ml and are less than in bile and urine. The metabolite is found particularly in bile and urine. The liver and kidney concentrations are approximately equivalent unless the survival time is reduced by the presence of another CNS‐depressant drug. Lung tissue is the richest source of methadone and brain the poorest. Chromatographic data for three other methadone metabolites are included.

Metabolism of chlorpromazine in humans

Abstract The isolation and characterisation of chlorpromazine metabolites from the urine of psychiatric patients is described. It is shown that chlorpromazine and its mono-and di-demethlated derivatives are hydroxylated and that these hydroxy compounds are conjugated mainly with glucuronic acid and, to a lesser extent, with sulphate. The predominant metabolite was isolated and identified as a monoglucuronide of N-desdimethyl chlorpromazine.

Biotransformations in vitro undergone by phenothiazine derivatives in a liver preparation

Characterisation of the products of biotransformations resulting when a wide range of medicinally used phenothiazine derivatives were incubated with a “microsomal and soluble” fraction of livers from albino Wistar rats, is described. The compounds were chlorpromazine, demethylchlorpromazine, dedimethylchlorpromazine, triflupromazine, promazine, acepromazine, propiomazine, diethazine, promethazine, isopromethazine, ethopropazine, trimeprazine, methotrimeprazine, ethylmemazine, proquamezine, cyamemazine, trifluoperazine, prochlorperazine, thioproperazine, fluphenazine, pecazine, and also the sulphoxides of the first three compounds and of promazine. The predominant reactions were those of dealkylation and of hydroxylation of the aromatic ring. Sulphoxidation did not occur to a significant extent with any of the compounds examined.

The distribution of chloroquine in man after fatal poisoning.

Detailed analysis of autopsy specimens from two fatal cases of chloroquine poisoning is reported. Post‐mortem blood levels of 1.60 and 1.24 mg chloroquine/100 ml blood were found; results for liver blood, urine, stomach contents, liver, lungs and kidneys are given. The highest chloroquine concentration was in liver and the presence of a metabolite was demonstrated in the tissues.

Some factors involved in multiple spot formation in the paper chromatography of sympathomimetic amines in the presence of acids.

The paper chromatographic behaviour of a variety of amines both alone and in the presence of acids in acidic, neutral and basic running solvents is reported. Using a n‐butanol: acetic acid: water solvent, multiple spot formation by several pure sympathomimetic amines was observed in the presence of the stronger organic acids. Many weaker acids affected the amines in a neutral solvent. The results emphasise the need for correct controls and the cautious interpretation of chromatograms of biological extracts since the number of spots produced is not necessarily indicative of the number of bases present.

The Interaction of Phenolic Compounds with Bacteria. Part I. Hexylresorcinol and Escherichia Coli.

Various quantitative aspects of the interaction of hexylresorcinol with E. coli suspensions are described. The amounts of hexylresorcinol bound by the bacteria from solutions of varying concentrations were determined and the speed of this reaction and the influence of temperature on the extent of binding examined. The release of cellular constituents from the bacteria and the changes in the light‐scattering properties of E. coli suspensions on addition of hexylresorcinol were also investigated. These results are discussed in relation to the site of antibacterial action of hexylresorcinol.

THE INTERACTION OF CHELATING AGENTS WITH BACTERIA

The interaction of solutions containing oxine or iron or both (in a 1:1 molar ratio) with Staph, aureus is examined with respect to the chelating agent and metal ion binding by the bacteria. Iron enhances the amount of oxine uptake by the organism although the presence of the chelating agent does not affect the amount of iron bound. Iron is shown to be present in the ferric state in dilute solutions containing oxine. Two types of iron receptor sites in the bacterial surface are postulated and iron is shown to mediate oxine binding by the bacteria.

Toxicology of some autopsy cases involving tricyclic antidepressant drugs.

SummaryThe widespread prescription of antidepressant and tranquilizing drugs has resulted, perhaps inevitably in an increasing incidence of these drugs in specimens from Coroners autopsy cases. Particularly prominent are the tricyclic compounds imipramine and amitriptyline.Examples of toxicological investigations involving these and some other structurally related drugs, nortriptyline, dothiepin and dibenzepin form the basis of this paper.ZusammenfassungDie großzügige Verschreibung der Antidepressiva sowie der Tranquilizer haben zur Vermehrung der Todesfälle geführt. Dabei treten besonders Vergiftungen durch Imipramin und Amitriptyline hervor.In der Arbeit werden Vergiftungen von Imipramin, Nortriptylin, Dothiepin und Dibenzepin beschrieben und die Ergebnisse der chemischen Analysen dargestellt.

The distribution of amylobarbitone, butobarbitone, pentobarbitone and quinalbarbitone and the hydroxylated metabolites in man.

Fluid and tissue specimens collected from 30 subjects at autopsy have been assayed for their content of common sedative barbiturates and the corresponding hydroxylated metabolites by g.l.c. Where one barbiturate had been ingested an inverse relationship between lipid solubility of the drug and the distribution in fluids and tissues was observed. In most cases the liver, and in the remainder the spleen, contained the highest concentrations of barbiturate. Bile concentrations were often in excess of those in the corresponding liver. The metabolites of the four sedative barbiturates were usually present in lower amounts than the parent drugs in the fluids and tissues of most subjects but urine often contained much higher concentrations of metabolites—sometimes exceeding that of the parent drug in the liver. Administration of two or more barbiturates together did not appear to affect the distribution and metabolism of the individual drugs.

The Interaction of Phenolic Compounds with Bacteria. Part II. The Effects of Various Substances on the Interaction of Hexylresorcinol with Escherichia Coli.

The uptake of hexylresorcinol by suspensions of E. coli and the associated release of cellular constituents were examined using heat‐killed and butanol‐treated organisms. The effect of the addition of cetomacrogol to the system was evaluated in terms of the reduction in the extent of drug binding and the prevention of the hexylresorcinol‐dependent light‐scattering changes of E. coli suspensions. Sodium chloride potentiation of the latter effect and of the release of cell exudate from the bacteria on treatment with hexylresorcinol was also investigated.