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Biomedical subjects

W D Paton

Publications and source records attributed to W D Paton.

At least 55 records · Page 3Linked to original sources

Use of trimethylsilyl and other homologous trialkylsilyl derivatives for the separation and characterization of mono- and dihydroxycannabinoids by combined gas chromatography and mass spectrometry.

A gas chromatographic separation of dihydroxy- from monohydroxycannabinoids by the use of homologous trialkylsilyl derivatives is discussed. Trimethylsilyl derivatives produced a group of peaks containing both sets of compounds, sometimes poorly resolved, whereas by increasing the alkyl chain length to n-butyl complete fractionation into two groups, was achieved. The mass spectra of these derivatives resembled those of the trimethylsilyl derivatives with the addition of a set of ions resulting from estimation of the Si-alkyl chains as olefins.

Acetamides↗

The control of the plasma choline concentration in the cat.

1. Changes in choline concentration of the blood after injections or infusions of choline were studied in cats anaesthetized with chloralose.2. Single I.V. injections of choline 10-100 mumole/kg produced arterial plasma levels 1 min later corresponding to an apparent volume of initial distribution of 430 ml./kg. The concentration then declined rapidly (half-time, 1-2 min), with a later slower decline after large doses.3. Infusions of choline at a rate of 0.8 mumole/kg.min or greater produced steady rises in plasma level, corresponding to a clearance of 28.6 ml. plasma/kg.min. The half time of rate of approach to steady state was 7 min or less. Infusions at rates of 0.40 mumole/kg.min or less produced much smaller or negligible rises, suggesting mechanisms for disposal which were saturated at higher concentration. At low rates, little infused choline appeared in urine. At the end of an infusion, the plasma choline level usually fell without delay.4. Portal blood contained about 50% of the arterial level, renal venous blood 15-70%, caval blood 30-60%, and amniotic fluid 2.5%. Occlusion of renal coeliac or mesenteric arteries raised plasma choline, but relatively rapid choline removal still occurred in the eviscerate animal.5. After infusions of [methyl-(14)C]choline, the level of radioactivity retained in the circulation amounted to only a few per cent of the total dose infused. At low rates of infusion (0.0125-0.1 mumole/kg.min) the radioactivity represented only a small fraction of bio-assayable choline; but at 0.40 mumole/kg.min it came to exceed the concentration of free choline, indicating metabolic conversion. Only traces of (14)C were found in expired air, and only 1-1.5% of total infused radioactivity in the urine. After infusion of 150 mumole over 3 hr, high levels of radioactivity were found in liver, kidney, lung, brain and heart, but levels in muscle and spleen were comparable to that of blood.6. It was concluded that choline is rapidly lost from the blood, that the abdominal viscera, liver, kidney and lung are important extraction sites, that some partial metabolism occurs, the metabolites also being rapidly lost from blood, and that it is probable that choline lost to the tissues becomes bound in some form.

Animals↗

Effect of cannabis and certain of its constituents on pentobarbitone sleeping time and phenazone metabolism.

1. Cannabis extract prolonged sleeping time in mice in a thermally neutral environment (30-32 degrees C) in which hypothermia does not occur. The prolongation was dose related, just detectable at 50 mg/kg, and 4-fold at 500 mg/kg.2. Under these conditions, ether sleeping time was not prolonged.3. Cannabis extract inhibited the aerobic metabolism of phenazone by a microsome-rich 9,000 g supernatant of mouse liver homogenate capable of nicotinamide adenine dinucleotide phosphate (NADPH) generation.4. Delta(1)-Tetrahydrocannabinol (Delta(1)-THC) prolonged pentobarbitone sleep and inhibited phenazone metabolism, but its action was limited, and could not account for the effect of the extract. The carotenes and water-soluble fractions of the extract were inactive on pentobarbitone sleep.5. Cannabidiol was strongly active by both tests; in vivo 39.8 muM/kg (12.5 mg/kg) prolonged sleep by 190%, and in vitro 12.7 muM inhibited phenazone metabolism 20%. These actions were dose related, and could account for the effect of the extract.6. The prolongation of pentobarbitone sleep by cannabis extract in a dose of 200 mg/kg, intraperitoneally, was maximal when given 30 min before the pentobarbitone, still present at 3 h, but undetectable at 24 hours. No phase of enhanced metabolism at 24 or 48 h after single cannabis injection was detected.7. It is concluded that cannabis extract inhibits microsomal activity of mouse liver, chiefly by virtue of its cannabidiol content. It is probable that cannabis consumption by man could lead to altered disposal of many other drugs, used in medicine or otherwise.

Aerobiosis↗