Nelson R. Trenner

Combined clinical and metabolic study of the effects of alpha-methyldopa on hypertensive patients.

The urinary metabolites of orally administered 2-14C-labeled α-methyldopa were measured in 20 hypertensive patients before and after treatment with α-methyldopa in a dose of 3.0 g daily for 3 months. There was considerable variation in the absorption, biotransformation and excretion of α-methyldopa after an oral dose, but differences in clinical response to α-methyldopa could not be attributed to this.Approximately 40% of the urinary excretion products of α-methyldopa was recovered as unchanged methyldopa, 31% as α-methyldopa-O-sulfate, 8% as 3-methoxy-α-methyldopa, 9% as neutral fraction, 3% as free base, and 3% as conjugated base.The percentage of 3-methoxy-α-methyldopa was increased following prolonged treatment with α-methyldopa, suggesting induction of catechol-O-methyl transferase. The percentage of 3-methoxy-α-methyldopa at the final study was correlated with reductions in standing blood pressure, but not with supine blood pressure. No other changes in the metabolism of α-methyldopa could be attributed to chronic administration of the drug, and no correlation was found between the excretion patterns of the other urinary metabolites of α-methyldopa and hypotensive effect. Tolerance to the hypotensive effect of α-methyldopa occurred in four patients, but in another four an increasing hypotensive effect was seen. The development of tolerance to the hypotensive action of α-methyldopa could not be explained on a metabolic basis.The inhibition of decarboxylation of tyrosine to tyramine and of tryptophan to tryptamine was studied at the initiation of therapy and again after chronic treatment with α-methyldopa. In the majority of patients, inhibition of decarboxylase was markedly increased after chronic treatment, especially when tryptophan was the substrate. In four patients, tolerance to the inhibition of decarboxylation of tyrosine, but not of tryptophan, occurred, and in three of these patients a good hypotensive effect was maintained. There was no correlation between the inhibition of decarboxylase and reduction of blood pressure.

A General Infrared Spectrophotometric Technique for the Determination of Deuterium in Organic Compounds

useful when titrating a basic material which may pick up CO2 from the air, or when titrating a compound which is very susceptible to oxidation. The flask is kept in a constant temperature bath because pK values may be temperature dependent. In practice a known amount of acid or base is added with a pipet and the pH is read and the spectrum scanned as soon as equilibrium is obtained. The pumping action provides sufficient stirring, and a steady state is reached in one or two minutes. After the spectral region desired has been scanned, the spectrophotometer is reversed to return to the starting wavelength and another portion of acid or base is added. The stirring is sufficient by the time the spectrophotometer is ready to scan the region again.

Gas-liquid radiochromatography or 14C-containing compounds with combustion and collection of the resulting [14C]carbon dioxide in hyamine

Abstract A new approach is reported for the gas-liquid radiochromatography of 14C-containing compounds. The column effluent is split between a mass detector and a combustion system, and the [14C]carbon dioxide arising from the individual chromatographic components is trapped in vials containing Hyamine. Each vial is then subjected to conventional radioassay by liquid scintillation counting. Applications of this approach to biosynthesis and drug metabolism problems are presented.

Coenzyme Q. XLIII. The new 5-chloromethyl-6-chromanyl acetate of vitamin K1(20)

Abstract A new and unexpected 6-chromanyl derivative of vitamin K 1(20) has been isolated from an acetylated enzymic reaction mixture obtained after incubating vitamin K 1(20) in a light-inactivated, cell-free extract of Mycobacterium phlei . The structure of the new compound was established as the 5-chloromethyl-6-chromanyl acetate derivative I of vitamin K 1(20) ; its non-enzymic origin was confirmed later by chemical transformations of vitamin K 1(20) .