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Biomedical subjects

A H Beckett

Publications and source records attributed to A H Beckett.

At least 19 recordsLinked to original sources
PubMed1979

Artifacts produced by using dichloromethane in the extraction and storage of some antihistaminic drugs.

The use of dichloromethane for the extraction of amines may lead to the formation of artifacts. Dichloromethane reacts rapidly (37.5 degrees) with brompheniramine, diphenylpyraline, cyclizine, cyproheptadine but not with antazoline and lignocaine. This difference in reactivity as well as the thin-layer chromatographic, gas-liquid chromatographic, nuclear magnetic resonance, and mass spectrometric characteristics of cyclizine and diphenylpyraline chloromethochlorides are investigated.

Chromatography, Gas↗
PubMed1979

Rapid thin-layer chromatographic photodensitometric method for the determination of metoclopramide and clebopride in the presence of some of their metabolic products.

Metoclopramide and its newly developed analogue clebopride, together with some of their metabolic products are quantitated, following extraction from biological tissues and fluids, and subsequent separation on silica gel thin-layer chromatographic plates. Diazotisation, followed by coupling with N-(1-naphthyl)ethylenediammonium dichloride, carried out on the thin-layer plate, is utilised for visualisation. The intensity of the spots is measured by photodensitometric analysis. The effect of variation of various experimental conditions is studied. The method has proven to be satisfactory for the measurement of 20 ng/ml of these compounds in biological material; the results are well within the accepted limits of deviation.

Animals↗
PubMed1979

The N- and alpha- C-oxidation of N,N-dialkylanilines by rabbit liver microsomes in vitro.

1. A method for the determination of N,N-dialkylanilines and their metabolites by g.l.c. is described. 2. N-Demethylation and N-oxidation are important routes of metabolism of N-alkyl-N-methylanilines. 3. N-dealkylation, except the removal of a N-t-butyl group, occurs during the metabolism of N,N-dialkylanilines. 4. N-oxidation was found with N,N-dimethyl and N,N-diethylaniline and all N-methyl-N-alkylanilines examined except N-methyl-N-t-butylaniline. 5. A good correlation was found between the hydrophobic bonding constant (pi) and the extent of demethylation of a series of N-alkyl-N-methylanilines.

Aniline Compounds↗
PubMed1978

Synthesis of 2-aryl-4,4-spiro-morpholinium compounds of possible biologic interest.

The preparation of some 2-hydroxy-2-aryl-4,4-polymethylenemorpholinium bromides (II) by ring closure of the corresponding N-phenacyl-N-hydroxy-ethylpiperidinium (pyrrolidinium) bromide (III) and the synthesis of 2-ethoxy (IV) and of 2,3-dehydro derivatives (VI) are described. The synteshis of 2-phenyl-4,4-pentamethylene-morpholinium bromide (VII) from the hydrogenation of either the 2-phenyl or 2-p-bromophenyl-2,3-dehydromorpholinium derivativies (VI) is also reported. Proof of the chemical structures is provided by IR, UV, and NMR spectroscopy. The synthesized compounds did not present any significant pharmacologic activity.

Animals↗
PubMed1978

Degradation of (--)-ephedrine in solution and during extraction with diethyl ether.

Significant losses occurred during the extraction of small quantities of ephedrine from aqueous media using either regular or analytical grades of diethyl ether. The losses were, at least in part, caused by reaction of the ephedrine with aldehydic impurities in the ether; three substituted oxazolidines were identified, using g.l.c. and g.l.c-ms. These and one other oxazolidine were synthesized and characterized by g.l.c., g.l.c.-ms, nmr and infrared spectroscopy. Alternative mechanisms for ephedrine breakdown were considered. Ephedrine was separately oxidized by three different oxidizing agents and also irradiated by ultraviolet light; the products were characterized by g.l.c., g.l.c.-ms. A method for the purification of diethyl ether is recommended to minimize ephedrine breakdown.

Chemical Phenomena↗
PubMed1978

The disposition of phentermine and its N-oxidized metabolic products in the rabbit.

1. When phentermine was injected intraperitoneally to rabbits, 77% of the dose was excreted in the urine within 2 days; N-oxidized metabolic products accounted for 62% dose. Major excretion products were N-hydroxyphentermine (28% dose), conjugated N-hydroxyphentermine (32% dose) and unchanged phentermine (16% dose). 2. Similarly injected N-hydroxyphentermine was excreted (62% dose) in the urine in 2 days; only 4% dose was recovered unchanged. Major routes of metabolism of N-hydroxyphentermine was conjugation (36% dose) and reduction to the parent amine (15% dose). Conditions for hydrolysis of urine to liberate N-hydroxyphentermine from its conjugates were studied; N-hydroxyphentermide decomposes in strong acid. 3. Only 10% of injected alpha, alpha-dimethyl-alpha-nitroso-beta-phenylethane was excreted in the urine in 2 days. 4. N-Oxidations is the major pathway of metabolism of phentermine in rabbits; the present results suggest that some biological activity may be mediated by the pharmacologically active N-hydroxyphentermine.

Animals↗
PubMed1978

Stereochemistry of the metabolic incorporation of oxygen into (+)- and (-)-N-benzylamphetamine.

1. Both (+)- and (-)-N-benzylamphetamine undergo alpha-carbon and N-oxidation to form N-dealkylated, deaminated and N-oxidized metabolites during incubation with fortified rabbit liver homogenates. 2. Quantitative determination of the metabolites based on specific g.l.c. procedures showed that all activities are localized in the microsomal fraction of rabbit liver. 3. N-Dealkylation, deamination and nitrone and secondary hydroxylamine formation are stereoselective. 4. The characteristics of the enzyme-substrate interactions for both isomers of N-benzylamphetamine indicate that at least two distinct enzyme systems are involved in the N-oxidation and alpha-carbon processes, or a single enzyme possessing an active site with differing conformational requirements for the two oxidative processes.

Amphetamines↗
PubMed1978

The stereoselective metabolism of ethylamphetamine with fortified rabbit liver homogenates.

1. The liver enzyme systems of rabbits involved in the oxidative metabolism of ethylamphetamine were shown to be localized in the microsomal fraction. 2. The effect of substrate concentration, incubation period and storage of the microsomal preparations at 4 degrees was investigated. 3. The results indicate the involvement of at least two stereoselective enzyme systems or different conformations of binding of different substrates to the same enzyme system. R-(-)-Ethylamphetamine is the preferred substrate for N-oxidation and dealkylation, whereas the S-(+)-isomer is preferred for deamination. When racemic ethyl amphetamine is metabolized, the enantiomers act as independent compounds and compete for the enzymes. 4. Neither alpha-C- nor N-oxidation is induced by pre-treatment with phenobarbitone or 3-methylcholanthrene.

Amphetamines↗
PubMed1978

Aromatic oxidation of some phenothiazines.

The previously reported N-oxidation products phenothiazine-N-OH, N-O. and -NOOH obtained upon chemical and metabolic oxidation of phenothiazine nuclei are now shown to be the C-oxidation products, 7-hydroxyphenothiazines, phenothiazin-3-ones and phenothiazin-7-ones which have the para-hydroquinoneimino and para-quinoneimino type systems. 2. The metabolism of various 2-substituted phenothiazines in vitro gave mainly ring-hydroxylated metabolites and sulphoxides. The phenolic metabolites were further oxidized to phenothiazones either as metabolites or as 'metabonates'. 3. After metabolism of chlorpromazine, nor1-chlorpromazine and nor2-chlorpromazine in vitro, phenothiazones ('pink compounds') were obtained as N-dealkylated products of the phenolic derivatives 7- or 3-hydroxy compounds. 4. The synthesis and physicochemical characteristics including t.l.c., u.v., g.l.c. and mass spectra of the oxidized phenothiazine nuclei and of 8-(N-methyl-anilino)-2-chlorophenothiazin-7-one are reported.

Animals↗
PubMed1977

The metabolism, distribution and elimination of chlorphentermine in man.

1 A gas-liquid chromatography procedure for the determination of chlorphentermine (I), N-hydroxychlorphentermine (II) and alpha,alpha-dimethyl-alpha-nitro-beta-(4-chlorophenyl)ethane (IV) in urine has been developed. Also methods are reported to determine conjugated II and the total N-oxidized metabolites of I, i.e. II, conjugated II, alpha,alpha-dimethyl-alpha-nitroso-beta-(4-chlorophenyl)ethane (III) and IV in urine. 2 The synthesis of alpha,alpha-dimethyl-alpha-nitroso-beta-(4-chlorophenyl)ethane (III) and its properties are reported. 3 The kinetics of urinary excretion of I and its metabolic products after the oral administration of I to a human subject on separate occasions have been studied. Under normal conditions of urinary pH, metabolism by N-oxidation was the main elimination route of I; acidifying the urine increased the urinary excretion of unchanged I at the expense of the N-oxidized products. 4 The importance of the N-oxidation metabolic route in the distribution of chlorphentermine (I) in man is discussed.

Adult↗
PubMed1977

Oxidation of aliphatic hydroxylamines in aqueous solutions.

The effects of pH, buffer constituents, duration of storage, presence of air, heavy metal ions, extracting solvents and various additives and cofactors on the aerial oxidation of some aliphatic primary and secondary hydroxylamines were investigated. Copper ions were particularly effective catalysts of the oxidation reaction. Conditions to minimize this transformation are described.

Chelating Agents↗