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Biomedical subjects

D R DAVIES

Publications and source records attributed to D R DAVIES.

At least 37 records · Page 2Linked to original sources
PubMed1961

Comparison of the functional effects of dyflos, tri-o-cresyl phosphate and tri-p-ethylphenyl phosphate in chickens.

Tri-p-ethylphenyl phosphate is unique amongst the organophosphorus compounds which produce neurotoxic effects in not being an inhibitor of cholinesterase. The dysfunction it produces is also marked by some unusual features. Thus it produces a characteristic high-stepping gait which develops at varying periods after intramuscular injection but more regularly following oral administration. A careful comparison of the character, onset and development of the effects of diisopropyl phosphorofluoridate (dyflos), tri-o-cresyl phosphate and tri-p-ethylphenyl phosphate has illustrated the differences between the two former substances and tri-p-ethylphenyl phosphate. It has also confirmed a previous suggestion that this substance acts in a different manner from the other two, a suggestion supported by the histological evidence.

Animals↗
PubMed1960

The relationship between the chemical structure and neurotoxicity of alkyl organophosphorus compounds.

Thirty-six alkyl organophosphorus compounds have been tested for neurotoxicity in the chicken. The individual compounds were chosen to enable the importance of each portion of the molecule to be assessed in relation to the property of neurotoxicity. Seventeen substances were found to be neurotoxic, fifteen for the first time. All of these contained fluorine. On the basis of the results reported, certain predictions have been made about the chemical structure of compounds which would be expected to be neurotoxic. The importance of fluorine suggests that it plays a direct role in the development of the biochemical lesion, and this may occur as the result of its being carried by the molecule as a whole to specific areas in the nervous system. By the action of cholinesterase, the P-F bond may be ruptured and ionic fluorine liberated where it blocks some metabolic cycle.

Animals↗
PubMed1959

2-Hydroxyiminomethyl-N-methylpyridinium methanesulphonate and atropine in the treatment of severe organophosphate poisoning.

The soluble methanesulphonate of the oxime 2-hydroxyiminomethyl-N-methylpyridinium (P2S) has been used to treat animals poisoned with sarin or ethyl pyrophosphate. The effect of the size of the dose, and its time of administration in relation to poisoning, have been examined. This oxime is very efficient in conjunction with atropine when given either before or after poisoning. About 30 mg./kg. seems to be the optimum therapeutic dose of the methanesulphonate. The significance of this optimum is discussed in relation to the treatment of accidental poisoning by organophosphate insecticides in man.

Animals↗
PubMed1959

Oximes of alpha omega-diquaternary alkane salts as antidotes to organophosphate anticholinesterases.

Sixteen compounds of the general structure {HON: CH.C(5)H(4)N(+).[CH(2)](n).R(+)}2Br(-) have been synthesized in which the position of the oxime group in the pyridine ring, the second charged group R(+) and the number of methylene groups between the charged atoms have been varied. The rate at which these compounds reactivate cholinesterase inhibited by ethyl pyrophosphate has been studied and a number have been found which are more active than 2-hydroxyiminomethyl-N-methylpyridinium methanesulphonate. Since considerable variation in structure was found among those compounds which are better reactivators than the latter, the concept that 2-hydroxyiminomethyl-N-methylpyridinium salts are unique in their ability to fit the surface of the inhibited enzyme is no longer tenable. The reactivating power of these oximes correlated well with their ability, when given in conjunction with atropine, to save the lives of mice poisoned by ethyl pyrophosphate. The most effective compounds, NN'-trimethylenebis-(4-hydroxyiminomethylpyridinium bromide) and NN'-hexamethylenebis(2-hydroxyiminomethylpyridinium bromide), contained a further oxime group in R(+), but the second oxime group was not essential for high activity. These new oximes were also superior in saving the lives of mice poisoned with sarin (isopropyl methylphosphonofluoridate), but the improvement was not as dramatic as when the mice were poisoned with ethyl pyrophosphate. The toxicity of the compounds varied with both n and R(+) and was unrelated to the therapeutic potency.

Alkanes↗
PubMed1958

The toxicity of 2-hydroxyiminomethyl-N-methylpyridinium methanesulphonate (P2S).

The toxicity of 2-hydroxyiminomethyl-N-methylpyridinium methanesulphonate (P2S) has been determined in a number of species by various routes. It is approximately equally toxic in the rat, mouse, and guinea-pig. It is much more toxic in the dog. Atropine influences the toxicity of P2S differently in different species. From the results obtained attempts have been made to assess the maximum safe dose which can be given intramuscularly to man.

Animals↗
PubMed1957

The association of blood cholinesterase levels with the susceptibility of animals to sarin and ethyl pyrophosphate poisoning.

An association between the blood cholinesterase (ChE) levels and the toxicity of sarin and ethyl pyrophosphate has been established. This has been demonstrated in two types of experiment. In the first, guinea-pigs were given a non-lethal dose of sarin (isopropyl methylphosphonofluoridate) which reduced the blood ChE to 20% of normal, and at intervals, as the ChE level of the blood gradually recovered, separate batches were given a second dose of the same size. A comparison was then made between the blood ChE levels immediately prior to the injection of the second dose and the mortality rate. In the second, a relatively small dose of sarin or ethyl pyrophosphate was given daily to rabbits until the enzyme value fell to a steady level. LD50 values were then determined on such groups and compared with those found in saline treated ones. In both guinea-pigs and rabbits it has been shown that a depression of blood ChE to below 40% indicated an increased toxicity of sarin and ethyl pyrophosphate to these species. The approximate quantitative relation appears to be that susceptibility is increased in the ratio 1.5 when the blood ChE is reduced by half.

Animals↗