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S J Grieve

Publications and source records attributed to S J Grieve.

12 recordsLinked to original sources
PubMed1988

Postnatal testing--a regulator's viewpoint.

In the UK the requirement to test animals for postnatal effects currently only applies to human medicines. The requirement was introduced in 1975 with general guidelines. They state that in the fertility and in some cases in the perinatal studies, in addition to testing the reproductive capacity of the offspring, the late effects of the drug on the progeny, in terms of auditory, visual, and behavioural function, should be assessed. Over the last 12 years this requirement has been interpreted very widely by the pharmaceutical industry. The postnatal studies submitted vary from the simple indices of physical development undertaken on some compounds to a wide variety of more complex behavioural tests undertaken on others. The types of postnatal tests presented on new chemical entity medicinal products are discussed, particularly those undertaken on drugs with therapeutic actions on the central nervous system. The results of the postnatal tests and their role in the assessment of the safety of new drugs are discussed.

Animals↗
PubMed1980

The rapid onset of functional tolerance to ethanol--role of different neurotransmitters and synaptosomal membrane lipids.

The rapid onset of functional tolerance to ethanol was studied in young adult mice of the TO Swiss and C57 Black strains. Drugs known to alter the metabolism of catecholamines and 5-hydroxytryptamine in mouse brain were without effect on the development of tolerance to ethanol. Amino-oxyacetic acid, which potentiates gamma-aminobutyric acid (GABA), slightly inhibited the development of tolerance, whereas the GABA antagonist, picrotoxin, produced a small increase in tolerance. The effects of treatments which altered synaptosomal membrane lipid composition were also investigated. Prolonged treatment of mice with diazacholesterol, an inhibitor of cholesterol synthesis, reduced the cholesterol content of synaptosomal membranes and, while not altering the initial sensitivity of mice to ethanol, prevented the subsequent development of tolerance. In contrast, feeding mice a diet rich in saturated fats throughout their lives reduced the unsaturated fat content of synaptosomal membranes and appeared to reduce the initial sensitivity of mice to ethanol. These results are consistent with our previous hypothesis that a reduction in unsaturation of synaptosomal membrane lipids underlies the rapid onset of ethanol tolerance in mice. They also provide further evidence for the suggestion that GABAnergic synapses may be particularly important in this respect.

Animals↗
PubMed1979

The rapid development of functional tolerance to ethanol by mice.

A method is described in which the development of tolerance to ethanol in individual mice can be measured during the inhalation of ethanol vapour. This method has been used with two behavioural end-points, loss of righting reflex and loss of rotarod performance. It demonstrates that, in the adult male, TO Swiss mouse, peak tolerance, in which approximately 2 X the original effective blood ethanol concentration is required to produce the behavioural end-point, can develop in 3--5 h. After this time the ability of the animals to perform normally in the presence of continued high concentrations of ethanol in blood begins to fall. The results are discussed in relation to current concepts of tolerance to central nervous system depressant drugs.

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