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Biomedical subjects

S J Grieve

Publications and source records attributed to S J Grieve.

9 recordsLinked to original sources

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

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.

Air