Unwanted side-effects on the nervous system are occasionally seen both in clinical trials of new drugs, and during therapeutic use of marketed products. Most of the common adverse effects in humans are not easily identifiable in pre- clinical species. This area of safety is therefore of particular importance in the assessment of new potential pharmaceutical compounds and it has been included as part of the “core battery’ of assessment of vital organ functions in the ICH S7A safety pharmacology guidance document. The so called “Irwin test” was initially introduced as a rapid psychotropic screening procedure adapted from observations described first by Irwin in mice. Following modification Functional Observational Batteries (FOBs) were developed for use in other rodents and more recently adapted for use in the most common non-rodent species used in pharmaceutical development, which are usually the dog or the monkey. It is of particular importance when assessing neurobehaviour to carefully control and to standardise all factors involved in the test (the animal, the observer, the observation battery and environmental conditions) to make these data objective, repeatable and relevant for the species. Detailed neurobehavioural observation batteries were developed for use in pre- clinical species: rodents (rats and mice), dogs and non human primates. The rodent FOB assesses such functions as home cage and open field activity, stimulus reactivity, and neuromuscular functions. The dog FOB is focused on the interaction with humans and emphasises evaluation of gait, postural reactions and reflex functions. The monkey FOB has been developed from rodent and dog FOBs and it is considered to be the most suitable assessment when effects on higher-level cognitive and behavioural processes are expected with a direct relevance for humans. However some points such as social variables, ethical issues and costs need to be taken into account.
Neurobehavioural Assessment in Preclinical Species: Rodents, Dog and Monkeys
MOSCARDO, ELENA;GIAROLA, Alessandra
2006-01-01
Abstract
Unwanted side-effects on the nervous system are occasionally seen both in clinical trials of new drugs, and during therapeutic use of marketed products. Most of the common adverse effects in humans are not easily identifiable in pre- clinical species. This area of safety is therefore of particular importance in the assessment of new potential pharmaceutical compounds and it has been included as part of the “core battery’ of assessment of vital organ functions in the ICH S7A safety pharmacology guidance document. The so called “Irwin test” was initially introduced as a rapid psychotropic screening procedure adapted from observations described first by Irwin in mice. Following modification Functional Observational Batteries (FOBs) were developed for use in other rodents and more recently adapted for use in the most common non-rodent species used in pharmaceutical development, which are usually the dog or the monkey. It is of particular importance when assessing neurobehaviour to carefully control and to standardise all factors involved in the test (the animal, the observer, the observation battery and environmental conditions) to make these data objective, repeatable and relevant for the species. Detailed neurobehavioural observation batteries were developed for use in pre- clinical species: rodents (rats and mice), dogs and non human primates. The rodent FOB assesses such functions as home cage and open field activity, stimulus reactivity, and neuromuscular functions. The dog FOB is focused on the interaction with humans and emphasises evaluation of gait, postural reactions and reflex functions. The monkey FOB has been developed from rodent and dog FOBs and it is considered to be the most suitable assessment when effects on higher-level cognitive and behavioural processes are expected with a direct relevance for humans. However some points such as social variables, ethical issues and costs need to be taken into account.
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
