Neurological disease models Flashcards
Describe animal models in neurological disease
‘preclinical studies’
may start in vitro but leads to in vivo
Can be very long
Describe quality of animal models
Valid - If represents human condition
Reliable - Should be reproducible to obtain similar results
Describe preclinical data
Safety & tolerability
Pharmacokinetics
Tolerance (MTD, NOEL, MABEL)
SAD & MAD
Efficacy
Adverse side effects
What is MTD
Maximum tolerable dose
What is NOEL
No Observable Effect Level
What is MABEL
Minimal Anticipation Biological effect level
What is SAD and MAD
Single Ascending Doses
Multiple Ascending Doses
Why do CNS need a behavioural assay
Difficult to have a cell culture or computer model of something like an anxiety disorder
Usually first tested on rats and mice
Describe common anxiolytic drugs
Benzodiazepines (diazepam, triazolam, temazepam, lorazepam, chlordiazepoxide)
Zopiclone
Some only hypnotic effect (triazolam)
Describe Benzodiazepines
Increase effect of GABA on GABAa receptor (positive allosteric modulator)
Increase inhibition in CNS
Describe an elevated plus maze
Most commonly used models of anxiety
Don’t like outside so when spend more time out they work
Problems with modelling CNS disorders
How can you model OCD
Treatment depends on type of anxiety
EPM is an acute model while many disorders are chronic
Describe first line treatment
Cognitive-behavioural therapy
SSRI or selective-noradrenaline reuptake inhibitor
or both
Describe second line or adjunctive treatment
Pregabalin
Buspirone
How do pharmacokinetics of benzodiazepines
Application of many is affected by their pharmacokinetics (anxiolytic or hypnotics)
