Drug design for the CNS Flashcards
(50 cards)
why are there so few drugs for neuropsychological diseases
pharmaceutical companies are decreasing their funding in CNS research programmes
why is less money being put into CNS research
No/little knowledge on underlying causes of the diseases
Harder to carry out clinical trials –> lots of side effects
Very hard to get drugs into the brain (BBB) –>we don’t know much about how to get the drugs past it
Direct brain infusion not ideal
Difficult to model the diseases in animals
why are CNS diseases difficult to target with drugs
Very hard to get drugs into the brain (BBB)
Difficult to target a disease when you don’t know its etiology (how the disease comes about)
animal models mainly used for CNS disorders
rodents
zebra fish
fruit flies
advantages of rodents as animal models
Mammalian –> lots of similarities in endocrine systems
Well characterized
easily genetically modified –> Humanized or introduction of mutations
Genome mapped –> we know their full genome
disadvantages of rodents as animal models for CNS diseases
Difficult to model many elements of CNS disorders e.g. delusions, mood and memory
Models/assays generally only test a single element of a phenotype –> CNS diseases are usually complex/many elements
Findings don’t always translate to humans
Rodents handle lipids differently to humans
Cant talk to the mice
how are transgenic mice used to test validation and efficacy of drugs
test whether that drug works on that specific target (knock out gene and see if it still performs function)
DREADD technology used in rodents for pharmaceutical production
Artificially introduce into the mice GM receptors
This enables you to specifically control activity of neuronal populations using artificial drugs
how do optogenetics work
Genetically modify the mice by implanting light emitting fibres into the brain to target specific neurons
creates light-sensitive ion-channels
categories of non-genetic models
pharmacological/surgical
behavioural
examples of behavioural models to induce stress
Maternal separation (early-life stress)
Acute stress (e.g. restraint, predator exposure)
Chronic stress
examples of pharmacological or surgical models
Neurochemical lesions e.g. MPTP
Middle cerebral artery occlusions
Drug administration
chronic stress can lead to
depression
effect of stress and anxiety on rodents brain
changes the way the rodents brain works
rodent more likely to be stressed or anxious as an adult
what does MPTP do
inject into rodents brain (substantia nigra)
specifically targets dopamine neurons
which disease can MPTP induce in mice
parkinsons
features of tests used to model depression and anxiety in rodents
conditioned or unconditioned
examples of unconditioned tests to model depression and anxiety
Open field Elevated plus maze /zero maze Barnes maze Social interaction Tail suspension Forced swim
examples of conditioned tests to model depression and anxiety
Conditioned startle
Learned helplessness
Active/passive avoidance
Defensive burying
what are behavioural tests used for
to assess markers of depression or anxiety in rodents
relationship between social interaction-ness and anxiety
the more anxious a rodent is, the less it will partake in social interaction with other animals
what do you measure in the social interaction test
overall locomotion
level of social interaction with other animal
variants of social interaction test
1, 2 or 3 chambers
e.g. stranger chamber and empty chamber
fluoxetine is an
SSRI (selective serotonin re-uptake inhibitor)
antidepressant drug
