The parkinsons note is Parkinsons
the treatments note is Anti-parkinsonians
Objectives:
to describe the neurochemical basis of drug treatments for PD to examine the most common drug treatments for the disease to consider the most common side effects of these drugs and their efficacy limitations
Dopamine in the brain
Dopamine is released by dopaminergic neurons, the main ones are in the substantia nigra (for movement and sensing) and the ventral tegmental area (Ffor cognition memory learning etc)
In parkinsons the substantia nigra atrophies and sends less dopamine
schizophrenia involves ventral tegmental area sending too much dopamine to nucleus accumines
Dopamine in the reward pathway
why does the brain do tonic signalling all the time
it allows membrane potantial to be at -80 allow pindrop signalling
rewards give phasic dopamine release
stimulus itself also gives dopamine hit, not reward itself
stimulus with no reward lowers dopamien release below baseline.
Dopaminergic circuitry in movement
neurons in the substantia nigra and striatum modulate neurons in motor cortex.
dopamine release leads to movement initiation in PMC
dopamien into striaum increases movement as activationi of striatum inhibits inhibitory globus pallidus which stops inhibiting thalamus which lets pmc to do shit
Parkinsons disease
parkinsons disease is characterised by a death of dopaminergic neurons in the substantia nigra, which is important for enabling movement.
with less dopaminergic neurons int he substantia nigra there will be less stimulation of neurons in the striatum (nigrostriatal pathway)
parkinson has a largely unknown aetiology
Biosynthesis of dopamine
L tyrosine is converted to L-DOPA which is then converted to dopamine
dopamine in disease
parkinsons is defined as too little dopamine from the substantia nigra so drugs for parkinsons increases dopamine levels (through increasing production or decreasing breakdown.)
drugs for parkinssons will heighten dopamine and have psychosis like symptoms
schizophrenia is defined as too much dopamine in the ventral tegmental are causing nuclaus accumbens activation
therefore drugs for dopamine will lower dopamine. and have parkinsons like symptoms
D receptor family
there are 2 classes
- D1 receptor family
- this encompasses D1 and D5
- increases cAMP production and
- K+ channel inhibition and Ca2+ activation and inhibition, depending on subtype
- D1 in striatum and neocortex D5 in hippocampus and striatum
- D2 receptor family:
- D2, D3 and D4 receptors
- Decrease cAMP production
- Decreased excitability via K+ channels
- Increased presynaptic inhibition via Ca2+ channels
- D2 in striatum, hippocampus and cortex; D3 in striatum, hippocampus and nucleus accumbens; D4 in cortex, striatum and hippocampus
Drugs for parkinsons
Drugs for parkinsons will increase dopamine in the brain
There is
- L-Dopa this is a substrate for dopamine which will be converted to dopamine which makes levels higher
- Enzyme inhibitors
- MOA-B (selegiline) this inhibits the enzyme which breaks down dopamine into noradrenaline increasing dopamine levels
- Dopamine agonists (ropinirole) this just acts like dopamine in the brain.
there are dopamine receptors throughout the body and these can be activated leading to side effects. using carbidopa mitigates this as it inhibits DOPA decarboxylase. it doesnt not cross the BBB so it will stop LDOPA from being turned to dopamine in the body but not the brain
all drug treatment for this disease is symptomatic and does not last.