neurodegenerative disease drugs

Parkinson's, Azheimer's, & MND

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Last updated: May 26, 2023

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First submitted	May 26, 2023
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Parkinson's Disease
what is Parkinson's disease characterised by?	what is Parkinson's disease caused by?	what does pharmacological treatment aim to do for Parkinson's?
insidious onset, with slowing of voluntary movement, muscular rigidity, postural abnormality & tremors	the striatal deficiency of dopamine following neuronal degeneration within the substantia nigra	restore dopamine levels in basal ganglia
		reduce the excitatory effect of acetylcholine
what drugs do we use to treat Parkinson's?	what are examples of each?	what is the mechanism of action of each?
dopamine precursors	levodopa	metabolic precursor of dopamine, that is converted to dopamine by aromatic L-amino acid decarboxylase (AADC)
inhibitors of dopamine metabolism	carbidopa	inhibits AADC in peripheral tissues to increase availability of levodopa in the CNS by allowing more to cross the BBB before being converted to dopamine
dopamine receptor agonists	bromocriptine, pramipexole, etc	agonists at dopamine D2 receptors, working to restore dopamine signalling in the striatum
antimuscarinic drugs	benzatropine	selectively blocks activity at the M1 muscarinic acetylcholine receptor, reducing cholinergic activity in the basal ganglia and restoring the ‘balance’ of acetylcholine and dopamine
amantadine	-	unknown, but thought to weakly inhibit the NMDA and nicotine receptors, as well as activate dopamine receptors
Alzheimer's Disease
what are the 3 distinguishing features of Alzheimer's disease?
accumulation of senile plaques (b-amyloid accumulations)
formation of numerous neurofibrillary tangles
loss of cortical neurons (especially cholinergic neurons)
what are the drugs used to treat Alzheimer's disease?	what is an example of each?	what is the mechanism of action of each?
acetylcholinesterase inhibitors	donepezil, rivastigmine, etc	preferentially inhibits acetylcholinesterase (AchE) in the CNS over peripheral enzymes
NMDA receptor antagonists	memantine	uncompetitive antagonists at glutamatergic NMDA receptors
Motor Neuron Disease
what is motor neuron disease?	a group of related neurodegenerative diseases that affect motor neurons and therefore voluntary muscle control
what is an example of a motor neuron disease?	amyotrophic lateral sclerosis (ALS) etc
what are the physical effects of motor neuron disease?	loss of motor neurons and muscle control until the patient can no longer eat, speak, move or breathe, with respiratory failure being the usual cause of death
what are the drugs indicated specifically for motor neuron disease?	riluzole, baclofen, edaravone, tizanidine
what are the mechanisms of action of the first drug thought to be?	binding to glutamate receptors to reduce the release of glutamate
	preferentially blocking TTX-sensitive sodium channels, which are linked to neuronal damage
	allosterically binding to GABAA receptors on post- synaptic neurons