Case 10 pharmacology part 1

What is ACh function on the CNS?

• Alterness

• Attention

• Memory

How is ACh synthesised?

Choline + acetyl CoA -> ACh using the enzyme choline acetyl transferase

Where is ACh located in the CNS?

• Basal forebrain

• Cerebral cortex

• Hippocampus

What condition does an impaired levels of ACh cause?

Myasthenia gravis- autoantibodies to ACh receptors

ACh is also the neurotransmitter (NT) of the...

neuromuscular junction

What is ACh the final NT of?

ACH is the final NT in parasympathetic innervation pathways of the ANS

How is ACH recycles/ reuptaked?

ACh broken down to choline which is transported back into the pre-synaptic cleft for re-cycling into fresh ACh.

How is ACh cleared?

Acetylcholine esterase breaks ACh down before it activates receptors.

What are the ACh receptors?

1. Nicotine ACH R-ligand gated ion channels (fast)

2. Muscarinic ACh R-G protein coupled (slow)

3. Use 2nd messengers

What is noradrenaline function on the CNS?

• Alterness

• Arousal

• Action readiness

How is noradrenaline synthesised?

Tyrosine -> Levodopa -> dopamine -> noradrenaline

Where is noradrenaline located in the CNS?

• Medulla

• Solitary nucleus

• Locus coeruleus

What condition does an impaired levels of noradrenaline cause?

Sympathetic hyper-activation (multiple systems)

What is noradrenaline's role on the sympathetic nervous system?

• It is the major NT in the SNS

• Plays a major role in sympathetic innervation to the cardiovascular system

• Controls vasomotor tone by activating alpha-adrenoceptors on VSMC.

How is noradrenaline recycles/ reuptake?

Noradrenaline (NorAd) transport into pre-synaptic cell or glia by noradrenaline transporters (NET).

How is NorAd cleared?

NorAd broken down by monoamine oxidase in cytosol (NOT synaptic cleft) + by catechol-O- methyltransferase

What are the NorAd receptors?

1. beta-adrenoceptors (1-3)

2. Gs- coupled

3. Alpha-adrenoceptor 1 (Gq- coupled)

4. Alpha- adrenoceptor 2 (Gi/O coupled)

What is dopamine function on the CNS?

• Executive function

• Motor control

• Motivation

How is dopamine synthesised?

Phe -> Thy -> Levodopa -> Dopamine

Where is dopamine located in the CNS?

• Substantia nigra

• hypothalamus

• VTA

• Arcuate nucleus

• Zona incerta

What condition does an impaired levels of dopamine cause?

• Parkinson's disease (destruction of dopaminergic neurons in the substantial nigra)

• Multiple sclerosis

• Brain ageing

What type of behaviour is dopamine important in?

• Reward-motivaiton behaviour

• Many addictive drugs block dopamine re-uptake + increase its release

What does dopamine also influence?

• Motor control

• lactation (inhibit)

• nausea

How is dopamine recycles/ reuptake?

Dopamine transport into the presynaptic cleft or glia via dopamine transporters + monoamine transporters

How is dopamine cleared?

Dopamine is broken down by monoamine oxidase in the cytosol (NOT cleft) + catechol- O methyl transferase

What are the dopamine receptors?

• 5 subtypes (all GPCR)

• Different effects due to 2nd messenger system triggered after dopamine activation of receptors.

What is noradrenaline function on the CNS?