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Here is a clear, organized summary of the notes from the image (Topic 27 - VMAT 2 Inhibitors):

VMAT 2 Inhibitors

What is VMAT?

VMAT = Vesicular Monoamine Transporter
It is a transport protein that moves dopamine into synaptic vesicles
It is NOT limited to dopamine - it also transports serotonin and other monoamines

Mechanism of VMAT 2 Inhibitors

Block the VMAT-2 transporter on vesicles
Prevent dopamine and serotonin from entering vesicles
This leads to decreased synthesis of adrenaline, noradrenaline, etc.
These drugs are also called dopamine depletors

Diagram Summary

Tyrosine (Ty) → DOPA → DA (Dopamine)
Dopamine normally enters the vesicle via VMAT-2
Inside the vesicle, DA is converted to NA (Noradrenaline)
NA is then released into the synapse
VMAT-2 inhibitors block the entry of DA into the vesicle, preventing this entire pathway

Drugs

1. Reserpine (Earliest VMAT-2 inhibitor)

Inhibits entry of dopamine into vesicles
Can be used to treat psychosis
Excessive dopamine reduction → Parkinsonism (side effect)
When dopamine doesn't enter → less noradrenaline produced → treats hypertension
Originally developed for hypertension
Problem: it is non-specific - also depletes serotonin → causes depression → many cases of suicide
Not used nowadays for this reason

2. Newer VMAT-2 Inhibitors (Dopamine Depletors)

Drug	Also Called	Use
Tetrabenazine	-	Huntington's chorea (dopamine excess)
Deutetrabenazine	-	Huntington's chorea
Valbenazine	-	Tardive dyskinesia only

Key Points:

Tetrabenazine and Deutetrabenazine are used in conditions with dopamine excess (e.g., Huntington's chorea)
Valbenazine is used specifically for Tardive dyskinesia
- Tardive dyskinesia is an adverse effect of antipsychotic drugs
- It involves supersensitivity of dopaminergic receptors
- Giving a dopamine depletor (valbenazine) manages this side effect
Valbenazine is the only drug approved for Tardive dyskinesia

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Explain this diagram nad drugs

Explain this

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Diagram: Noradrenergic (Sympathetic) Nerve Terminal

The diagram shows how Noradrenaline (NA) is made, stored, released, and taken back up in a sympathetic nerve terminal - and exactly where different drugs act to manipulate this process.

Key concept: The level of NA in the synapse controls sympathetic activity. More NA = more sympathetic action. Less NA = less sympathetic action.

The Normal Pathway (Step by Step)

Tyrosine (Ty)
     ↓  [Tyrosine Hydroxylase enzyme]
   DOPA
     ↓  [DOPA Decarboxylase]
   DA (Dopamine)
     ↓  [enters vesicle via VMAT-2]
  NA stored in vesicle
     ↓  [exocytosis - vesicle fuses with membrane]
  NA released into synapse
     ↓
  NA binds α and β receptors → sympathetic effect
     ↑
  NA reuptake back into nerve terminal (recycled)

Drug Sites of Action

Step	Drug	Mechanism	Effect on Sympathetic Activity
1	Metyrosine	Inhibits Tyrosine Hydroxylase enzyme - blocks conversion of Tyrosine → DOPA	↓ Decreased (less NA made)
2	Reserpine	Inhibits VMAT-2 transporter - blocks dopamine from entering the vesicle	↓ Decreased (no storage of NA)
3	Guanethidine	Inhibits exocytosis - blocks vesicle from releasing NA into the synapse	↓ Decreased (NA can't get out)
4	Cocaine / TCA	Inhibit reuptake of NA - NA stays longer in the synapse	↑ Increased (more NA at receptors)

Key Summary Points

Drugs 1, 2, 3 (Metyrosine, Reserpine, Guanethidine) all reduce sympathetic activity by reducing NA availability
Drug 4 (Cocaine, TCAs) increases sympathetic activity by blocking NA removal from the synapse
Released NA acts on two types of receptors on the postsynaptic membrane: α (alpha) and β (beta) adrenergic receptors
This is why TCAs (tricyclic antidepressants) cause tachycardia and hypertension as side effects - they block NA reuptake and amplify sympathetic tone

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