Lecture 1 Part 2

Question 1

Amino acid transmitters: Glutamate.

Answer 1

→main excitatory transmitter
→ receptors abundant in cortex, basal ganglia, sensory pathways
→ four main receptor pathways: NMDA, AMPA, and kainate.

Question 2

NMDA receptors (presynaptic and postsynaptic)

Answer 2

→ role in synaptic plasticity (hippocampus)
→ role in memory, stroke.

Question 3

NMDA hyperactivation

Answer 3

→ epilepsy (lamotrigine)
→ stroke - neuronal damage caused by excess glutamate
→ neuropathic pain, drug abuse.

Question 4

Amino acid transmitters: GABA

Answer 4

→ main inhibitory transmitter in CNS (fast transmitter)
→ mostly via inhibitory interneurons
→ High density in nigrostriatal system.
→ GABA is synthesised from glutamate

Question 5

Devise drug to increase GABA.

Answer 5

GABA receptor agonists (e.g., benzodiazepines, baclofen)
• GABA reuptake inhibitors (e.g., tiagabine)
• GABA transaminase inhibitors (e.g., vigabatrin)
• Precursors and cofactors for GABA synthesis (e.g., glutamine, vitamin B6)
• GABA analogues (e.g., gabapentin)
• Allosteric modulators (e.g., neurosteroids, Z-drugs)
• Drugs that increase GABA release (e.g., levetiracetam)

Question 6

What conditions does BZD (benzodiazepines)?

Answer 6

1. Anxiety disorders (e.g., GAD, panic disorder)
   
   2. Insomnia (short-term)
   3. Seizures (e.g., epilepsy, status epilepticus)
   4. Muscle spasms (e.g., multiple sclerosis)
   5. Alcohol withdrawal (prevents seizures)
   6. Sedation (pre-surgery or procedures)
   7. Panic attacks (acute relief)
   8. Acute mania (bipolar disorder)
   9. Restless legs syndrome (improves sleep)
   10. Vertigo (e.g., Meniere’s disease)
   11. Catatonia (severe psychiatric conditions)
   12. Sleep disorders (e.g., night terrors, sleepwalking)

Used short-term due to risk of dependence.

Question 7

The diffuse modulatory systems of the brain

Answer 7

→FOUR SYSTEMS WITH COMMON PRINCIPLES:
-small set of neurons at core
-arise from brain stem
-one neuron influences many others
-synapses release transmitter molecules into extracellular fluid

→FOUR MAIN SYSTEMS:
-Noradrenergic (monoamine) Locus Coeruleus
-Serotonergic (monoamine) Raphe Nuclei
-Dopaminergic (monoamine) Substantia Nigra + Ventral tegmental area
- cholinergic basal forebrainand brain stemcomplexes

Question 8

Receptors

Answer 8

→ postsynaptic:
Carry on the message
→pre synaptic (autorecoptars):inhibit cell firing
Usually inhibitory
Negative feedback mechanism

Question 9

Drugs that increase noradrenaline

Answer 9

→ Mao enhancers
→ Na uptake inhibitors
→ A2 agonists
→ B receptor antagonists

Question 10

Monoamine transporters

Answer 10

→ 12 transmembrane domains
→ both ends intracellular
→ pump monamines in neuron
→ DA, na, 5HT transporters

Question 11

Monoamines: noradrenaline

Answer 11

-main action inhibitory (ß)
- also excitatory ( alpha/beta)
- termination: neuronal uptake and Mao
-In summary, noradrenaline is essential for stress response, attention, and mood regulation.