Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

M202 > W19 Overview of neurotransmission and therapeutic targets for CNS drugs > Flashcards

W19 Overview of neurotransmission and therapeutic targets for CNS drugs Flashcards

1
Q

What is a neurone? (Refresher)

A

Neurones are a particular type of cell that carry information messages or signals to and from the brain and the rest of the body.
Types: sensory, inter-neurone and motor neurone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

How do neurones work?
(process of depolarisation)

A

Resting-state (polarised):
Neurones stay at rest with their sodium ions on the outside of the cell body (soma) and potassium ions on the inside

Na+ Sodium ions
K+ Potassium ions

Excited state (depolarised):
Neurons get excited when the sodium ions rush inside (from outside), and potassium ions rush out (from inside) the cell body.
This rushing in and out causes
depolarisation and generates action potential (electrical impulse) racing down the axon.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

How does sodium/potassium move in/out in the neurone? (2)

A

Active transport: Sodium/Potassium ATPase pumps
Ion Channels (ionotropic/voltage-sensing & ligand-gated)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is/are the consequence(s) of neurone firing (electrical impulse/action potential)?

A
  1. Once the electrical impulse
    reaches the terminal button (axon),
    it triggers the vesicles (containing
    neurotransmitters) to move towards
    the terminal end and release
    neurotransmitters into the synapse.
  2. Neurotransmitters released from
    the pre-synaptic neurone bind to
    the receptors in the post-synaptic
    neurone and activate downstream
    signalling
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

The fate of neurotransmitters released from pre-synaptic neurone:

What can released NT do?(5)

A

Action potential generated/depolarisation opens the calcium channels in the pre-synaptic neurone and regulates the trafficking, docking and fusion of neurotransmitter-containing vesicles and also triggers the neurotransmitter’s exocytosis into the synapse.

The released NT can do one or more of the following,
* Bind to presynaptic receptors
* Bind to postsynaptic receptors
* Diffuse out of the synaptic cleft (diffuse into any neighbour cells, glial cells)
* Metabolise/degrade by enzymes
* Reuptake by the pre-synaptic transporters

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are the processes involved in neurotransmission?

A

Precursors (getting the raw materials)
* Biosynthesis(making the NTs)
* Storage (vesicles -Golgi bodies)
* Transport (neurofilaments and microtubules)
* Docking- vesicle and pre-synaptic membrane line up in a fusion-ready state
* Influx of Ca++
* Vesicle movement
* Exocytosis—(fusion and release)
* Crossing synaptic gap
* Binding postsynaptic receptors
* Reuptake mechanisms to recover NTs
* Deactivation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are the Major CNS drug targets? (4)

A
  • Ionotropic receptors (voltage-gated or
    ligand-gated)
  • Metabotropic receptors (GPCRs)
  • NT reuptake transporters
  • Enzymes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Examples of neurotransmitters and their ligand-gated Ion channels? (5)

A
  • Acetylcholine- Nicotinic AchR
  • ATP- P2X
  • 5-HT- 5HT-3 (serotonin)
  • Glutamate -AMPA, NMDA, kainate
  • GABA- GABAA receptors
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Key Features and Properties of Ion Channel?(3)

A
  1. Selective transmembrane pore
    (molecular sieve/filter)
    Charge & Size of the ions
    -Sodium channel will not permit potassium ions
    -K+ channels more selective to K+ than Na+
  2. Specific sensor for gating (open & close)
    (involves conformational change)
    - Membrane potential: Voltage-gated
    - Neurotransmitter binding: Ligand-gated
    - Temp & stretch: mechanosensitive
  3. Regulatory mechanisms
    -“inactivation” control (inbuilt)
    Abundance & location (e.g. postsynaptic density)
    Modulation (G proteins, 2nd messengers, protein kinases
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q
A

glutamate- orthosteric
memantine- allosteric modulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Advantages of Allosteric drugs? (3)

A
  • Offers novel pharmacological options of “fine-tuning” receptor function
  • intensify a weakened hormone/ NT signal caused by localised deficit
  • Clinically safer drugs with enhanced selectivity and reduced liability for receptor tolerance and/or desensitisation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is meant by the term Metabotropic receptors?

A

Ligand binds to it and activates it e.g. GPCR

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

(Metabotropic receptors)
GPCR- Effectors
What are the types of Ga subunits?

A
  • Gsa- Adenylyl cyclase- cAMP
    -Stimulatory (neurotransmitter release)
  • Gia Adenylyl cyclase cAMP Inhibitory
    (neurotransmitter release    )
  • Gqa Phospholipase C calcium Stimulatory
    (neurotransmitter release,

(Gbg subunits have effectors as well – e.g. potassium ion channels)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Examples of neurotransmitters and their GPCRs (Agonist/antagonist):

A

Acetylcholine= Cholinergic (Muscarinic)
Adrenaline/noradrenaline= adrenergic (alpha & beta)
Dopamine= dopaminergic
Serotonin= 5-HT
Histamine= H1, H2..
Endorphins =Opioid
Substance P= neurokinin (NK1)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Condensed:
How do drugs affect neurotransmission? (6)

A
  1. Synthesis
  2. Storage
  3. Release
    -AP and Ca entry
    -exocytosis
    -pre-synaptic receptors
  4. Signalling
  5. Metabolism
  6. Uptake
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Drugs altering neurotransmitter synthesis
Example:

A

Drugs acting at synthesis enzymes (either as an inhibitor or substrate)

  1. Inhibit rate-limiting enzyme
    e.g. a-methyl tyrosine
  2. Pro-drug substrate
    e.g. L-DOPA for Parkinson’s disease
  3. “False” substrate
    e.g. methyl-DOPA&raquo_space; methyl-NA (“false”
    transmitter)
17
Q

Drugs altering transmitter storage and release? (5)

A

Storage:
* Reserpine - disrupts storage of noradrenaline in vesicles
- blocks sympathetic neurotransmission

Release:
* Block action potential, voltage-gated Na+ channels - lidocaine
* Blocks Ca+ entry in presynaptic terminals- w-conotoxin
* Block vesicle exocytosis and NT release– botulinum toxin (bacterial toxin block the release of acetylcholine in cholinergic neurons)
* Activate presynaptic receptors – e.g. a2-adrenoceptor agonists

18
Q

Voltage-gated ion channels- Sodium Channel (Refresher)
Different confirmations? (3)

A
  1. Resting— depolarisation
    Open-Active confirmation
  2. Open-Inactive Confirmation
  3. Closed Confirmation

e.g. Lidocaine (local anaesthetic drug)
prefer to act on open, inactivated state only

19
Q

Voltage-gated ion channels- Sodium Channel
USE DEPENDENCY

Which drug classes exhibit a higher affinity for inactivated ion channels? (2)

A
  • The ion channel blockade is dependent on the rate of action potential discharge (the greater the frequency of firing, the greater the degree of blockade)
  • The following drug classes exhibit a higher affinity for inactivated ion channels
    -Anti-epileptics (phenytoin, carbamazepine, lamotrigine)
    -Anti-arrhythmic and local anaesthetics (disopyramide, procaine and lidocaine)
20
Q

What are the roles of a2-adrenoceptor agonistsand antagonists?
Examples?(3)

A

=Activate presynaptic receptors

  • Pre-synaptic alpha 2 receptors agonist
    = Promote the block of NT release (e.g clonidine, methyl dopa; centrally acting antihypertensives)
  • Pre-synaptic alpha 2 receptors antagonist
    = Promote the release of NT (e.g mirtazapine, for depression and OCD, promote noradrenaline and serotonin release
21
Q

Which drugs alter NT reuptake? (2)
How?

A

Cocaine & Tricyclic antidepressants (TCA) block noradrenaline reuptake transporter 1

22
Q

Which Drug class alters NT metabolism?

A

MAOIs

  • Neurotransmitter metabolism is mostly mediated via the enzymatic process (either at the synapse or inside of the pre-synaptic/post-synaptic neurone
  • e.g. Monoamine oxidase – breaks down noradrenaline, dopamine, serotonin 5-HT
    =inhibited by various anti-depressants e.g. iproniazid

MAOIs are an older type of antidepressant that are rarely used now

23
Q

Which drugs alter the postsynaptic neurone? (3)

A

GPCRs or ligand-gated ion channels:
* Agonist: Promote (mimic) NT action: =morphine- opioid receptor
* Antagonist: Block NT action:
=clozapine- dopamine, 5-HT2A, alpha1-adrenoceptor, and muscarinic-receptor
* Allosteric modulators: Enhance the effect of the endogenous NTs, benzodiazepines potentiate GABA
receptors

M202 (72 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions