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MODA MVST1b > Neuropharmacology IGNORE > Flashcards

Neuropharmacology IGNORE Flashcards

1
Q

Aripiprazol

A

Antipsychotic (atypical), D2 partial agonist, 5-HT1A partial agonist

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2
Q

Why is developing CNS drugs very difficult?

A

Aetiology of most CNS disorders is not well understood
Side effects of CNS active compounds are often unacceptable
Compounds must be able to cross the BBB

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3
Q

Describe the blood brain barrier

A

Thick basement membrane on which endothelial cells are linked together by tight junctions, preventing the free movement of substances out of the capillaries
Surrounded by astrocytic endfeet, further preventing drug penetration

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4
Q

How can drugs cross the BBB?

A

Non-polar
Amphipathic (hydrophobic or hydrophilic groups)
Transported by membrane transporters

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5
Q

Levodopa/L-DOPA

A

Substrate for DOPA decarboxylase
Used to treat Parkinson’s
Transported by BBB neural amino-acid transporter (unlike DA)

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6
Q

Domperidone

A

Antiemetic
D2/3 receptor antagonist
Used to limit levodopa-induced nausea
Peripherally restricted as pumped out across the BBB by multidrug resistance transporters (MDR1/p-glycoprotein)

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7
Q

In which conditions can the BBB become leaky?

A

Trauma, epilepsy, migraine

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8
Q

Which brain regions don’t have a BBB? Why?

A

Area postrema and circumventricular organs

Usually involved in sampling of humoral content/hormonal release/border ventricular system

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9
Q

How many CNS neurons?

A

10^11

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10
Q

Subtypes of glial cell?

A

NB More glial cells than neurons

  1. Astrocytes - maintain extracellular environment around neurons and synapses via reuptake systems. Also synthesise NTs.
  2. Oligodendrocytes - form myelin sheaths around axons
  3. Microglia - mphage like, provide immune defence activated by brain injury and disease pathology.
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11
Q

Name the 4 main parts of the neuron and their function

A
  1. Cell body - synthesises and processes proteins
  2. Dendrites - receive information
  3. Axon - enables transmission of AP from one neuron to another
  4. Presynaptic terminals - release molecules that diffuse across the synaptic cleft to the postsynaptic cell.
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12
Q

What are the physical types of synapse?

A
  1. Axodendritic
  2. Axosecretory (blood vessels)
  3. Axoextrafcellular
  4. Axosomatic
  5. Axosynaptic (other presynaptic synapses)
  6. Axoaxonic
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13
Q

Glutamate
Type
Action
Receptor

A 
Amino acid
Fast excitatory 
Ionotropic: AMPA/Kainate/NMDA
GPCR:
mGluR
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14
Q

GABA
Type
Action
Receptor

A

Amino acid
Fast inhibitory
Ionotropic GABA A/C
GPCR GABAB

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15
Q

Glycine
Type
Action
Receptor

A

Amino acid
Fast inhibitory
Ionotropic Glycine receptor

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16
Q

Dopamine
Type
Action
Receptor

A

Catecholamine
Modulatory
GPCR D1-5

17
Q

NA
Type
Action
Receptor

A

Catecholamine
Modulatory
GPCR alpha12 beta123

18
Q

5-HT
Type
Action
Receptor

A

Indolamine
Modulatory
GPCR 5-HT1247
Ionotropic 5-HT3

19
Q

Acetylcholine
Type
Action
Receptor

A

x
Modulatory
GPCR Muscarinic
Ionotropic Nicotinic

20
Q

Histamine
Type
Action
Receptor

A

x
Modulatory
GPCR
H1-3

21
Q

Name the neuropeptides
Type
Action
Receptor

A

Substance P, neuropeptide Y, endorphins, CTRH
GPCR
Neuromodulation

22
Q

Lipid mediators
Type
Action
Receptor

A

Prostaglandins, endocannabinoids, GPCR

Neuromodulation

23
Q

Gaseous
Type
Action
Receptor

A

NO CO
GC
Neuromodulation

24
Q

Neurotrophins, cytokines
Type
Action
Receptor

A

NGF, brain-derived neurotrophic factor, IL-1
Kinase-linked receptors
Neuronal growth, survival and functional plasticity

25
Q

Steroids
Type
Action
Receptor

A

Androgens, oestrogens
Nuclear and membrane receptors
Functional plasticity

26
Q

What is the difference between neurotransmission and neuromodulation?

A 
Transmission = fast = ligand-gated ion channel
Modulation = slower GPCR, or GC
27
Q

Define metabotropic

28
Q

Define ionotropic

A

Ligand-gated ion channel

29
Q

Define volume transmission

A

NT release from varicosities

Diffusion of NT a wider area involves non-synaptic localisation of receptors

30
Q

Define retrograde transmission

A

NTs may diffuse back to the presynaptic terminal to activate receptors

31
Q

Define paracrine transmission

A

NTs diffuse back away from the synapse to activate nearby cells

32
Q

How do you modulate synaptic communication?

A
  1. Inhibit NaV
  2. Reduce or enhance NT production in the terminal
  3. Inhibit presynaptic vesicular transport
  4. Displace transmitter from vesicles
  5. Inhibit KvS to lengthen AP and cause more release of NT
  6. Alter CaV to change the amount of vesicle exocytosis
  7. Block vesicle release machinery
  8. Agonists and antagonists
  9. Add or remove receptors
  10. Modulate receptors (ie phosphorylation)
  11. Change receptor subunits
  12. Inhibit presynaptic transmitter re-uptake
  13. Alter breakdown of transmitters in presynaptic terminal of synaptic cleft
33
Q

How do you synthesise glutamate?

A

GABA + alpha-oxoglutarate = glutamate + succinic aldehyde.

MODA MVST1b (11 decks)

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