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Neuropharmacology > Lecture 3 > Flashcards

Lecture 3 Flashcards

1
Q

What are agonists?

A

Receptor activators

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2
Q

What are antagonists?

A

Receptor blockers

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3
Q

What is a receptor?

A

A protein which binds to neurotransmitters, hormones etc and produces a cellular response

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4
Q

Name the two types of receptors

A
  • ionotropic - metabotropic
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5
Q

What is another name for iontropic receptors?

A

Ligand gated ion channels

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6
Q

What is another name for metabotropic receptors?

A

G-protein coupled receptors

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7
Q

Mechanisms of agonists

A

Binding to receptor -> AR complex -> conformational change of receptor= response

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8
Q

How do we measure responses to a drug?

A
  • muscle contraction- second messenger production e.g. cAMP, IP3 - inhibition of transmitter release - change in HR, BP etc
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9
Q

What shape is the agonist log concentration-response curve?

A

Sigmoidal

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10
Q

What is EC50?

A

Effective concentration giving 50% of maximal response

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11
Q

Why is there a maximum response?

A
  • finite number of receptors which are all occupied- response is proportional to the AR complex - property of tissue/cell e.g. maximal muscle contraction
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12
Q

What is affinity?

A

How well a drug binds to a receptor

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13
Q

What is efficacy?

A

A measure of the response once the drug is bound to a receptor

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14
Q

What is potency?

A

A combination of affinity and efficacy

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15
Q

Do drugs with the same EC50 always have the same efficacy?

A

No- drugs can have the same affinity but one drug can have higher efficacy than the other

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16
Q

What is Kd?

A

Concentration of drug required to occupy 50% of the receptors

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17
Q

What does a low Kd mean?

A

high binding affinity

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18
Q

Why can you not measure a response of ligand affinity?

A

Because you can have high affinity but low efficacy and vice versa- you have to look at binding

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19
Q

Mechanism of a ligand binding assay?

A

Displacement of radio-labelled ligand (3H, 14C, 125I) by a cool ligand

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20
Q

What is an issue of using a ligand binding assay?

A

Must account for non-specific binding e.g. to plasma proteins

21
Q

How do we deal with non-specific binding in ligand binding assays?

A

Increase amount of cold ligand to displace radio-labelled ligand, ensuring that only NSB only occurs with radio-labelled ligand

22
Q

Why do we see receptor desensitisation?

A
  • loss of receptors (internalisation) - exhaustion of mediators e.g. cAMP - physiological adaption (homeostatic response)
23
Q

What is tachyphylaxis?

A

rapidly diminishing response to successive doses of a drug, rendering it less effective

24
Q

What is the difference between desensitisation and tachyphylaxis?

A

Tachyphylaxis is a possible mechanism underlying desensitsation

25
Q

Examples of agonists used clinically

A

Adrenaline, salbutamol. dopamine, morphine

26
Q

What is a partial agonist?

A
  • cannot produce a full response (low efficacy) - prevents full agonists - reduces overactivity without reducing basal activity
27
Q

Why do we use buprenorphine (temgesic) as a partial agonist?

A
  • less abuse liability - less dysphoria
28
Q

What are inverse agonists?

A

Agonists that produce the opposite response of a full agonist

29
Q

Why do we use inverse agonists?

A

To reduce the constitutive activity (activity without a ligand) of GPCRs

30
Q

What would an inverse agonist do at the GABA-A receptor?

A

Decreases the activity of GABA

31
Q

What is a PAM?

A

Postive allosteric modulator

32
Q

What do PAMs do?

A

Increases coupling to a G protein which makes the agonist more effective

33
Q

What is a NAM?

A

Negative allosteric modulator

34
Q

What do NAMs do?

A

Reduce effectiveness of the G protein

35
Q

What is an AGO-PAM?

A

An agonist with positive allosteric modulatory activity

36
Q

Why would you use a PAM/NAM?

A

If you want to increase/reduce activity but don’t want to change the regular temporal pattern, modulate the activity of agonists

37
Q

What is a competitive antagonist?

A
  • reduces EC50 of an agonist - parallel shift in concentration-response curve - can still achieve a maximum response with increased agonists
38
Q

What is pA2?

A

A measurement of antagonist potency

39
Q

Define pA2

A

Negative log of the molar concentration of antagonist that reduces the effect of a known agonist concentration by half

40
Q

What does a larger pA2 value mean?

A

The better an antagonist is

41
Q

Why do we have to consider receptor selectivity for antagonists with high pA2 values?

A
  • higher pA2= less selective an antagonist is - risk of antagonising receptors which were not intended
42
Q

Examples of competitive receptor antagonists

A
  • naloxone - chlorpromazine - beta blockers - atropine - tubocurarine
43
Q

What is a non-competitive antagonist?

A
  • cannot be outcompeted - bind to allosteric site/covalently bound to binding site - no parallel shift or maximum response
44
Q

What is the importance of spare receptors?

A
  • allows max response without occupying all receptor (increased sensitivity) - maybe prevent exaggerated responses
45
Q

How do spare receptors affect Kd and EC50?

A

Kd ≠ EC50

46
Q

Examples of non-competitive antagonists

A
  • ketamine (NMDA) - perampanel (AMPA) - 𝛼-bugarotoxin (nicotinic)
47
Q

What is drug use-dependence (activity/frequency dependence)?

A

The more receptors a drug preferentially blocks, the more effective it is (basal activity is preserved)

48
Q

Examples of drugs with use dependence

A
  • epilepsy voltage gated Na+ channels (only block during overactive moments) - cardiac arrythmias Na+ channels (block over active rhythms)

Neuropharmacology (15 decks)

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