Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

DONE Drug Design and Discovery > Stephen Husbands - The Opioids > Flashcards

Stephen Husbands - The Opioids Flashcards

(42 cards)

Start Studying
1
Q

Pharmacological effects of Morphine are produced by the…

A

Alkaloids

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

Morphine is ____ due to it’s tertiary amino group

A

BASIC

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

The N-methyl group of Morphine can convert between the ___ and ___ positions

A

Axial and Equatorial

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

In order to see what functional groups were important for analgesia, chemists can create different ______

A

Analogues

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

Modifying or removing the 6 hydroxy group of Morphine does what to analgesic properties?

A

Doesn’t affect analgesia

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

Activity of Morphine is dependant on what 3 points?

A
  • Phenol ring
  • Aromatic ring
  • Tertiary amine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What happens to the tertiary amine of morphine when it interacts with it’s target site?

A
  • It is protonated and ionised - forms ionic bonds
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What interaction does the phenol of Morphine have with the target site?

A
  • Hydrogen bonding
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What interaction does the aromatic group of Morphine have with the target site?

A
  • VDW forces
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What bonding does the tertiary amine of Morphine have with the target site?

A
  • Ionic bonding - through protonated and ionised nitrogen
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are the 3 main types of opioid receptor?

A

Kappa, Mu and Delta

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Activation of which receptor results in the strongest analgesic effects?

A

Mu

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

Which receptor results in the strongest and most dangerous side effects? They are…

A

Mu

  • Resp depress
  • Addiction
  • Euphoria
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What does pharmacodynamics refer to?

A
  • Ability of drug to bind to it’s target and produce pharmacological effect
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

The phenol acts as a hydrogen bond…

A

Donor - forms bond with hydrogen bond acceptor in target site

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

The aromatic ring of morphine can form _____ forces with hydro____ sites in the binding site

A

VDW forces with hydrophobic sites in the binding site

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Pharmacokinetics refers to…

Study These Flashcards
A

Ability of drug molecule to reach target and survive in the body

18
Q

Morphine is relatively… polar or non polar?

19
Q

The amine group of morphine is a ____ base so morphine can exist in the free base and ionised form. What does this mean in relation to crossing the BBB?

Study These Flashcards
A
  • It is a WEAK base

- This means unionised form of Morphine can cross the BBB whereas the ionised form of Morphine cannot

20
Q

Once the free base of Morphine has crossed the BBB it must ____ in order to interact with the target binding site

21
Q

If the 6 Hydroxy group of Morphine is altered then the pharmaco____ of the molecule will change…

Study These Flashcards
A

PharmacoKINETICS

22
Q

Give an example of how changing the 6 hydroxy group of morphine will change it’s pharmaco______

Study These Flashcards
A

If the 6 hydroxy group of Morphine is made more NON polar e.g making it an acetyl group (6-acetylmorphine) then it is more able to cross the BBB and be absorbed due to it’s high lipophilicity, increasing it’s potency

23
Q

Heroin differs from Morphine in what way?

Study These Flashcards
A
  • The phenol has been acetylated
  • The 6-hydroxy group have been acetylated
  • It is more potent than morphine
  • The 3-acetyl group requires hydrolysis before it can interact with the receptor via H bonding (phenol group)
24
Q

Codeine undergoes what type of metabolism to form what?

Study These Flashcards
A

O-demethylation to form Morphine

25
Medicinal chemists tried altering the N-methyl group of Morphine and found what?
- Increasing the size of the change by adding a butyl group decreased activity - Increasing the size of the change past butyl increased activity slightly again - Adding a lipophilic phenethyl ring dramatically increased activity!
26
What did the addition of a lipophilic ring to the N-methyl group of Morphine suggest?
- That a hydrophobic binding region is present in the binding site
27
Nalorphine has an allyl group off the Nitrogen - what does this mean?
- It is an antagonist at the Mu receptor | - It is a weak agonist at the Kappa receptor
28
Removing the ring with the 6-hydroxy group results in the formation of...
Benzomorphans
29
Benzomorphans ____ analgesic activity
retain
30
List some different clinical difference between morphine and methadone
Methadone: - Less severe side effects - Less emetic effects - Less sedation - Less euphoria
31
Methadone is a __phenyl____amine
Diphenylpropylamine
32
Explain the test that was conducted with Naloxone to test for stereospecific binding...
- Naloxone radiolabelled - Measured binding under 2 conditions 1) XS non radiolabelled naloxone 2) XS non radiolabelled naloxone enantiomer Less binding in condition 1 More binding in condition 2 - as enantiomer doesn't specifically bind receptor - diff stereochemistry STEREOSPECIFIC BINDING PROVED
33
Morphine and enkephalins have WHAT in common?
Tyrosine skeleton (phenol attached to the ring through to the tertiary amine) - both interact with the same aspartic acid residue in the receptor site
34
The MESSAGE part of a molecule is responsible for what?
Pharmacological activity
35
The ADDRESS part of a molecule is responsible for what?
Target selectivity
36
Kappa specificity is due to WHAT?
- A basic nitrogen on the address part of the molecule
37
The presence of WHAT can make a nitrogen unable to protonate and therefore reduce kappa specificity and potency of the compound?
An oxygen - amide group. | As electrons interact with the carbonyl
38
Antagonism is due to presence of what?
- Cyclopropyl group off nitrogen on message - Cyclobutyl group off nitrogen on message - Allyl group off nitrogen on message (double bond)
39
Delta specificity is due to what?
- Aromatic ring presence on address
40
Mu specificity is due to what?
- Presence of double bond oxygen group off aromatic ring
41
What are the 4 strategies in developing Morphine analogues?
* variation of substituents (aromatic, nitrogen, 3-OH) * drug extension (adding chains to nitrogen to see if further binding sites present between analogue and receptor e.g hydrophobic region?) * simplification - remove rings of skeleton to see if needed or not for pharmacological effect * rigidification - add extra ring to increase rigidity - diels-alder adduct - Addition of ketone group and undertaking Grignard reaction adds acetylates 6-OH group and the ketone inc lipophilicity and inc potency
42
All analogues with the phenylpiperidine ring in the equatorial configuration are... ASK ???
antagonists - independent of the R group

DONE Drug Design and Discovery (9 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions