8: ligand-target interactions 2

Question 1

What do serotonin receptors bind to?

Answer 1

serotonin, epinephrine, dopamine

Question 2

What is serotonin

Answer 2

neurotransmitter
tied to anxiety/depression, schizophrenia, OCD

Question 3

How is serotonin synthesized?

Answer 3

• L-tryptophan oxidized by tryptophan hydrolase (addition of alcohol)
• decarboxylated by amino acid decarboxylase
• monoamine neurotransmitter bc it has one amine group

Question 4

How does serotonin get degraded?

Answer 4

• can be oxidized to the carboxylic acid or reduced to the alcohol
• can also be converted to melatonin
• degraded by monoamine oxidases

Question 5

What are the three main strategies to target serotonin?

Answer 5

• inhibition of serotonin reuptake (SSRIs)
• inhibition of serotonin degradation (MAOIs)
• alteration of serotonin receptors (5-HT agonists/antagonists)

Question 6

How does serotonin reuptake occur (SSRIs)?

Answer 6

selective serotonin reuptake inhibitor
- prevent uptake of serotonin into presynaptic nerve ending
- if you block the site (reuptake transporter) of reabsorption located on the nerve ending, theres gonna be more serotonin in the synapse to be used.
- selective for the serotonin reuptake transporter
- theres receptors on the post-synaptic neuron that will create response in the post-synaptic response

Question 7

Describe the serotonin receptor family.

Answer 7

known as 5-HT receptors
- 7 different families

5-HT1
- inhibitory (GPCR)
- two different genes: 5-HT1a and 5-HT1b
5-HT2
- excitatory (GCPR)

Question 8

What is the difference between 5-HT1a and 2a?

Answer 8

they both regulate anxiety, but in opposite effects.
1a - inhibitory, which means it inhibits anxiety and to decrease anxiety, you will want to have an agonist.
2a - excitatory, which means that you will want to inhibit it to decrease anxiety

Question 9

What does 5-HT1a agonist drugs target?

Answer 9

anxiety and depressino

Question 10

What does 5-HT2a/2c antagonist drugs target?

Answer 10

migraine, depression, schizophrenia

Question 11

How do you measure selectivity?

Answer 11

= pKiab - pKiac

Question 12

How does ketanserin work as an antagonist?

Answer 12

• used for hypertension
• antagonist of 5-HT2a
  (shape and binding ability of hte small molecule determines stenth and type of interaction with protein)
• as ketanserin binds, it inhibits serotonin from binding to 5-HT2a

Question 13

Describe how Buspirone works.

Answer 13

• general anxiety disorder
• partial agonist of 5-Ht1a (also dopamine agonist)

Question 14

How do you compare selectivity?

Answer 14

• higher pKi value = stronger affinity = more selectivity/activation
• always relative to something else (compared)