Drug targeting synapses

Question 1

What 5 stages drugs can target synapses?

Answer 1

1. synthesis
2. storage
3. release
4. interaction with receptors [best]
5. nt termination/nt inactivation

Question 2

Why is interaction with receptors the best way for drugs to target nt transmission?

Answer 2

• doesn’t interfere with synthesis of other molecules
• can promote or prevent binding to receptors on post-synaptic neuron
• many molecules have affinity for receptors

Question 3

How can synthesis of nt effect transmission?

Answer 3

• prevents nt being made
• this prevents nt being transmitted
• HOWEVER: may interfere with production of other molecules

Question 4

Give an example of drug targeting synthesis of nt

Answer 4

e.g. drug: Telotristat [prevents serotonin, 5-ht]
- tryptophan hydroxylase prevents from breaking down tryptophan to 5-hydroxytryptophan
- therefore no 5-hydroxytrypamine [serotonin]

Question 5

How can storage of nts effect transmission?

Answer 5

• preventing nts from package into vesicles
• unprotected nts broken down by enzymes

Question 6

Give an example of drug targeting storage of nts

Answer 6

e.g. drug: Reserpine [prevents 5-ht from entering vesicles via VMAT]
- leaving 5-ht unprotected in cytoplasm
- enzymes: monoamine oxidases (MAOs) break down monoamines [such as 5-ht, da]

Question 7

How can release of nt effect transmission?

Answer 7

• preventing release of nts into synaptic cleft
• cannot bind to receptors on post-synaptic neuron

Question 8

Give an example of drug targeting release of nt

Answer 8

e.g. Buspirone [antidepressant, reducing serotonin release via negative feedback by autoreceptors]
- buspirone = partial agonist at 5-ht1a autoreceptor
- autoreceptor stimulated = reduce serotonin release (negatively regulated)

Question 9

What are autoreceptors?

Answer 9

• regulate release of nts via a negative feedback mechanism
• when stimulated, they inhibit release of nt
• all are metabotropic receptors (GPCRs)

Question 10

State the difference between agonists and antagonsits

Answer 10

• agonists = affinity AND efficacy
  (can bind and also activate receptors - get response)
• antagonists = affinity, NO efficacy
  (can bind but do not activate receptors- no response)

Question 11

How can interaction with receptors effect nt transmission?-

Answer 11

• prevents (or promotes) nt binding to receptors at post-synaptic neuron
• receptors may be blocked [no signal sent]
• or blocked on the pre-synaptic neurone [no reuptake, prolongs nt in synapse = promotes binding to post-s neuron]

Question 12

Give an example of a drug targeting nt interaction with receptors

Answer 12

e.g. SSRIs (prevent serotonin from reuptake into pre-s neurone)
- this prolongs/increases conc of 5-ht in synapse
- promotes binding to receptors on post-s neuron

Question 13

How can nt termination effect transmission?

Answer 13

• removal of nts from synapse (prevents binding to receptors)
• nts removed by enzymatic degradation
• nts removed by simple diffusion (away from synapse)

Question 14

Give an example of nt termination

Answer 14

e.g. the reuptake of 5-ht via serotonin transporters [SERT]
e.g. enzymes that degrade nts = MAOA