7 - Antipsychotics Flashcards
Which subtypes of the 5-HT receptor are most pharmacotherapeutically important? What types of receptors are they?
- Subtypes 1, 2, 3, and 7
- All are GPCRs, except 5-HT3 is a ligand-gated ion channel
5-HT receptors (subtypes 1, 2, and 4-7) have ____ transmembrane domains
7
Where are 5-HT (subtype 1) receptor located? What are their functions?
- Located in CNS, CV, skin, and ileum
- Functions = behavioural, vasoconstriction, and vasodilation
Where are 5-HT (subtype 2) receptor located? What are their functions?
- Located in CNS, CV, respiratory, urogenital, and blood platelets
- Functions = behavioural, muscle contraction, and platelet aggregation
Where are 5-HT (subtype 3) receptor located? What are their functions?
- Located in CNS and PNS
- Functions = neuronal excitation, anxiety, and emesis
Majority of 5-HT receptors are _____, except ____ which is _____
Majority are post-synaptic, except 5-HT1 which is pre- and post-synaptic
Where is serotonin stored? When is it released into blood?
- Stored in platelets
- Released into blood when platelet activating factor concentration is less than 1 nM (too much vasodilation)
What are the most commonly prescribed migraine tx?
“Triptans”, potent agonists of 5-HT1B and 5-HT1D receptors
Why does agonism of 5-HT1B and 5-HT1D receptors cause migraine relief?
Causes constriction of cranial blood vessels and inhibition of pro-inflammatory mediators
What is buspirone?
Long-chain arylpiperazine, which is a non-selective 5-HT1A receptor agonist
What is chlorpromazine?
Typical antipsychotic
What are common structural features of typical antipsychotics?
- Either tricyclic or bicyclic w/ EW groups
- Tethered to chain w/ terminal amine
What are some side effects of second gen antipsychotics?
- Weight gain
- Movement effects (tremor, stiffness, agitation)
- Sedation
- Decreased sex drive and function
What is “modelling the pharmacophore”?
Using the receptor and seeing which ligands fit into it, and looking at what is important to each molecule for agonist activity
What are the 4 spheres for 5-HT3 receptor pharmacophores?
1) Hydrophobic group
2) Aromatic ring 1
3) Aromatic ring 2
4) Basic center (amine)