L8 - 5-HT - 3 IRL flashcards + 1 flowchart
Where does 5-HT come from?
Dorsal raphe nucleus and the gut - stored in platelets (5%)
Whats unique about 5-HT3?
Ligand gated channel
Whats unique about 5-HT1E?
Not found in rats - hence can’t do exp to figure out function
5-HT1 family is coupled to which G-protein?
Gi/0
5-HT2a,b,c is coupled to which G-protein?
Gq/11
5-ht4 is coupled to which G-protein?
Gs
5-ht5a is coupled to which G-protein? What about b?
Gi/0, B- none identified (has STOP codon)
5-ht6, 7 is coupled to which G-protein?
Gs
Why do SSRIs take time to work?
Too much 5-HT binds to 5-HT1 a,b,d autoreceptors - inhibiting release of 5-HT. Eventually autoreceptors are downregulated or desensitized - leading to increased 5-HT output. The need for downreg or desen. is why there is a delay in SSRIs effects.
Which 5-HT receptor is a target for LSD?
5-HT2A
Where are 5-HT2B receptors found?
Interstitial tissue of heart valves - none are found in the brain
Where are 5-HT2C receptors found?
Hypothalamus
Where are 5-HT2A receptors found?
Layer V of cerebral cortex
List 5-HT2A agonists (3) and antagonists (2)
Ag (Hallucinogenics): LSD, DOI, psilocybin
Antag (Antipsychotics): Clozapine (best antipsychotic as it has affinity to lots of receptors and transporters), atypical antipsychotics
List 5-HT2B agonists (3) and antag (1)
Ag: Fenfluramine (disrupting 5-HT vesicular storage of the neurotransmitter, and reversing serotonin transporter function) , Benflurorex, MDMA (ecstasy)
*Appetite suppressants BUT cause valvulopathies
Antag: Methysergide
*Migraine
!List 5-HT2C agonist and antagonist
Ag: Lorcaserin (anti-obesity. aids in treating addiction)
Antag: Agomelatine (TREATS depression, Generalized anxiety disorders (GAD))
*As it is a melatonin receptor agonist - you have to take it before going to bed rather than in the morning
Inverse Agonist
An agent that binds to the same receptor as an agonist but induces a pharmacological response opposite to that agonist. A neutral antagonist has no activity in the absence of an agonist or inverse agonist but can block the activity of either.
?Ergotamine
5-HT2B antagonist?
- Furthermore, it is an antagonist at the 5-HT2C receptor, while at the 5-HT1A receptor it serves as a partial agonist
- Also binds to 5-HT2A receptor
Atypical antipsychotics act at what R
D2, 5HT2A and many more
All triptans act as
5HT1B/1D agonists
*Triptans are a group (class) of drugs that are used to ease the symptoms of a migraine attack or cluster headache.
Antiemetics act as
5HT3 antagonists
What 5HT R agonism is banned because of its detrimental effects?
5HT2B
5HT2C agonist treats
Obesity
What 5HT R are not targets for any meds
5HT5 or 5HT1e
