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Serotonin receptor confusion, esp. with mirtazapine

Work

Member
5+ Year Member
Feb 15, 2012
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It seems like overkill, but if your up at 3am because you are worried about useless, minute details then just read the "correspondence to clinical effects" section here:

http://en.wikipedia.org/wiki/Mirtazapine

I don't think he's "worrying about useless, minute details" as much as trying to understand the underlying mechanism of the drug, which reinforces the material better than strict memorization. It's not like his exam is 2 weeks out from today.
 
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Work

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Feb 15, 2012
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What does Mirtazapine's antagonism of 5HT1, 5HT2, 5HT3 do? How do they contribute to its effects as an antidepressant / sedative / appetite enchancer?

The TL;DR of that wikipedia link is that Mirtazapine is:
- an indirect agonist of central 5-HT1A receptors, which increases levels of 5-HT in the brain (antidepressive).
- an inhibitor of 5-HT2C in the VTA; 5-HT2C is responsible for inhibiting release of DA and NE in the reward zone. Inhibition of the 5-HT2C receptor disinhibits DA/NE release, resulting in antidepressant/appetite effects.
- a 5HT3 blocker, involved in antiemetic activity.
- a strong H1 inverse agonist a.k.a. an antihistamine (much like how diphenhydramine causes sedation) minus the anticholinergic effects seen with diphenhydramine. I think it binds to the inactive state of the histamine receptor, thereby blocking the release of histamine and causing sedation.
 

Old Style Nanny

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The TL;DR of that wikipedia link is that Mirtazapine is:
- an indirect agonist of central 5-HT1A receptors, which increases levels of 5-HT in the brain (antidepressive).
- an inhibitor of 5-HT2C in the VTA; 5-HT2C is responsible for inhibiting release of DA and NE in the reward zone. Inhibition of the 5-HT2C receptor disinhibits DA/NE release, resulting in antidepressant/appetite effects.
- a 5HT3 blocker, involved in antiemetic activity.
- a strong H1 inverse agonist a.k.a. an antihistamine (much like how diphenhydramine causes sedation) minus the anticholinergic effects seen with diphenhydramine. I think it binds to the inactive state of the histamine receptor, thereby blocking the release of histamine and causing sedation.

That makes a lot of sense now. Indirect agonist at 5-HT1A, of course.

What confused me was that very same Wikipedia page. Under pharmacology/binding profile, they have listed Mirtazapine as a strong antagonist at 5-HT1A. I should have actually read the clinical effects section below.

Thanks!
 
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