I'm kind of lost on the difference between typical and atypical antipsychotics

Bailey

Active member
I'm kind of lost on the difference between typical and atypical antipsychotics. My understanding is that they all block dopamine receptors (D2 but D1?) and atypical are also act on 5HT2 (mostly 5HT2A?). Can someone clear things out please?
 

Alfredo

Well-known member
Yes sure. So typical antipsychotics are D2-Receptor Antagonists, their antipsychotic effect correlates with their affinity to the D2 receptor, while the atypical antipsychotics are not strictly bound to act via D2 receptor antipsychotic and as you said the antagonism on the 5HT2A Receptor is essential for the antipsychotic effect of the atypical.
 

Bailey

Active member
Yes sure. So typical antipsychotics are D2-Receptor Antagonists, their antipsychotic effect correlates with their affinity to the D2 receptor, while the atypical antipsychotics are not strictly bound to act via D2 receptor antipsychotic and as you said the antagonism on the 5HT2A Receptor is essential for the antipsychotic effect of the atypical.
Okay.
 

Alfredo

Well-known member
So if a drug has more affinity to 5HT2A than D2 its atypical (there are exceptions like aripiprazole).
 

Alfredo

Well-known member
Erm so the extrapyramidal motoric issues like dyskinesia, really bad stuff, torturous, that's from the effects on other areas in the brain.


See there are 4 main pathways for dopaminergic signals:- nigrostriatal, tuberoinfundibular, mesolimbic and neocortical.

And because of the effects on the nigrostriatal system, you have those Parkinson-like and other motoric symptoms
 

Alfredo

Well-known member
And because of the effect on the tuberoinfundibular system there is a prolactin increase and gynecomastia.

Yes, I mean you don't give dopamine agonists and antagonists together right.
 

Bailey

Active member
And because of the effect on the tuberoinfundibular system there is a prolactin increase and gynecomastia.

Yes, I mean you don't give dopamine agonists and antagonists together right.
That would result in some chaos but how?
 

Alfredo

Well-known member
@Ezra D2 receptor plays a big role, as you can still give Parkinson patients antipsychotics but you would use those with relatively low affinity to D2 -receptors.
 

Ezra

Active member
Cariprazine is an antipsychotic that acts more like a dopamine receptor agonist (medium-high efficacy D3 partial agonist, high selectivity compared to other antipsychotics) so maybe that could be used in people with Parkinson

~60% IA I believe
 

Alfredo

Well-known member
See you want the D2 blockage in the mesolimbic-neocortical system: antipsychotic effect but you also get: D2 blockage nigrostriatal: extrapyramidal motoric issues D2 blockage hypothalamus : hypothermia D2 blockage area postrema : anti emetic D2 blockage tuberos infundibular: hyper prolactinaemia and also H1 antihistaminic : sedation, weight gain alpha 1 blockage : vasodilatation 5HT2 : minor Extrapyramidal issues M-acetylcholine: minor extrapyramidal issues, atropine-like
 

Alfredo

Well-known member
@Ezra Yea see the partial agonism in those newer drugs like Cariprazine and even Aripiprazole is that idea that: if you have too much dopamine it will act as an antagonist and act antipsychotic, but when there is less dopamine around they don't block but rather help the dopamine act so there is hopefully less of that extrapyramidal motoric problems with those newer antipsychotics that also act as partial agonists on Dopamine receptors
 

Ezra

Active member
Yeah it keeps the dopamine receptor activation at a more constant level.
Also, H1 and M3 are possibly involved in hyperglycemia.
Tri/tetracyclic are some nasty mfers.
 

Ezra

Active member
Muscarinic acetylcholine receptor antagonism causes extrapyramidal side effects? I was under the impression that M1 antagonism can reduce extrapyramidal sides.
 
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