I went through the searches, there’s a lot of questions about SSRIs, SNRIs, ADHD medications, the mechanics of serotonin and dopamine but I didn’t see a whole ton on quetiapine.
In: Biology
Excuse formatting, on mobile. For the biohacker and psychopharm crowd I know I cut some corners, this info can obviously go on and on, tried to include enough to be technically correct, but not so much to bore op to death.
Quetiapine is particularly interesting.
Some terms though first:
Agonist/agonize: to go to a receptor in the brain or body and increase the inherent action. So a drug agonizing a serotonin receptor will tell your serotonin receptor to speed up, step on the gas.
Antagonist/antagonize: to go to a receptor in the brain or body and decrease the inherent action, step on the brake.
Partial agonist/partially agonize: to go to a receptor in the brain or the body and adjust the inherent action, if the inherent action is faster it will be slowed down and if the inherent action is slower it will be sped up, a cruise control.
Generally for our purposes we are talking about neurons, so we are using medications to speed up, slow down, or cruise control neurons rate of firing and releasing molecules like serotonin, norepinephrine, or dopamine, thus altering the communication and total communication between neurons.
Quetiapine:
At lower doses like 25 mg to 100 mg the most predominant action is on;
Histamine receptors as an antagonist, so mostly it causes sedation like Benadryl.
Around 300-800 mg add;
serotonin 2a antagonism (actually increase dopamine release)
serotonin 2c antagonism (acts as an antidepressant) which is also odd because the reverse action of agonizing 2c receptors by itself is an antipsychotic too.
serotonin 1a partially agonized (actually increase dopamine release)
dopamine 2 antagonism (this is the putative action of antipsychotics traditionally, that when we antagonize d2 receptors positive psychotic features tend to improve. This is probably the “main” way quetiapine works in regards to your question, but at this dose just barely doing this action)
Also some norepinephrine reuptake inhibition (antidepressant and may help fight se of the sedation from earlier recruited mechanisms of action)
Past 800 mg you get almost everything left in the kitchen sink;
serotonin 6 &7 antagonism (procognitive and antidepressant actions)
more serotonin 2a antagonism
way more dopamine 2 antagonism (so the main action is in full effect)
muscarinic m1 receptors antagonism (dry mouth, blurred vision, constipation, cognitive blunting, but protects against extra pyramidal symptoms)
Alpha 1 antagonism (sedation, orthostatic hypotension, possibly good for nightmares and anxiety).
We think the metabolic issues with meds like quetiapine are somehow propelled by the combination of the histone receptor antagonism and the serotonin 2c antagonism.
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