Abilify and dopamine / norepinephrine rui’s

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I was wondering if anyone else is on abilify or any other atypical antipsychotic. Abilify is unique in that it doesnt effect the d1 receptor but the d2. And also works on many seratonin receptors. It also blocks the DAT protein from working. I notice i dont get the euphoria from amphetamine or any substituted cathinone/amphetamine but notice the norepinephrine effects. From wikipedia it shows that abilify is actually a d2 agonist so im wondering if the main blockage of the dopamine response is due to its effect on the DAT protein.

Positive symptoms of schizophrenia (e.g. hallucinations and psychosis) are caused by an overactive mesolimbic pathway, which is one of the dopaminergic pathways in the brain. Antipsychotics are designed to alleviate those symptoms by reducing excessive dopaminergic activity in that pathway. Most antipsychotics do so by being D2 receptor antagonists.

Aripiprazole is a newer antipsychotic that works a bit differently: it lowers dopaminergic activity by being a D2 partial agonist. It means that aripiprazole binds the D2 receptor and does elicit an intracellular response, however this response is significantly weaker compared to full agonists (dopamine in this case). Thus when a partial agonist (aripiprazole) competes with a full agonist (dopamine) for a set of a given receptor, the overall response is weaker than full agonists alone. So despite its misleading agonist activity, aripiprazole does decrease dopaminergic activity in the mesolimbic pathway, alleviating positive symptoms of schizophrenia just like other antipsychotics.

Now it’s not surprising that the euphoria you experience from stims is weaker because it relies on dopaminergic activity in… the mesolimbic pathway. Many drugs (stims but also alcohol, nicotine, opiates, PCP, THC…) induce euphoria by increasing extracellular concentrations of mesolimbic dopamine. However this increase in extracellular dopamine is not as effective if its receptors are blocked or already occupied by less potent agonists, which is your case due to aripiprazole. Hope it makes sense.

Idk much bout the antidepressant world but I’m taking an epinephrine and norepinephrine inhibitor (it’s actually a selective a2 adrenoagonist, but the main function is inhibiting epinephrine and norepinephrine as a means of sedation). It’s somewhaf sedative and relaxing, but has almost no eurphoria and is very hypnotic. Idk if this is related to what you’re looking for

Nope, you are not right, certain D2 agonist behave as paradoxical antagonists because they only agonise presynaptic receptors, and that’s where their main mechanism of action comes from

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