Aripriprazole (Abilify) is a Dopamine Partial Agonist

[Truthometer]

FGA = First Generation Antipsychotic
APZ = Aripiprazole (Abilify)
DA = Dopamine

Aripiprazole (Abilify) is a dopamine partial agonist on receptors D2, D3, and D4. Aripriprazole, due to its partial agonism on D2-like receptors, has the ability to lower dopaminergic activity where it is in excess (Mesolimbic Pathway) and raise dopaminergic activity where it is deficient (Mesocortical Pathway). Aripriprazole is a 5HT1A partial agonist [68%]. This causes dopamine release in the prefrontal cortex (PFC). This potentially treats negative symptoms as well as cognitive deficits as well as depression. Aripriprazole is an adjunctive treatment for treatment-resistant depression (typically added to an antidepressant, like an SSRI). Aripriprazole is also a 5HT2A antagonist, which causes dopamine levels to go up in the nigrostriatal pathway and offsets the functionally antagonist actions of Ariprprazole on some subpopulations of D2 receptors, whereas on other subpopulations, the intrinsic activity of Ariprirazole is up to 75%. Aripriprazole works to reduce positive symptoms by lowering dopaminergic activity in the mesolimbic pathway. Aripriazole treats negative and cognitive symptoms by raising dopaminergic activity in the mesocortical pathway.

Source: https://en.wikipedia.org/wiki/Aripiprazole

 

[AlphaMethylPhenyl]

As far as I know, the improvement in negative symptoms is just theory. Even Haldol from the 1950's is a 5-Ht1a partial...Clozapine probably has the most data behind it in that respect, but there is no medication indicated for negative symptoms.

Clozapine is the best AP we have. The other 15 or so aren't significantly different in efficacy (that's right, thorazine right up to vraylar or whatever is the most recent). But in terms of tolerability, the second-gen Ap's like Abilify might be better.

Abilify can cause some nasty restlessness, from what I know.

It's a partial agonist, but only to a small extent--or it wouldn't be an effective AP. At lower doses it doesn't work as much of an AP.

As it may be called a "3rd-gen" AP due to D2 partial activity, it is the first of such available in generic form the soonest. I believe the patent was filed in 2002 for schizophrenia. It's available as generic since 2015.

 

[Truthometer]

Dopamine antagonist antipsychotics (most antipsychotics) do not treat negative nor cognitive symptoms. In fact, they make them worse, with the possible exceptions of Abilify (Aripriprazole), Rexulti (Brexiprazole), and Vraylar (Cariprazine) which are partial agonists. Negative symptoms and cognitive deficits are hypothesized to be due to lack of D1 receptor stimulation, particularly in the mesocortical pathway connecting the VTA to the frontal cortex. Drugs which are 5HT1A agonist, cause dopamine release in the prefrontal cortex. Partial agonists have the potential to regulate dopaminergic neurotransmission in a way a flat agonist can't. Partial agonists can raise transmission in areas of the brain which are deficient in dopamine.

Sometimes, dopamine agonists are given to people suffering from anhedonic depression: such as Pramipexole which is a dopamine partial agonist (70% on D2 receptors). used in the treatment of treatment-resistant depression, negative symptoms (avolition, anhedonia, lack of motivation, blunting of affect, etc.), sexual dysfunction caused by SSRIs. Other agonists include anti-Parkinson's agents (Ropinirole, Bromocriptine). Low doses of dopamine agonists might be useful in treating anhedonia (lack of pleasure).

Trintelix is a 5HT1A full agonist antidepressant. Could be useful in dis-inhibiting dopamine release in the prefrontal cortex, treating negative symptoms. Trintelix is also a selective serototnin reuptake inhibitor.

 

[AlphaMethylPhenyl]

The hypothesis in "2nd-gen" AP's is that 5-HT2a antagonism increases D in the prefrontal cortex/frontal lobe overall.

They aren't D1 partials, but D2 partials. D1 agonism in the cortical system is what's thought to reduce negative effects--for clozapine, glutamate likely.

AP's only augment antidepressants. They aren't used for depression themselves.

Trint. is mostly an SSRI. That produces antidepressant effects. 5-HT1a may have impact on negative symptoms (not as much as 5-HT2a antagonism) but it's not antidepressant effects by itself.

 

[Truthometer]

APZ = Aripriprazole (Abilify)

• What are the implications of D2 partial agonism? Aripiprazole binds to the D2 receptor with the same affinity than dopamine, but has a lower intrinsic efficacy, so the response it triggers is lower than dopamine but higher than an antagonist. Through partial agonism, Aripriprazole reduces dopaminergic neurotransmission in the mesolimbic pathway.

• One postulated mechanism of action of aripiprazole in schizophrenia is the ability of the drug to increase dopaminergic activity from a subnormal level to normal activity in the mesocortical pathway [1].

 

[AlphaMethylPhenyl]

No except normal spikes in particular enjoyments in life are mysteriously omitted.

 

[etcccc]

(I?m just re-reading it now... I feel like there were too many disparate ideas in that post of mine. Perhaps I should chop it up and re-structure it into a few new threads, because I really am interested to know more about all of these questions, but I know that much of it wasn?t directly relevant to the discussions here. Suffice it to say it was my first post and I got a little overzealous...)