Abilify (Aripriprazole) works by Partial Agonism on dopmine receptors.

[Petros Agapetos]

Location of D2 Receptors in the Human Brain
The different sub-types of D2 receptor possess broad and varied anatomical distribution patterns in the brain and periphery. D2 are highly expressed in the caudate, putamen (basal ganglia), nucleus accumbens, ventral tegmental area and the substantia nigra and in lower concentrations in the septal region, amygdala, hippocampus, thalamus, cerebellum and cerebral cortex. Specifically in the cerebellum the highest concentrations are in lobules IX and X.

D3 receptors have a more limited pattern of distribution and favor limbic expression such as the nucleus accumbens. Lower levels are detectable in the substantia nigra, ventral tegmental area, septal region, thalamus, cerebellum and cerebral cortex.

D4 has the lowest level of expression in the brain. It is found in moderate levels in the hippocampus, substantia nigra, nucleus accumbens, ventral tegmenta area, amygdala and frontal cerebral cortex.

Abilify is a dopamine D2, D3, and D4 partial agonist.

Schizophrenia is a disabling psychiatric disorder characterized by a myriad of positive, negative and cognitive symptoms that can be attributable to an imbalance between dopaminergic pathways that signal D2 and D1 receptors.

According to the classical theory, the positive symptoms of schizophrenia are attributable to hyperactivity of dopamine at D2 receptors in the mesolimbic pathway. This occurs in different stages including changes in dopamine synthesis, dopamine release, as well as the dopamine D2 receptors. Advances in neurochemical imaging studies have demonstrated that the presynaptic striatial dopamine availability is increased. Following this it has been observed that in schizophrenia the release of dopamine from the striatial synapse is also increased, leading to an increase in the baseline occupancy of D2 receptors by dopamine.

At the receptor level, an increase in striatial D2 and D3 receptor density in schizophrenic patients has been described. Alongside this, a higher sensitivity of existing postsynaptic dopamine D2 receptors and an increase in the proportion of dopamine D2 receptors that are in a high affinity state has been recorded.

Hypothetically, the negative and cognitive symptoms associated with schizophrenia are attributable to hypo stimulation of D1 receptors

[Dna8]

I found that it gave me Akathisia.

[Petros Agapetos]

I found that it gave me Akathisia.

Yes, it can cause psychomotor restlessness; but it subsides after you take it for a long while and your body gets used to the medication.

All antipsychotics can potentially cause this. But in the case of Abilify, akathisia happens more frequently. It is a small price to pay. Considering that Abilify is a partial agonist. Therefore its side effects profile is better than those of dopamine antagonists (which only block dopamine). Abilify causes less anhedonia (lack of pleasure) and lack of motivation than dopamine-blocking antipsychotics. Abilify is also approved for the treatment of depression (by adding Abilify to an antidepressant therapy).

Why did you have to take Abilify? If I might ask.

[Dna8]

Why did you have to take Abilify? If I might ask.

As you probably know, Abilify is one of those multi-functional meds..

It was prescribed to me because my affective difficulties were reminiscent of uni and bipolar depression both.. I guess the doc. wanted to accommodate the nuances (as he perceived them) in my case..

[Petros Agapetos]

Aripriprazole (Abilify) is a partial agonist on D2. Dissociate more easily from receptor than typical antipsychotics; better side effect profile.
Abilify (Aripriprazole) is a partial agonist on serotonin receptor: 5HT1A; this action causes dopamine to be released in the prefrontal cortex , thereby Abilify might treat negative and cognitive symptoms of psychosis, schizophrenia; reversing neuroleptic-induced deficit syndrome; caused by dopamine antagonists. Abilify is used after dopamine antagonist treatment, in order to treat the depression, anhedonia, and blunting of affect they cause. Abilify has more moderate side effects due to this reason as well.

Abilify reduces the activity of the mesolimbic (reward) pathway and increases the mesocortical pathway activity (good for treating negative and cognitive symptoms); Abilify is an antagonist on serotonin 5HT2A, which when activates *by an agonist* would increase dopamine release in the prefrontal cortex; thereby preventing dopamine release there.

As a partial agonist, Abilify, increases dopamine activity where it is low in the brain ; and reduces dopamine activity where it is excessive.
PARTIAL AGONISM ON D2: Treats Positive Symptoms
PARTIAL AGONISM ON 5HT1A: Treats Negative and Cognitive Symptoms
ANTAGONISM ON 5HT2A: Treats positive symptoms; Abilify blocks this receptor, which when activated by dopamine, would increase dopamine release in the prefrontal cortex (involved in executive mental functions, self-consciousness, and judgement, etc.). 5HT2A antagonism causes dopamine release in the nigrostriatal pathway, less motor side effects than with typical antipsychotics or antagonists of the second generation.

Consider a partial agonist for your treatment of mania, psychosis, schizoaffective disorder, schizophrenia etc.

Abilify reduces mesolimbic dopaminergic activity via partial agonism (60% on D2), which treats positive symptoms of psychosis (schizophrenia).

[Petros Agapetos]

I use Abilify to prevent mania and psychosis. I take 400mg every 3 weeks (~ 20mg / day).
Abilify covers 70% - 90% of dopamine D2 receptors. Activating the dopamine receptors 60% the activity of dopamine (partial agonist).
Abilify agonizes autoreceptors which turn off dopamine release from presynaptic neurons; dampening down dopaminergic activity.