多巴胺受体部分兴奋作为抗精神病药的作用机制

在本文中，您将了解多巴胺部分痛苦。阿立哌唑（Abilify）和雷克多（brexipiprazole）最能说明这种作用。这些第二代抗精神病药/非典型抗精神病药与众不同atypical antipsychotics由于不同的作用机制。

阿立哌唑有什么不同？

The majority of second-generation (atypical) antipsychotics block the D-2 (dopamine-2) receptors but also usually equally as much block the 5HT-2a (serotonin-2a) receptors). The second-generation antipsychotics such as risperidone, ziprasidone, and paliperidone are all potent antagonists of dopamine D2 receptors while clozapine and quetiapine are weak D2 antagonists.

根据内源性多巴胺水平和信号状态，阿立哌唑可作为多巴胺D2受体（D2Rs）的完全拮抗剂、中度拮抗剂或部分激动剂，与所谓的偏倚配体药理学一致。

Why Is Aripiprazole Classified as an Atypical?

原因是阿立哌唑clinical action: its risk for certain neurological adverse effects such as episodes of acute muscular rigidity (dystonia) or involuntary abnormal movement disorders (dyskinesia) is low, which earns it accolades as an atypical; as opposed to antipsychotics with a high risk for this type of adverse effects, which are classified as typicals.

阿立哌唑是一种多巴胺部分激动剂，与阿立哌唑相反dopamine像大多数第一代抗精神病药物一样的拮抗剂或阻滞剂。

Dopamine Antagonism

Dopamine is one of the neurotransmitters found at the level of the synaptic space, space in-between neurons. Dopamine is released in the synaptic space from vesicles housed in the pre-synaptic neuron, then binds to dopamine receptors at the level of the postsynaptic neuron. Think of this as a key and lock type of effect where dopamine receptors are locks that open when the dopamine “key” enters the lock.

精神分裂症的一个假设是，在大脑的某些部分，突触中有过多的多巴胺。这个positive symptoms精神分裂症的思想be a result of all these “extra” dopamine molecules binding to dopamine receptors.

Dopamine antagonists bind to the dopamine receptors, thus block dopamine binding. And without the proper key, i.e. dopamine, the lock does not open; in other words, as the dopamine excess problem is corrected at the level of the synapse there are no ill effects (positive symptoms) resulting from it.

The problem though is that the dopamine blockade occurs all over the brain while the dopamine excess in schizophrenia is limited to specific parts of the brain. Further, in schizophrenia, while some parts of the brain are subject to dopamine excess, other parts are in fact experiencing a dopamine deficit.

This is why these medications, while effective for positive symptoms due to blocking of receptors in brain regions having too much dopamine, tend to also increase阴性症状, cognitive issues, as well as the risk for parkinsonism in patients taking them, due to blocking of dopamine in brain regions where there is too little dopamine. A potential solution to this problem is using partial agonists.

Dopamine Partial Agonists

A dopamine partial agonist is a molecule that binds to the receptor and partially activates it. Think about it as a key that sorts of fit in the lock so that the door can be wriggled about but not completely open.

多巴胺部分激动剂的作用比多巴胺的全部作用小，但比完全没有作用大，当受体被完全阻断时就会发生这种情况。换句话说，部分效应。

这种局部效应意味着，当阿立哌唑（一种多巴胺部分激动剂）周围多巴胺过多时，通过占据受体上的多巴胺空间并部分激活它们，实际上会降低过量多巴胺的作用。

这也意味着，当周围多巴胺太少而无法激活所有可用受体时，阿立哌唑实际上会与未被占据的受体结合，其作用（即使只是部分作用）现在被加到突触中的多巴胺效应中，从而使多巴胺剥夺的突触的多巴胺能效应净增加。

综上所述，阿立哌唑作为多巴胺部分激动剂，是多巴胺作用的调节剂。当存在时，它会减少多巴胺过量（当多巴胺过多时减少多巴胺作用）和多巴胺不足（当多巴胺过少时增加多巴胺作用）的影响。