Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles.

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Nasrallah HA

Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles.

Mol Psychiatry. 2008 Jan;13(1):27-35. Epub 2007 Sep 11.

PubMed ID

17848919 [View in PubMed

]

Abstract

非典型抗精神病药物提供几个值得注意的benefits over typical antipsychotics, including greater improvement in negative symptoms, cognitive function, prevention of deterioration, and quality of life, and fewer extrapyramidal symptoms (EPS). However, concerns about EPS have been replaced by concerns about other side effects, such as weight gain, glucose dysregulation and dyslipidemia. These side effects are associated with potential long-term cardiovascular health risks, decreased medication adherence, and may eventually lead to clinical deterioration. Despite a greater understanding of the biochemical effects of these drugs in recent years, the pharmacological mechanisms underlying their various therapeutic properties and related side effects remain unclear. Besides dopamine D(2) receptor antagonism, a characteristic feature of all atypical antipsychotic drugs, these agents also bind to a range of non-dopaminergic targets, including serotonin, glutamate, histamine, alpha-adrenergic and muscarinic receptors. This review examines the potential contribution of different receptors to metabolic side effects associated with atypical antipsychotic treatment for all seven agents currently marketed in the United States (risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole, paliperidone and clozapine) and another agent (bifeprunox) in clinical development at the time of this publication.

DrugBank Data that Cites this Article

Drugs

Aripiprazole

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Aripiprazole	5-hydroxytryptamine receptor 1B	Protein	Humans	Unknown	Antagonist Ligand	Details
Aripiprazole	5-hydroxytryptamine receptor 1D	Protein	Humans	Unknown	Antagonist Ligand	Details
Aripiprazole	5-hydroxytryptamine receptor 1E	Protein	Humans	Unknown	Antagonist Ligand	Details
Aripiprazole	5-hydroxytryptamine receptor 2C	Protein	Humans	Unknown	Antagonist Partial agonist	Details
Aripiprazole	5-hydroxytryptamine receptor 3A	Protein	Humans	Unknown	Antagonist	Details
Aripiprazole	5-hydroxytryptamine receptor 6	Protein	Humans	Unknown	Antagonist	Details
Aripiprazole	5-hydroxytryptamine receptor 7	Protein	Humans	Unknown	Antagonist Partial agonist	Details
Aripiprazole	Alpha-1A adrenergic receptor	Protein	Humans	No	Antagonist	Details
Aripiprazole	Alpha-1B adrenergic receptor	Protein	Humans	No	Antagonist	Details
Aripiprazole	Alpha-2A adrenergic receptor	Protein	Humans	No	Antagonist	Details
Aripiprazole	Alpha-2B adrenergic receptor	Protein	Humans	No	Antagonist Ligand	Details
Aripiprazole	Alpha-2C adrenergic receptor	Protein	Humans	No	Antagonist Other/unknown	Details
Aripiprazole	Dopamine D1 receptor	Protein	Humans	Unknown	Antagonist Partial agonist Ligand	Details
Aripiprazole	Dopamine D3 receptor	Protein	Humans	Unknown	Antagonist Partial agonist	Details
Aripiprazole	Dopamine D4 receptor	Protein	Humans	Unknown	Antagonist Partial agonist	Details
Aripiprazole	Dopamine D5 receptor	Protein	Humans	Unknown	Antagonist Partial agonist Ligand	Details
Aripiprazole	Histamine H1 receptor	Protein	Humans	No	Antagonist	Details
Aripiprazole lauroxil	5-hydroxytryptamine receptor 1B	Protein	Humans	Unknown	Not Available	Details
Aripiprazole lauroxil	5-hydroxytryptamine receptor 1D	Protein	Humans	Unknown	Not Available	Details
Aripiprazole lauroxil	5-hydroxytryptamine receptor 1E	Protein	Humans	Unknown	Not Available	Details
Aripiprazole lauroxil	5-hydroxytryptamine receptor 2C	Protein	Humans	Unknown	Not Available	Details
Aripiprazole lauroxil	5-hydroxytryptamine receptor 3A	Protein	Humans	Unknown	Not Available	Details
Aripiprazole lauroxil	5-hydroxytryptamine receptor 6	Protein	Humans	Unknown	Not Available	Details
Aripiprazole lauroxil	5-hydroxytryptamine receptor 7	Protein	Humans	Unknown	Not Available	Details
Aripiprazole lauroxil	Alpha-1A adrenergic receptor	Protein	Humans	No	Antagonist	Details
Aripiprazole lauroxil	Alpha-1B adrenergic receptor	Protein	Humans	No	Antagonist	Details
Aripiprazole lauroxil	Alpha-2A adrenergic receptor	Protein	Humans	No	Not Available	Details
Aripiprazole lauroxil	Alpha-2B adrenergic receptor	Protein	Humans	No	Not Available	Details
Aripiprazole lauroxil	Alpha-2C adrenergic receptor	Protein	Humans	No	Not Available	Details
Aripiprazole lauroxil	Dopamine D1 receptor	Protein	Humans	Unknown	Not Available	Details
Aripiprazole lauroxil	Dopamine D3 receptor	Protein	Humans	Unknown	Not Available	Details
Aripiprazole lauroxil	Dopamine D4 receptor	Protein	Humans	Unknown	Not Available	Details
Aripiprazole lauroxil	Dopamine D5 receptor	Protein	Humans	Unknown	Not Available	Details
Aripiprazole lauroxil	Histamine H1 receptor	Protein	Humans	No	Antagonist	Details
Aripiprazole lauroxil	Muscarinic acetylcholine receptor M1	Protein	Humans	No	Not Available	Details
Aripiprazole lauroxil	Muscarinic acetylcholine receptor M2	Protein	Humans	No	Not Available	Details
Aripiprazole lauroxil	Muscarinic acetylcholine receptor M3	Protein	Humans	No	Not Available	Details
Aripiprazole lauroxil	Muscarinic acetylcholine receptor M4	Protein	Humans	No	Not Available	Details
Aripiprazole lauroxil	Muscarinic acetylcholine receptor M5	Protein	Humans	No	Not Available	Details
Clozapine	5-hydroxytryptamine receptor 1B	Protein	Humans	Unknown	Antagonist	Details
Clozapine	5-hydroxytryptamine receptor 1D	Protein	Humans	Unknown	Antagonist	Details
Clozapine	5-hydroxytryptamine receptor 1E	Protein	Humans	Unknown	Antagonist	Details
Clozapine	5-hydroxytryptamine receptor 3A	Protein	Humans	Unknown	Antagonist	Details
Clozapine	5-hydroxytryptamine receptor 6	Protein	Humans	Unknown	Antagonist	Details
Clozapine	5-hydroxytryptamine receptor 7	Protein	Humans	Unknown	Antagonist	Details
Clozapine	Alpha-1A adrenergic receptor	Protein	Humans	Unknown	Antagonist	Details
Clozapine	Alpha-1B adrenergic receptor	Protein	Humans	No	Antagonist	Details
Clozapine	Alpha-2A adrenergic receptor	Protein	Humans	Unknown	Antagonist	Details
Clozapine	Alpha-2B adrenergic receptor	Protein	Humans	No	Antagonist	Details
Clozapine	Alpha-2C adrenergic receptor	Protein	Humans	No	Antagonist	Details
Clozapine	Dopamine D3 receptor	Protein	Humans	Unknown	Antagonist	Details
Clozapine	Muscarinic acetylcholine receptor M1	Protein	Humans	Unknown	Partial agonist	Details
Clozapine	Muscarinic acetylcholine receptor M2	Protein	Humans	Unknown	Partial agonist	Details
Clozapine	Muscarinic acetylcholine receptor M3	Protein	Humans	Unknown	Antagonist	Details
Clozapine	Muscarinic acetylcholine receptor M4	Protein	Humans	Unknown	Partial agonist	Details
Clozapine	Muscarinic acetylcholine receptor M5	Protein	Humans	Unknown	Antagonist	Details
奥氮平	5-hydroxytryptamine receptor 2A	Protein	Humans	Yes	Antagonist	Details
奥氮平	5-hydroxytryptamine receptor 3A	Protein	Humans	Unknown	Antagonist	Details
奥氮平	5-hydroxytryptamine receptor 6	Protein	Humans	Unknown	Antagonist	Details
奥氮平	Alpha-1A adrenergic receptor	Protein	Humans	Unknown	Antagonist	Details
奥氮平	Alpha-1B adrenergic receptor	Protein	Humans	Unknown	Antagonist	Details
奥氮平	Dopamine D1 receptor	Protein	Humans	Unknown	Antagonist	Details
奥氮平	Dopamine D2 receptor	Protein	Humans	Yes	Antagonist	Details
奥氮平	Dopamine D3 receptor	Protein	Humans	Unknown	Antagonist	Details
奥氮平	Dopamine D5 receptor	Protein	Humans	Unknown	Antagonist	Details
奥氮平	Muscarinic acetylcholine receptor M1	Protein	Humans	Unknown	Antagonist	Details
奥氮平	Muscarinic acetylcholine receptor M2	Protein	Humans	Unknown	Antagonist	Details
奥氮平	Muscarinic acetylcholine receptor M3	Protein	Humans	Unknown	Antagonist	Details
奥氮平	Muscarinic acetylcholine receptor M4	Protein	Humans	Unknown	Antagonist	Details
Quetiapine	5-hydroxytryptamine receptor 1A	Protein	Humans	Unknown	Antagonist Partial agonist	Details
Quetiapine	5-hydroxytryptamine receptor 1B	Protein	Humans	Unknown	Ligand	Details
Quetiapine	5-hydroxytryptamine receptor 1D	Protein	Humans	Unknown	Ligand	Details
Quetiapine	5-hydroxytryptamine receptor 1E	Protein	Humans	Unknown	Ligand	Details
Quetiapine	5-hydroxytryptamine receptor 2A	Protein	Humans	Yes	Antagonist	Details
Quetiapine	5-hydroxytryptamine receptor 2C	Protein	Humans	Unknown	Ligand	Details
Quetiapine	5-hydroxytryptamine receptor 3A	Protein	Humans	Unknown	Ligand	Details
Quetiapine	5-hydroxytryptamine receptor 6	Protein	Humans	Unknown	Antagonist	Details
Quetiapine	5-hydroxytryptamine receptor 7	Protein	Humans	Unknown	Ligand	Details
Quetiapine	Alpha-1 adrenergic receptors (Protein Group)	Protein group	Humans	Unknown	Antagonist	Details
Quetiapine	Alpha-2A adrenergic receptor	Protein	Humans	Unknown	Antagonist	Details
Quetiapine	Alpha-2B adrenergic receptor	Protein	Humans	Unknown	Antagonist	Details
Quetiapine	Alpha-2C adrenergic receptor	Protein	Humans	Unknown	Antagonist	Details
Quetiapine	Dopamine D1 receptor	Protein	Humans	Unknown	Antagonist	Details
Quetiapine	Dopamine D2 receptor	Protein	Humans	Yes	Antagonist	Details
Quetiapine	Dopamine D3 receptor	Protein	Humans	Unknown	Ligand	Details
Quetiapine	Dopamine D4 receptor	Protein	Humans	Unknown	Ligand	Details
Quetiapine	Dopamine D5 receptor	Protein	Humans	Unknown	Ligand	Details
Quetiapine	Histamine H1 receptor	Protein	Humans	Unknown	Antagonist	Details
Quetiapine	Muscarinic acetylcholine receptor M1	Protein	Humans	Unknown	Antagonist	Details
Quetiapine	Muscarinic acetylcholine receptor M2	Protein	Humans	Unknown	Ligand	Details
Quetiapine	Muscarinic acetylcholine receptor M3	Protein	Humans	Unknown	Antagonist	Details
Quetiapine	Muscarinic acetylcholine receptor M4	Protein	Humans	Unknown	Ligand	Details
Quetiapine	Muscarinic acetylcholine receptor M5	Protein	Humans	Unknown	Ligand	Details
Ziprasidone	5-hydroxytryptamine 3 receptor (Protein Group)	Protein group	Humans	Unknown	Antagonist	Details
Ziprasidone	5-hydroxytryptamine receptor 1B	Protein	Humans	Unknown	Antagonist	Details
Ziprasidone	5-hydroxytryptamine receptor 1E	Protein	Humans	Unknown	Antagonist	Details
Ziprasidone	5-hydroxytryptamine receptor 2A	Protein	Humans	Yes	Antagonist	Details
Ziprasidone	5-hydroxytryptamine receptor 5A	Protein	Humans	Unknown	Antagonist	Details
Ziprasidone	5-hydroxytryptamine receptor 6	Protein	Humans	Unknown	Antagonist	Details
Ziprasidone	5-hydroxytryptamine receptor 7	Protein	Humans	Unknown	Antagonist	Details
Ziprasidone	Alpha-1A adrenergic receptor	Protein	Humans	Unknown	Antagonist	Details
Ziprasidone	Alpha-1B adrenergic receptor	Protein	Humans	Unknown	Antagonist	Details
Ziprasidone	Alpha-2A adrenergic receptor	Protein	Humans	Unknown	Antagonist	Details
Ziprasidone	Alpha-2B adrenergic receptor	Protein	Humans	Unknown	Antagonist	Details
Ziprasidone	Alpha-2C adrenergic receptor	Protein	Humans	Unknown	Antagonist	Details
Ziprasidone	Dopamine D1 receptor	Protein	Humans	Unknown	Antagonist	Details
Ziprasidone	Dopamine D2 receptor	Protein	Humans	Yes	Antagonist	Details
Ziprasidone	Dopamine D3 receptor	Protein	Humans	Unknown	Antagonist	Details
Ziprasidone	Dopamine D4 receptor	Protein	Humans	Unknown	Antagonist	Details
Ziprasidone	Dopamine D5 receptor	Protein	Humans	Unknown	Antagonist	Details
Ziprasidone	Histamine H1 receptor	Protein	Humans	Unknown	Antagonist	Details
Ziprasidone	Muscarinic acetylcholine receptor M1	Protein	Humans	Unknown	Antagonist	Details
Ziprasidone	Muscarinic acetylcholine receptor M2	Protein	Humans	Unknown	Antagonist	Details
Ziprasidone	Muscarinic acetylcholine receptor M3	Protein	Humans	Unknown	Antagonist	Details
Ziprasidone	Muscarinic acetylcholine receptor M4	Protein	Humans	Unknown	Antagonist	Details
Ziprasidone	Muscarinic acetylcholine receptor M5	Protein	Humans	Unknown	Antagonist	Details

Drug InteractionsLearn More" title="" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">

Drugs	Interaction
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Clozapine Tropicamide	风险啊r severity of reduced gastrointestinal motility can be increased when Tropicamide is combined with Clozapine.
Clozapine Cyclopentolate	风险啊r severity of reduced gastrointestinal motility can be increased when Cyclopentolate is combined with Clozapine.
Clozapine Dihydro-2-thioxo-5-((5-(2-(trifluoromethyl)phenyl)-2-furanyl)methyl)-4,6(1H,5H)-pyrimidinedione	风险啊r severity of reduced gastrointestinal motility can be increased when Dihydro-2-thioxo-5-((5-(2-(trifluoromethyl)phenyl)-2-furanyl)methyl)-4,6(1H,5H)-pyrimidinedione is combined with Clozapine.
Clozapine Homatropine	风险啊r severity of reduced gastrointestinal motility can be increased when Homatropine is combined with Clozapine.
Clozapine Metixene	风险啊r severity of reduced gastrointestinal motility can be increased when Metixene is combined with Clozapine.
Clozapine Trihexyphenidyl	风险啊r severity of reduced gastrointestinal motility can be increased when Trihexyphenidyl is combined with Clozapine.
Clozapine Procyclidine	风险啊r severity of reduced gastrointestinal motility can be increased when Procyclidine is combined with Clozapine.
Clozapine Amantadine	风险啊r severity of reduced gastrointestinal motility can be increased when Amantadine is combined with Clozapine.
Clozapine Dexetimide	风险啊r severity of reduced gastrointestinal motility can be increased when Dexetimide is combined with Clozapine.
Clozapine Tropatepine	风险啊r severity of reduced gastrointestinal motility can be increased when Tropatepine is combined with Clozapine.

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