Brosda Jan, Jantschak Florian, Pertz Heinz H
Institute of Pharmacology and Toxicology, School of Veterinary Medicine, Freie Universität Berlin, 14195, Berlin, Germany.
Psychopharmacology (Berl). 2014 Mar;231(5):801-12. doi: 10.1007/s00213-014-3459-8. Epub 2014 Feb 2.
Almost all antipsychotic drugs (APDs), irrespective of whether they belong to the first-generation (e.g. haloperidol) or second-generation (e.g. clozapine), are dopamine D2 receptor antagonists. Second-generation APDs, which differ from first-generation APDs in possessing a lower propensity to induce extrapyramidal side effects, target a variety of monoamine receptors such as serotonin (5-hydroxytryptamine) receptors (e.g. 5-HT1A, 5-HT2A, 5-HT2C, 5-HT6, 5-HT7) and α1- and α2-adrenoceptors in addition to their antagonist effects at D2 receptors.
This short review is focussed on the potential role of α2-adrenoceptors in the antipsychotic therapy.
Schizophrenia is characterised by three categories of symptoms: positive symptoms, negative symptoms and cognitive deficits. α2-Adrenoceptors are classified into three distinct subtypes in mammals, α2A, α2B and α2C. Whereas the α2B-adrenoceptor seems to play only a minor role in the brain, activation of postsynaptic α2A-adrenoceptors in the prefrontal cortex improves cognitive functions. Preclinical models such as D-amphetamine-induced locomotion, the conditioned avoidance response and the pharmacological N-methyl-D-aspartate receptor hypofunction model have shown that α2C-adrenoceptor blockade or the combination of D2 receptor antagonists with idazoxan (α2A/2C-adrenoceptor antagonist) could be useful in schizophrenia. A potential benefit of a treatment combination of first-generation APDs with the α2A/2C-adrenoceptor antagonists idazoxan or mirtazapine was also demonstrated in patients with schizophrenia.
It is concluded that α2-adrenoceptors may be promising targets in the antipsychotic therapy.
几乎所有抗精神病药物（APD），无论其属于第一代（如氟哌啶醇）还是第二代（如氯氮平），都是多巴胺D2受体拮抗剂。第二代APD与第一代APD的不同之处在于，其诱发锥体外系副作用的倾向较低，除了对D2受体具有拮抗作用外，还作用于多种单胺受体，如5-羟色胺（5-羟色胺）受体（如5-HT1A、5-HT2A、5-HT2C、5-HT6、5-HT7）以及α1和α2肾上腺素能受体。
本简短综述聚焦于α2肾上腺素能受体在抗精神病治疗中的潜在作用。
精神分裂症具有三类症状：阳性症状、阴性症状和认知缺陷。α2肾上腺素能受体在哺乳动物中分为三种不同亚型，即α2A、α2B和α2C。虽然α2B肾上腺素能受体在大脑中似乎仅起次要作用，但前额叶皮质中突触后α2A肾上腺素能受体的激活可改善认知功能。临床前模型，如D-苯丙胺诱导的运动、条件性回避反应和药理学N-甲基-D-天冬氨酸受体功能减退模型表明，α2C肾上腺素能受体阻断或D2受体拮抗剂与咪唑克生（α2A/2C肾上腺素能受体拮抗剂）联合使用可能对精神分裂症有效。第一代APD与α2A/2C肾上腺素能受体拮抗剂咪唑克生或米氮平联合治疗对精神分裂症患者也显示出潜在益处。
得出结论，α2肾上腺素能受体可能是抗精神病治疗中很有前景的靶点。
