Clare College Cambridge, Cambridge, UK.
Psychiatr Danub. 2012 Sep;24 Suppl 1:S95-9.
Recently, the pharmacological division between typical and atypical antipsychotics has been called into question. New evidence, however, continues to emerge showing differences between these two classes of drugs. Hence typical and atypical antipsychotics are clearly different classes of drugs, as evidenced by their actions, mechanisms, effects and side effects. The most recently investigated field in which both classes of drugs have opposing effects is neuron survival and neurogenesis. Schizophrenia has been found to be a disease of progressive reductions in grey matter, and the more lost, the worse the outcome. Medication naive patients have lowered levels of neurotrophins e.g. NT-3, NGF BDNF. The antipsychotic drugs alter the levels of these neurotrophins. Haloperidol, of the typical antipsychotics, causes neuron apoptosis by a free radical induced mechanism, involving Bcl-XS, P53, cytochrome c translocation and caspase 3 activation. Haloperidol also lowers BDNF levels, reducing neuroprotection in the brain to enable haloperidol's toxic effects. Atypical drugs have opposing effects. They increase levels of BDNF, improve cell survival and enhance neurogenesis. Atypical drugs can also prevent or reverse the effects of haloperidol induced toxicity. The mechanism involves the inverse agonism of 5HT receptors, particularly those of the 2A subset, but the situation is considerably more complicated.
最近，典型和非典型抗精神病药物之间的药理学差异受到了质疑。然而，新的证据不断出现，表明这两类药物之间存在差异。因此，典型和非典型抗精神病药物显然是不同类别的药物，这可以从它们的作用、机制、效果和副作用中得到证明。最近研究的一个领域是这两类药物在神经元存活和神经发生方面的拮抗作用。精神分裂症已被发现是一种灰质进行性减少的疾病，丢失的越多，结果越差。未经药物治疗的患者神经生长因子（如 NT-3、NGF、BDNF）水平降低。抗精神病药物改变这些神经营养因子的水平。典型抗精神病药物氟哌啶醇通过自由基诱导的机制引起神经元凋亡，涉及 Bcl-XS、P53、细胞色素 c 易位和 caspase 3 激活。氟哌啶醇还降低了 BDNF 水平，减少了大脑中的神经保护作用，从而使氟哌啶醇产生毒性作用。非典型药物则有相反的作用。它们增加了 BDNF 的水平，提高了细胞的存活率，增强了神经发生。非典型药物还可以预防或逆转氟哌啶醇诱导的毒性作用。其机制涉及 5HT 受体的反向激动作用，特别是 2A 亚群的 5HT 受体，但情况要复杂得多。
