Mackay A V
J Clin Psychiatry. 1985 Apr;46(4 Pt 2):51-3.
In the absence of knowledge about the etiology of the diseases being treated and of adequate animal models, the future design of antipsychotic agents must rely largely on a pragmatic extension from the drugs already known to be useful. The property of dopamine receptor antagonism has proved a reliable predictor of antipsychotic effect. It may be argued that further therapeutic gains through development of more selective and more potent dopamine antagonists are unlikely. A general limitation of receptor-active drugs is the phenomenon of reactive change in receptor numbers. For long-term maintenance treatment, it may be sensible to search for a neuroleptic equivalent of lithium, which has no direct effect on membrane receptors. The two most pressing clinical issues are 1) persuading clinicians to use the minimum effective clinical dose for the shortest time, and 2) developing an effective treatment for the schizophrenic defect state, its possible association with cerebral atrophy notwithstanding.
在缺乏对所治疗疾病病因的了解以及合适动物模型的情况下，抗精神病药物的未来设计在很大程度上必须依赖于对已知有用药物的务实拓展。多巴胺受体拮抗特性已被证明是抗精神病作用的可靠预测指标。可能有人会说，通过开发更具选择性和更强效的多巴胺拮抗剂来进一步提高治疗效果不太可能。受体活性药物的一个普遍局限性是受体数量的反应性变化现象。对于长期维持治疗，寻找一种相当于锂盐的抗精神病药物可能是明智的，锂盐对膜受体没有直接作用。两个最紧迫的临床问题是：1）说服临床医生在最短时间内使用最低有效临床剂量；2）开发一种有效的治疗精神分裂症缺陷状态的方法，尽管它可能与脑萎缩有关。
