Neduva A A, Zharkovskiĭ A M, Matvienko O A, Beliakov A V
Zh Nevropatol Psikhiatr Im S S Korsakova. 1985;85(8):1226-31.
To study the possible mechanisms of the formation of secondary therapeutic resistance, the author carried out a chronic experiment on animals which were administered different doses of a neuroleptic (haloperidol) for 20 days. The neuroleptic effect of the drug was shown to significantly decrease following prolonged administration. It was found that upon the first administration of haloperidol mice developed marked catalepsy 2 hours after administration. In conditions of a prolonged administration of the drug its cataleptogenic action was observed to diminish by the 20th day. Diminution of catalepsy was explained by a decrease of the blocking effect of the neuroleptic on the dopamine system. Change in the function of dopamine receptors (zigzag administration of haloperidol or administration of the drug simultaneously with apomorphine) was found to restore the cataleptogenic properties of the neuroleptic. The data obtained were used in the treatment of 47 patients with paranoid schizophrenia who developed resistance to pharmacotherapy.
为研究继发性治疗抵抗形成的可能机制，作者对动物进行了一项慢性实验，给动物连续20天给予不同剂量的抗精神病药（氟哌啶醇）。结果显示，长期给药后该药物的抗精神病作用显著降低。发现首次给予氟哌啶醇后，小鼠在给药2小时后出现明显的僵住症。在长期给药的情况下，到第20天时观察到其致僵住症作用减弱。僵住症的减轻被解释为抗精神病药对多巴胺系统的阻断作用降低。发现多巴胺受体功能的改变（氟哌啶醇的曲折给药或与阿扑吗啡同时给药）可恢复抗精神病药的致僵住症特性。所获得的数据被用于治疗47例对药物治疗产生抵抗的偏执型精神分裂症患者。
