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Dopamine-cell depolarization block as a model for the therapeutic actions of antipsychotic drugs.

机译:多巴胺细胞去极化阻滞作为抗精神病药治疗作用的模型。

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摘要

Antipsychotic drugs used in the treatment of schizophrenia have in common the property of being dopamine-receptor antagonists. However, the rapid timecourse of receptor blockade produced upon drug administration does not correlate with the emergence of clinical actions, which typically require weeks of treatment to become manifest. Studies in rats have shown that repeated antipsychotic drug treatment results in a delayed inactivation of dopamine-neuron firing in the midbrain due to depolarization block. Furthermore, the therapeutic efficacy of antipsychotic drugs in humans correlates with their ability to induce depolarization block of mesolimbic dopamine neurons, whereas their potential to produce extrapyramidal side effects correlates with their propensity for inducing depolarization block in the nigrostriatal dopamine system. Therefore, dopamine-cell depolarization block is an effective model for evaluating antipsychotic drug efficacy, and provides a potential mechanism to account for their therapeutic impact on a dysregulated dopamine system.
机译:用于治疗精神分裂症的抗精神病药具有作为多巴胺受体拮抗剂的特性。然而,药物给药后产生的受体阻断的快速过程与临床作用的出现无关,临床作用的出现通常需要数周的治疗才能显现出来。对大鼠的研究表明,由于去极化阻滞,反复进行抗精神病药物治疗会导致中脑中多巴胺神经元放电延迟失活。此外,抗精神病药对人的治疗功效与其诱导中脑边缘多巴胺神经元去极化阻断的能力有关,而它们产生锥体束外副作用的潜力与其在黑质纹状体多巴胺系统中诱导去极化阻断的倾向有关。因此,多巴胺细胞去极化阻滞是评估抗精神病药疗效的有效模型,并提供了一种潜在的机制来解释其对失调的多巴胺系统的治疗作用。

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