Institute of Pharmacology and Toxicology, School of Veterinary Medicine, Freie Universität Berlin, 14195, Berlin, Germany.
Institute of Pharmacy, Freie Universität Berlin, 14195, Berlin, Germany.
Psychopharmacology (Berl). 2018 Jan;235(1):99-108. doi: 10.1007/s00213-017-4747-x. Epub 2017 Oct 3.
2-Bromoterguride, a dopamine D receptor partial agonist with antagonist properties at serotonin 5-HT receptors and α-adrenoceptors, meets the prerequisites of a putative atypical antipsychotic drug (APD). We recently showed that 2-bromoterguride is effective in tests of positive symptoms of schizophrenia in rats without inducing extrapyramidal side effects or metabolic changes.
In continuation of our recent work, we now investigated the effect of 2-bromoterguride on apomorphine and phencyclidine (PCP)-induced disruptions of prepulse inhibition (PPI) of the acoustic startle response, a measure of sensory gating. In addition, we used subchronic PCP treatment to produce cognitive deficits and social aversion, and assessed the effect of 2-bromoterguride on the performance in the novel object recognition (NOR) task (model for studying cognitive deficit symptoms of schizophrenia) and the social interaction test (model for studying negative symptoms of schizophrenia). Finally, we extended the side effect profile of 2-bromoterguride by measuring the prolactin response to systemic administration of the drug in rats.
Treatment with 2-bromoterguride (0.1 and 0.3 mg/kg) reversed PPI deficits induced by apomorphine and PCP, respectively. Subchronic PCP induced impairments in object memory and social interaction behavior which were ameliorated by 2-bromoterguride but not by clozapine and aripiprazole, respectively. Prolactin concentration in blood serum was not elevated at 1, 2, or 4 h post-2-bromoterguride treatment, which further supports the safe and effective use of this drug.
Our data support 2-bromoterguride as a promising APD candidate due to its beneficial effect on cognitive impairments and negative symptoms of schizophrenia.
2-溴麦角隐亭，一种多巴胺 D 受体部分激动剂，对 5-羟色胺 5-HT 受体和α-肾上腺素受体具有拮抗剂特性，符合潜在的非典型抗精神病药物（APD）的先决条件。我们最近表明，2-溴麦角隐亭在大鼠的精神分裂症阳性症状测试中有效，而不会引起锥体外系副作用或代谢变化。
继我们最近的工作之后，我们现在研究了 2-溴麦角隐亭对阿扑吗啡和苯环己哌啶（PCP）诱导的听觉惊跳反应（一种感觉门控的测量）的预脉冲抑制（PPI）破坏的影响。此外，我们使用亚慢性 PCP 处理来产生认知缺陷和社交回避，并评估 2-溴麦角隐亭对新颖物体识别（NOR）任务（用于研究精神分裂症认知缺陷症状的模型）和社交互动测试（用于研究精神分裂症阴性症状的模型）的性能的影响。最后，我们通过测量药物在大鼠体内给药后的催乳素反应，扩展了 2-溴麦角隐亭的副作用谱。
2-溴麦角隐亭（0.1 和 0.3mg/kg）治疗分别逆转了阿扑吗啡和 PCP 诱导的 PPI 缺陷。亚慢性 PCP 引起物体记忆和社交互动行为受损，而 2-溴麦角隐亭改善了这些行为，但氯氮平或阿立哌唑则没有。2-溴麦角隐亭治疗后 1、2 或 4 小时，血清中的催乳素浓度没有升高，这进一步支持了该药物的安全有效使用。
我们的数据支持 2-溴麦角隐亭作为一种有前途的 APD 候选药物，因为它对精神分裂症的认知障碍和阴性症状有有益的作用。
