Carlsson M L, Carlsson A, Nilsson M
Institute of Clinical Neuroscience, Neuropsychiatric Research Unit, Göteborg University, Sweden.
Curr Med Chem. 2004 Feb;11(3):267-77. doi: 10.2174/0929867043456034.
The first part of the present review describes the exciting journey of dopamine stabilizers, starting in the early eighties with the development of the partial dopamine agonist (-)-3-PPP of phenylpiperidine structure, via various compounds with aminotetraline structure with preferential autoreceptor antagonist properties, and then back again to phenylpiperidine compounds carrying substituents on the aromatic ring that transformed them from partial dopamine agonists to partial dopamine receptor antagonists, such as OSU6162. OSU6162 was brought to the clinic and has in preliminary trials showed antidyskinetic and antipsychotic efficacy. The second part of this review describes results from a hypoglutamatergia mouse model for cognitive symptoms of schizophrenia, where we have tested traditional neuroleptics, new generation antipsychotics with marked 5-HT2 vs dopamine D2 receptor blockade as well as a dopamine stabilizer belonging to the partial dopamine receptor antagonist category.
本综述的第一部分描述了多巴胺稳定剂令人兴奋的发展历程，始于八十年代初苯基哌啶结构的部分多巴胺激动剂（-）-3-PPP的研发，经过各种具有氨基四氢萘结构且具有优先自受体拮抗剂特性的化合物，然后又回到在芳环上带有取代基的苯基哌啶化合物，这些取代基将它们从部分多巴胺激动剂转变为部分多巴胺受体拮抗剂，如OSU6162。OSU6162已进入临床，初步试验显示其具有抗运动障碍和抗精神病疗效。本综述的第二部分描述了用于精神分裂症认知症状的低谷氨酸血症小鼠模型的研究结果，我们在该模型中测试了传统抗精神病药、具有显著5-HT2与多巴胺D2受体阻断作用的新一代抗精神病药以及一种属于部分多巴胺受体拮抗剂类别的多巴胺稳定剂。
