The 5-HT2A receptor antagonist M100907 is more effective in counteracting NMDA antagonist than dopamine agonist induced hyperactivity in mice
The 5-HT2A receptor antagonist M100907 is more effective in counteracting NMDA antagonist than dopamine agonist induced hyperactivity in mice
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DOI：
10.1007/s007020050144
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发表时间：
1999-01-01
影响因子：
3.3
通讯作者：
Waters, N
中科院分区：
文献类型：
--
作者：
Carlsson, ML;Martin, P;Waters, N
本研究的目的是比较选择性5-HT 2A拮抗剂M100907在不同精神病模型中的有效性。使用经典的神经抑制剂氟哌啶醇作为参照化合物。使用两种多巴胺能亢进和两种多巴胺能减退小鼠模型。多巴胺能亢进症是由DA受体阻断剂d-苯丙胺或DA摄取抑制剂GBR 12909产生的。用非竞争性NMDA受体拮抗剂MK-801或竞争性NMDA受体拮抗剂D-CPPene产生低血压。发现M100907可抵消NMDA受体拮抗剂MK-801和D-CPPene的运动刺激作用，但对自发运动、d-苯丙胺和GBR-12909诱导的活动过度无显著影响。氟哌啶醇，另一方面，拮抗NMDA拮抗剂和DA激动剂诱导的多动症，以及自发运动在最高剂量使用。根据目前和以前的结果，我们得出的结论是，5-HT 2A受体拮抗剂是特别有效的对行为异常所造成的各种来源的hypocalamatergia。我们的研究结果和结论的临床意义是，5-HT 2A受体拮抗剂，由于其低副作用的倾向，可能是各种疾病的首选治疗策略与hypotheramatergia;这些条件可能包括精神分裂症。儿童自闭症和痴呆症。
The purpose of the present study was to compare the effectiveness of the selective 5-HT2A antagonist M100907 in different psychosis models. The classical neuroleptic haloperidol was used as reference compound. Two hyperdopaminergia and two hypoglutamatergia mouse models were used. Hyperdopaminergia was produced by the DA releaser d-amphetamine or the DA uptake inhibitor GBR 12909. Hypoglutamatergia was produced by the un-competitive NMDA receptor antagonist MK-801 or the competitive NMDA receptor antagonist D-CPPene. M100907 was found to counteract the locomotor stimulant effects of the NMDA receptor antagonists MK-801 and D-CPPene, but spontaneous locomotion, d-amphetamine- and GBR-12909-induced hyperactivity were not significantly affected. Haloperidol, on the other hand, antagonized both NMDA antagonist- and DA agonist-induced hyperactivity, as well as spontaneous locomotion in the highest dose used. Based on the present and previous results we draw the conclusion that 5-HT2A receptor antagonists are particularly effective against behavioural anomalies resulting from hypoglutamatergia of various origins. The clinical implications of our results and conclusions would be that a 5-HT2A receptor antagonist, due to i a the low side effect liability, could be the preferable treatment strategy in various disorders associated with hypoglutamatergia; such conditions might include schizophrenia. childhood autism and dementia disorders.