Witkin J, Gasior M, Acri J, Beekman M, Thurkauf A, Yuan J, DeBoer P, Wikström H, Dijkstra D
Drug Development Group, NIDA Addiction Research Center, NIH, Baltimore, MD 21224, USA.
Eur J Pharmacol. 1998 Apr 24;347(2-3):R1-3. doi: 10.1016/s0014-2999(98)00174-5.
Anti-schizophrenia agents with improved efficacy and side-effect profiles are required. A dopamine D3 receptor agonist, R-(+)-trans-3,4a,10b-tetrahydro-4-propyl-2H,5H-[1]benzopyrano[4,3- b]-1,4-oxazin-9-ol HCl ((+)-PD 128,907), displayed an atypical antipsychotic profile comparable to that of clozapine. (+)-PD 128,907 blocked stereotypy produced by dizocilpine (MK-801) at 12-fold lower doses than those affecting apomorphine-induced stereotypes in mice and did not produce catalepsy. These effects of (+)-PD 128,907 were stereospecific and were blocked by a D3 antagonist. These data suggest a role for D3 receptors in antipsychotic drug action.
需要具有更高疗效和更好副作用特征的抗精神分裂症药物。一种多巴胺D3受体激动剂，R-(+)-反式-3,4a,10b-四氢-4-丙基-2H,5H-[1]苯并吡喃并[4,3-b]-1,4-恶嗪-9-醇盐酸盐((+)-PD 128,907)，显示出与氯氮平相当的非典型抗精神病药物特征。(+)-PD 128,907在比影响阿扑吗啡诱导的刻板行为低12倍的剂量下就能阻断地佐环平(MK-801)产生的刻板行为，并且不会产生僵住症。(+)-PD 128,907的这些作用具有立体特异性，并且能被一种D3拮抗剂阻断。这些数据表明D3受体在抗精神病药物作用中发挥作用。
