Costall B, Naylor R J
J Pharm Pharmacol. 1978 Nov;30(11):693-8. doi: 10.1111/j.2042-7158.1978.tb13367.x.
The activity spectra of oxiperomide, spiroxatrine and analogues were determined in two experimental models of abnormal peri-oral movements (induced by intrastriatal dopamine and subcutaneously administered 2-(NN-dipropyl)amino-5,6-dihydroxy-1,2,3,4-tetrahydronaphthalene (NN-diPr-5,6-diOHATN) in the guinea-pig), and in a stereotypy test (induced by subcutaneous apomorphine in the guinea-pig); the ability of the test compounds to induce catalepsy or catatonia in the rat was also determined. The parent compounds oxiperomide and spiroxatrine possessed optimal activity in all tests, although responses to the series of compounds allowed clear differentiation between an ability to antagonize the peri-oral movements (dopamine- or NN-di Pr-5,6-diOHATN induced) and an ability to antagonize apomorphine stereotypy. However, all compounds that antagonized the abnormal peri-oral movements also caused catalepsy/catatonia. The results are considered in terms of the selection of suitable agent(s) for the treatment of peri-oral dyskinesias.
在两种异常口周运动的实验模型（豚鼠纹状体内注射多巴胺和皮下注射2-(N,N-二丙基)氨基-5,6-二羟基-1,2,3,4-四氢萘（N,N-二丙基-5,6-二羟基-1,2,3,4-四氢萘）诱导）以及刻板行为测试（豚鼠皮下注射阿扑吗啡诱导）中测定了奥氮平、螺沙群及其类似物的活性谱；还测定了受试化合物诱导大鼠僵住症或紧张症的能力。尽管对该系列化合物的反应使得拮抗口周运动（多巴胺或N,N-二丙基-5,6-二羟基-1,2,3,4-四氢萘诱导）的能力与拮抗阿扑吗啡刻板行为的能力之间有明显区分，但母体化合物奥氮平和螺沙群在所有测试中均具有最佳活性。然而，所有拮抗异常口周运动的化合物也会引起僵住症/紧张症。从选择合适的药物治疗口周运动障碍的角度对结果进行了考量。
