抗精神病药物与毒蕈碱剂对中枢多巴胺能系统的相互作用。
The interaction of neuroleptic and muscarinic agents with central dopaminergic systems.
作者信息
Kelly P H, Miller R J
出版信息
Br J Pharmacol. 1975 May;54(1):115-21. doi: 10.1111/j.1476-5381.1975.tb07417.x.
Abstract
- The effect of muscarinic and neuroleptic agents on the turning behaviour induced by methamphetamine and apomorphine in rats with unilateral lesions of the substantia nigra induced by 6-hydroxydopamine has been examined. 2. Turning towards the side of the lesion induced by (+)-methamphetamine (5 mg/kg) was inhibited by alpha-flupenthixol (1 mg/kg) and alpha-clopenthixol (8 mg/kg) but not by high doses of their beta-isomers. 3. Turning was inhibited by chlorpromazine (4 mg/kg) and pimozide (0.2 mg/kg). Thioridazine and clozapine (16 mg/kg) were ineffective. Turning in the same direction produced by scopolamine (10 mg/kg) was also inhibited by alpha-flupenthixol (1 mg/kg) and pimozide (0.25 mg/kg). 4. Turning produced by methamphetamine (5 mg/kg) was inhibited by oxotremorine (0.75 mg/kg) even in the presence of methylatropine (5 mg/kg). 5. Turning away from the side of the lesion induced by apomorphine (0.1 mg/kg) was inhibited by oxotremorine (0.75 mg/kg) but not by thioridazine or clozapine (16 mg/kg). 6. These results are discussed with regard to the mode of action of neuroleptic drugs in producing anti-psychotic effects and drug-induced Parkinsonism.
摘要
- 已研究了毒蕈碱能药物和抗精神病药物对6-羟基多巴胺诱导的黑质单侧损伤大鼠中甲基苯丙胺和阿扑吗啡所致旋转行为的影响。2. （+）-甲基苯丙胺（5毫克/千克）诱导的向损伤侧旋转受到氟哌噻吨（1毫克/千克）和氯哌噻吨（8毫克/千克）的抑制，但高剂量的β-异构体则无此作用。3. 氯丙嗪（4毫克/千克）和匹莫齐特（0.2毫克/千克）可抑制旋转。硫利达嗪和氯氮平（16毫克/千克）无效。东莨菪碱（10毫克/千克）产生的同一方向的旋转也受到氟哌噻吨（1毫克/千克）和匹莫齐特（0.25毫克/千克）的抑制。4. 即使存在甲基阿托品（5毫克/千克），奥曲肽（0.75毫克/千克）仍可抑制甲基苯丙胺（5毫克/千克）所致的旋转。5. 奥曲肽（0.75毫克/千克）可抑制阿扑吗啡（0.1毫克/千克）诱导的远离损伤侧的旋转，但硫利达嗪或氯氮平（16毫克/千克）则无此作用。6. 就抗精神病药物产生抗精神病作用和药物性帕金森综合征的作用方式对这些结果进行了讨论。
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