2017-10-17中枢神经系统药理2PDAD抗精神病药.ppt.ppt

* * 治疗初期即可使用，较少引发由于长期运用左旋多巴治疗所致的病情反复与运动障碍。 用左旋多巴无效的患者应用多巴胺激动剂. 溴隐亭:不良反应多 普拉克索：与左旋多巴联合用于PD重症治疗 * * * The neurotoxicity of MPTP was hinted at in 1976 after Barry Kidston, a 23-year-old chemistry graduate student in Maryland, US, synthesized MPPP with MPTP as a major impurity, and self-injected the result. Within three days he began exhibiting symptoms of Parkinsons disease. The National Institute of Mental Health found traces of MPTP and other pethidine analogs in his lab. They tested the substances on rats, but due to rodents tolerance for this type of neurotoxin nothing was observed. Kidstons Parkinsonism was treated with levodopa but he died 18 months later from a cocaine overdose. Upon autopsy, destruction of dopaminergic neurons in the substantia nigra was discovered.[6] In 1982, six people in Santa Clara County, California, US, were diagnosed with Parkinsonism after having used MPPP contaminated with MPTP. The neurologist J. William Langston in collaboration with NIH tracked down MPTP as the cause, and its effects on primates were researched. The motor symptoms of two of the seven patients were eventually successfully treated at Lund University Hospital in Sweden with neural grafts of fetal tissue.[7] * * * * 阿米替林：伴失眠的抑郁症患者 氯丙咪嗪：强迫症的首选药 * biogenic amine：生物胺 Hyperpyrexia： * * 对5-HT再摄取的抑制作用选择性强，对其他递质和受体作用甚微。 对抑郁症的疗效与三环类的相当，但安全性高于三环类 * 20世纪90年代初开发研制的，同时抑制5-HT,NE；而对肾上腺素能受体，胆碱能受体，组胺受体无亲和力。 * Noradrenergic and specific serotonergic antidepressant NA和特异性5-HT能抗抑郁药：阻断突触前膜的a2受体，削弱递质释放的抑制作用，使释放增加； NA释放增加后，激活5-HT神经元的a1受体，减弱5-HT1的抑制作用，使5-HT释放进一步增加， 但特异性阻断突触后膜5-HT2A, 5-HT2C and 5-HT3 比SSRIs起效快，安全，耐受性好；适用于各种抑郁症 * * * * 高效价/低剂量：锥体外系作用明显 低效价/高剂量：锥体外系副作用较轻 * 1.黑质-纹状体通路：各种原因减弱该通路的DA功能，可导致帕金森病，反之，出现多动症（D1，D5，D2，D4） 2.调控情绪反应；3.参与认知、思想、感觉、理解和推理能力的调控；I型精神分裂症与这2个通路的DA功能亢进密切相关。(D2，D3，D4) 4.主要调控垂体激素分泌（D2） B. Antimanic Drugs 1. Pharmacological effects and clinical uses Mood-stabilizing agent (1) Inhibiting NE and DA release (2) Interfering phosphatidylinositol (PI) metabolism (