p‐Chloroamphetamine‐induced hyperthermia pharmacologically distinct from fenfluramine‐induced hyperthermia
p‐Chloroamphetamine‐induced hyperthermia pharmacologically distinct from fenfluramine‐induced hyperthermia
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对氯苯丙胺引起的高热在药理学上不同于芬氟拉明引起的高热
DOI：
10.1111/j.2042-7158.1979.tb13416.x
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发表时间：
1979
影响因子：
3.3
通讯作者：
B. G. Weick
中科院分区：
文献类型：
--
作者：
R. Quock;B. G. Weick
研究了各种药物预处理对家兔对推定的间接5-羟色胺能激动剂对氯苯丙胺（PCA）和芬氟拉明反应的影响。在幼稚兔PCA引起体温过高，行为兴奋和突出的前爪阵挛活动，而芬氟拉明只产生体温过高和行为刺激。5-羟色胺（5-HT）摄取抑制剂氟西汀可降低两种药物的体温过高和行为反应，单胺氧化酶抑制剂非尼哌嗪可增强该反应，多巴胺能拮抗剂氟哌啶醇未改变该反应。用5-羟色胺能受体阻断剂桂南色林、赛庚啶或D-2-溴麦角酰二乙胺预处理可显著减弱芬氟拉明的作用，但仅轻微影响PCA的反应。用对氯苯丙氨酸去除中央5-HT储存也影响了对芬氟拉明的反应，而不是对PCA的反应。色胺能受体阻断剂甲麦角林消除了PCA诱导的体温过高和前爪阵挛，但没有行为刺激，而芬氟拉明的作用仅部分减少。我们将这些数据解释为PCA和芬氟拉明诱导的药物作用具有不同的潜在机制，PCA反应可能依赖于色胺，而芬氟拉明反应是5-羟色胺能的。
The influence of various drug pretreatments upon the responses of rabbits to the putative indirect 5‐hydroxytryptamincrgic agonists p‐chloroamphetamine (PCA) and fenfluramine were examined. In naive rabbits PCA evoked hyperthermia, behavioural excitation and prominent forepaw clonic activity, while fenfluramine produced only hyperthermia and behavioural stimulation. The hyperthermic and behavioural responses of both agents were reduced by the 5‐hydroxytryptamine (5‐HT) uptake inhibitor, fluoxetine, potentiated by the monoamine oxidase inhibitor, pheniprazine, and unaltered by the dopaminergic antagonist, haloperidol. Pretreatment with the 5‐hydroxytryptaminergic receptor blockers cinanserin, cyproheptadine or D‐2‐bromolysergic acid diethylamide markedly attenuated the effects of fenfluramine but only slightly influenced the responses to PCA. Depeletion of central 5‐HT stores with p‐chlorophenylalanine also affected responses to fenfluramine more than responses to PCA. The tryptaminergic receptor blocker methergoline abolished both PCA‐induced hyperthermia and forepaw clonus‐but not behavioural stimulation—while the effects of fenfluramine were only partly reduced. We interpret these data to mean that PCA‐ and fenfluramine‐induced drug effects have different underlying mechanisms, the PCA responses relying possibly upon tryptamine while the fenfluramine responses are 5‐hydroxytryptaminergic.