Clozapine and olanzapine, but not haloperidol, reverse cold-induced and lipopolysaccharide-induced cutaneous vasoconstriction
Clozapine and olanzapine, but not haloperidol, reverse cold-induced and lipopolysaccharide-induced cutaneous vasoconstriction
复制标题
氯氮平和奥氮平可逆转寒冷诱导和脂多糖诱导的皮肤血管收缩，但氟哌啶醇无效
作者：
W. Blessing
体温下降被用作精神药物作用的预测指标。皮肤循环作为温度调节的热损失组分起作用。氯氮平和奥氮平逆转MDMA诱导的体温过高和交感神经介导的皮肤血管收缩（3，4-亚甲二氧基甲基苯丙胺、摇头丸），目的比较氯氮平和奥氮平与氟哌啶醇逆转冷诱导和LPS诱导的血管收缩的能力，（脂多糖）诱导的兔皮肤血管收缩in the rabbit. Methodsskinblood flow was measured in conscious rabbit by Doppler ultrasound flow probe implanted around the central ear artery，and body temperature was measured telemetrically.对照观察后，将动物从26 ° C转移至10°C，或给予LPS（0.5 μg/kg IV）。30分钟后，氯氮平，奥氮平或氟哌啶醇管理和耳廓血流量和体温测量另一个30分钟。Results氯氮平，在剂量反应的方式（1，2.5和5毫克/公斤IV），基本上逆转冷诱导耳廓血管收缩和降低体温。氯氮平（1 mg/kg IV）可逆转LPS诱导的皮肤血管收缩，并降低LPS诱导的体温升高。奥氮平的作用基本相似。氟哌啶醇（1毫克/千克IV在寒冷的实验和0.2毫克/千克IV在LPS实验）没有扭转耳廓血管收缩，或影响body temperature. Conclusions氯氮平和奥氮平，但不是氟哌啶醇，扭转生理诱导的皮肤交感神经血管放电。由于心理功能与交感神经对皮肤血流的调节密切相关，因此非典型抗精神病药物的皮肤血管舒张作用和精神作用可能具有相似的神经药理学机制。
RationaleReduction of body temperature is used as predictor of psychotropic drug action. The cutaneous circulation functions as a heat-loss component of temperature regulation. Clozapine and olanzapine reverse hyperthermia and sympathetically-mediated cutaneous vasoconstriction induced by MDMA (3,4-methylenedioxymethamphetamine, ecstasy), suggesting that these drugs might reverse other forms of sympathetically mediated cutaneous vasoconstriction.ObjectivesClozapine and olanzapine were compared with haloperidol with respect to their ability to reverse cold-induced and LPS (lipopolysaccharide)-induced cutaneous vasoconstriction in rabbits.MethodsCutaneous blood flow was measured in conscious rabbits by Doppler ultrasonic flow probe implanted around the central ear artery, and body temperature was measured telemetrically. After control observations, animals were transferred from 26 to 10°C, or LPS (0.5 μg/kg IV) was administered. After 30 min, clozapine, olanzapine or haloperidol was administered and ear pinna blood flow and body temperature were measured for another 30 min.ResultsClozapine, in a dose responsive manner (1, 2.5 and 5 mg/kg IV), substantially reversed cold-induced ear pinna vasoconstriction and reduced body temperature. Clozapine (1 mg/kg IV) reversed LPS-induced cutaneous vasoconstriction and reduced the LPS-induced rise in body temperature. Olanzapine had generally similar effects. Haloperidol (1 mg/kg IV in cold experiments and 0.2 mg/kg IV in LPS experiments) did not reverse ear pinna vasoconstriction, or affect body temperature.ConclusionsBoth clozapine and olanzapine, but not haloperidol, reverse physiologically induced cutaneous sympathetic vasomotor discharge. Because of the close link between psychological function and sympathetic regulation of cutaneous blood flow, similar neuropharmacological mechanisms might underly the cutaneous vasodilating action and the psychotropic actions of atypical antipsychotic drugs.
DOI：
--
发表时间：
2001-10
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
D. Weiner;E. Burstein;N. Nash;G. Croston;E. Currier;K. Vanover;S. C. Harvey;E. Donohue;H. Hansen;M. AnderssonCarl;T. Spalding;D. Gibson;K. Krebs-Thomson;S. Powell;M. Geyer;U. Hacksell;M. Brann
通讯作者：
D. Weiner;E. Burstein;N. Nash;G. Croston;E. Currier;K. Vanover;S. C. Harvey;E. Donohue;H. Hansen;M. AnderssonCarl;T. Spalding;D. Gibson;K. Krebs-Thomson;S. Powell;M. Geyer;U. Hacksell;M. Brann
DOI：
10.1176/jnp.1.3.253
发表时间：
1989
期刊：
The Journal of neuropsychiatry and clinical neurosciences
影响因子：
--
作者：
Peroutka,SJ;Sleight,AJ;McCarthy,BG;Pierce,PA;Schmidt,AW;Hekmatpanah,CR
通讯作者：
Hekmatpanah,CR
非典型精神安定药对大鼠血清素受体介导的神经内分泌和温度反应的拮抗作用。
影响因子：
5
作者：
Nash,JF;Meltzer,HY;Gudelsky,GA
通讯作者：
Gudelsky,GA