Clozapine increases cutaneous blood flow and reduces sympathetic cutaneous vasomotor alerting responses (SCVARs) in rats: comparison with effects of haloperidol
Clozapine increases cutaneous blood flow and reduces sympathetic cutaneous vasomotor alerting responses (SCVARs) in rats: comparison with effects of haloperidol
复制标题
氯氮平增加大鼠皮肤血流量并减少交感皮肤血管舒缩警报反应（SCVAR）：与氟哌啶醇的效果比较
作者：
W. Blessing
氯氮平抑制交感神经流出到皮肤血管床。氯氮平可逆转由3，4-亚甲二氧基甲基苯丙胺（MDMA，Ectamphetamine）或脂多糖（LPS）引起的体温过高和皮肤血管收缩。氯氮平也能逆转暴露于寒冷引起的皮肤血管收缩。这些作用将氯氮平与氟哌啶醇区分开来。氯氮平还可以抑制交感神经皮肤血管紧张性警觉反应（SCVARs），即反映情绪/心理功能的血管收缩反应，这一特性也可以将氯氮平与氟哌啶醇区分开来。（5 HT 2A受体拮抗剂），8-OH-DPAT（5-HT 1A激动剂），L741，626（多巴胺D2拮抗剂）或SCH 23390（多巴胺D1拮抗剂）有氯氮平-方法记录清醒自由活动大鼠在警觉刺激前后尾动脉多普勒血流信号的平均水平和脉冲幅度结果氯氮平（0.0625-1.0 mg/kg，s.c.）剂量依赖性增加静息尾血流量。1 mg/kg给药后，SCVAR指数为18± 1%，而溶剂给药后为83±2%。SR 46349 B（0.01-1.0 mg/kg）和8-OH-DPAT（0.25 mg/kg）对皮肤血流量和SCVAR的影响相似，但效力较低。氟哌啶醇（0.005-0.5 mg/kg）和L741，626（1 mg/kg）对这些变量没有影响或影响很小。SCH 23390轻度抑制SCVARs.ConclusionsClozapine，但不是氟哌啶醇，增加静息皮肤血流量，减少SCVARs。对5-HT 2A受体的拮抗作用和对5-HT 1A受体的激动作用可能有助于这些作用。
RationaleClozapine inhibits sympathetic outflow to the cutaneous vascular bed. Clozapine reverses hyperthermia and cutaneous vasoconstriction induced by 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) or by lipopolysaccharide (LPS). Clozapine also reverses cutaneous vasoconstriction elicited by exposure to cold. These actions distinguish clozapine from haloperidol. Clozapine could also inhibit sympathetic cutaneous vasomotor alerting responses (SCVARs), vasoconstrictor episodes that reflect emotional/psychological function, and this property might also distinguish clozapine from haloperidol.ObjectivesExperiments in rats determined whether clozapine and haloperidol inhibit SCVARs, and whether SR46349B (a 5HT2A receptor antagonist), 8-OH-DPAT (a 5-HT1A agonist), L741,626 (a dopamine D2 antagonist) or SCH23390 (a dopamine D1 antagonist) have clozapine-like effects on SCVARs.MethodsMean level and pulse amplitude of the tail artery Doppler flow signal were recorded in conscious freely moving rats before and after alerting stimuli (e.g. tapping the cage), and expressed as a SCVAR index (fall to zero flow implies SCVAR index of 100%, no fall implies 0%).ResultsClozapine (0.0625–1.0 mg/kg, s.c.) dose-dependently increased resting tail blood flow. After 1 mg/kg, the SCVAR index was 18±1%, compared with 83±2% after vehicle. SR46349B (0.01–1.0 mg/kg) and 8-OH-DPAT (0.25 mg/kg) had similar but less potent effects on cutaneous blood flow and on SCVARs. Haloperidol (0.005–0.5 mg/kg) and L741,626 (1 mg/kg) had no or little effect on these variables. SCH23390 mildly inhibited SCVARs.ConclusionsClozapine, but not haloperidol, increases resting cutaneous blood flow and decreases SCVARs. Antagonism at 5-HT2A receptors and agonism at 5-HT1A receptors could contribute to these actions.
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
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