可乐定对慢性神经病理性痛大鼠背根神经节GAP-43 mRNA表达的影响

目的 探讨可乐定对慢性神经病理性痛大鼠生长相关蛋白(GAP-43)mRNA表达的影响.方法 雄性成年SD大鼠36只,体重180～220 g,随机分为假手术组(S组)、慢性压迫性损伤组(CCI组)和可乐定组(CL组),每组12只.采用结扎坐骨神经法制备慢性压迫性损伤模型,S组仅暴露坐骨神经,不结扎.CL组于坐骨神经结扎术后3～14 d每天腹腔注射可乐定1 mg/kg.S组和CCI组腹腔注射生理盐水1 ml.于术前、术后3、7、14 d时测定机械痛阈和热痛阈,术后3、7、14 d测定痛阈后随机取4只大鼠断头处死,取腰段脊髓(L_(4～6))及背根神经节,采用RT-PCR法检测GAP-43 mRNA的表达水平.结果 与S组比较,CCI组和CL组术后机械痛阈和热痛阈降低,背根神经节GAP-43 mRNA表达上调(P<0.05);与CCI组比较,CL组术后7、14 d时机械痛阈和热痛阈升高,背根神经节GAP-43 mRNA表达下调(P<0.05).结论 坐骨神经结扎术后3～14 d每天腹腔注射可乐定1 mg/kg可有效减轻大鼠慢性神经病理性痛,其机制可能与其抑制背根神经节GAP-43 mRNA表达上调有关.     

氯胺酮联合吗啡、可乐定用于晚期癌痛患者硬膜外自控镇痛

目的:探讨吗啡+氯胺酮+可乐定对晚期癌痛的自控镇痛效果。方法:60例三阶梯疗法欠佳的晚期癌症疼痛病人随机均分4组,分别配制吗啡、吗啡+氯胺酮、吗啡+可乐定、吗啡+氯胺酮+可乐定镇痛液进行硬膜外自控镇痛(PCEA),记录第1、3、6、10、15、17、20 d的视觉模拟评分(VAS),测量血压、脉搏、氧饱和度,并用汉密顿抑郁量表(HAMD)进行治疗前后的抑郁情绪评估,记录恶心、呕吐、尿潴留、皮肤瘙痒、呼吸抑制等并发症。结果:吗啡+氯胺酮+可乐定组VAS评分和HAMD评分均较其他3组低、不良反应次数最少。结论:吗啡+氯胺酮+可乐定用于晚期癌症镇痛效果好,副作用少,安全性高。     

The stimulatory effect of clonidine on locus coeruleus neurons of rats with inactivated α2-adrenoceptors: involvement of imidazoline receptors located in the nucleus paragigantocellularis

Clonidine stimulates locus coeruleus neurons by an α₂-adrenoceptor-independent mechanism which probably involves imidazoline receptors. To study this effect, single-unit extracellular recordings in the locus coeruleus were performed in anaesthetised rats after complete, irreversible inactivation of α₂-adrenoceptors by the alkylating agent N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) (6 mg/kg i.p.; 6 h before experiments). After this pretreatment, clonidine applied into the locus coeruleus failed to produce any change in the cell firing rate. However, clonidine applied intravenously (320–2560 μg/kg), or locally (0.5–2.0 μl of 0.02 M) into the nucleus paragigantocellularis, a major locus coeruleus afferent, stimulated locus coeruleus neurons (increasing the firing rate by approximately 90%). Electrical lesions of the nucleus paragigantocellularis greatly attenuated the clonidine induced stimulation of locus coeruleus neurons ipsilateral to the lesion when applied intravenously. Blood pressure which was recorded simultaneously with cell recording, remained unaffected after clonidine administration in EEDQ pretreated rats. These results indicate that the clonidine-induced stimulation of locus coeruleus neurons is an indirect effect mediated by imidazoline receptors located on paragigantocellularis neurons projecting to the locus coeruleus. Received: 12 August 1996 / Accepted: 13 October 1996     

Randomised double-blind comparison of lofexidine and clonidine in the out-patient treatment of opiate withdrawal

This study compares the clinical response to lofexidine and clonidine in the out-patient treatment of opiate withdrawal in 50 opiate addicts, using a randomised double-blind study design. Patients were taking 40 mg or less methadone daily, or equivalent amounts of other opiates. Fifty-eight percent of those starting treatment completed detoxification, and were opiate free at 4 weeks: more patients completed withdrawal in the lofexidine group, but the difference was not significant. Clonidine produced more hypotensive effects: more home visits were also required by medical staff. There was no other significant difference in side effects. Both drugs can be used successfully in out-patient detoxification, but lofexidine is more economical in regard to staff time.     

Clonidine- and Methohexital-Induced Epileptiform Discharges Detected by Magnetoencephalography (MEG) in Patients with Localization-Related Epilepsies

Summary: Purpose: During presurgical evaluation, 14 patients with medically intractable focal epilepsies underwent magnetoencephalographic (MEG) recordings to localize the epileptogenic focus. To increase the number of epileptiform discharges required for MEG analysis, methohexital a short-acting barbiturate that is known to activate epileptiform activity, was used. Additionally, we investigated the spike-provoking properties of clonidine in comparison to methohexital. Methods: After oral premedication with clonidine, short-lasting anesthesia was provided by intravenously administered methohexital. The number and location of epileptiform MEG discharges were assessed after clonidine premedication and during methohexital anesthesia. Results were compared with baseline MEG recordings. Results: Methohexital increased the frequency of focal epileptiform discharges in eight of 13 patients (one of the 14 patients did not receive methohexital after premedication with clonidine). Additionally, premedication with clonidine was found to increase focal epileptiform discharges in nine of 14 patients. When compared with baseline MEG recordings, recordings after treatment with both clonidine premedication and methohexital anesthesia showed a significant increase in the total number of epileptiform signals and the number of spikes contributing to MEG source localizations. Conclusions: This study confirms the selective proconvulsant effects of methohexital on the epileptogenic focus as suggested previously by EEG and electrocorticogram (ECoG) investigations. Additionally, our data establish for the first time that clonidine increases epileptiform activity in patients with seizure disorders. These results indicate that clonidine is suited as an activating agent for the localization of epileptogenic foci by means of MEG. This effect of clonidine on specific epileptic activity also indicates that clonidine should be used with caution as an antihypertensive drug in patients with seizure disorders.     

Pharmacologically evoked fictive motor patterns in the acutely spinalized marmoset monkey (Callithrix jacchus)

The existence of a spinal network capable of generating rhythmic alternating activity resembling locomotion still has not been firmly established in primates, including man, although evidence for one is accumulating. The present study investigated whether it is possible to activate such a network by administration of a variety of pharmacological agents to acutely spinalized marmoset monkeys (Callithrix jacchus) in the absence of phasic afferent input to the spinal cord. Fourteen marmoset monkeys were decerebrated, spinalized, and paralyzed. The nerves supplying both hindlimbs were cut and recorded from. In 5 monkeys the effect of electrical stimulation of the brainstem was investigated before spinalization. In 3 of these monkeys, rhythmic activity alternating between extensors and flexor nerves was seen. In the 2 other monkeys only synchronized activity was elicited. In acutely spinalized monkeys, administration of l-3,4-dihydroxyphenylalanine (l-dopa; 3–4 h after treatment with nialamide) failed to evoke any rhythmic alternating activity. In contrast, administration of clonidine elicited alternating activity in all of 8 monkeys tested. In 4 of these monkeys, the activity was restricted to alternation between ipsilateral and contralateral flexor nerves, whereas alternating activity between ipsilateral flexors and extensors was also seen in the other 4 monkeys. Administration of excitatory amino acids (NMDA or NMA) also elicited rhythmic alternating activity in 7 of 10 spinalized monkeys. In 4, rhythmic alternating activity was seen between extensors and flexors on one limb as well as between ipsilateral and contralateral flexors. In 3 monkeys NMDA/NMA produced alternation between extensors and flexors of one limb without alternation between the ipsilateral and contralateral sides. Administration of noradrenaline failed to elicit any rhythmic activity, but rather completely depressed already existing activity. Administration of serotonin (5-HT) was ineffective in facilitating alternating activity in 6 of 8 monkeys and was facilitatory to rhythmic activity in the other 2. We suggest that these data provide further evidence of a network capable of eliciting rhythmic alternating activity resembling locomotion in the primate spinal cord. The network, however, seems to be more difficult to activate pharmacologically in those conditions than in other mammals. This may especially be the case in higher primates, including man. Received: 6 November 1997 / Accepted: 21 April 1998     

高分子药物－可乐定阴离子丙烯酸树脂盐的研制及释药性能探索

研制了高分子药物－可乐定阴离子丙烯酸树脂盐并在模拟胃和小肠ｐＨ的缓冲液中进行了高分子药物的溶解释放试验。结果表明其中某些试样能够在微碱性的缓冲液中缓慢溶解释放，可望达到减少用药量。降低副作用和延长药效的目的。     

Synergistic effect of growth hormone-releasing hormone (GHRH) and clonidine in stimulating GH release in young and old dogs

The effect of acute administration of growth hormone-releasing hormone (GHRH), clonidine (CLO), an alleged GHRH releaser, or GHRH and clonidine given simultaneously was studied in young and old dogs. Simultaneous administration of CLO induced in young dogs an additive effect on GH release and potentiated in old dogs the GHRH-induced GH release, with the GH response being clearly higher than the sum of the GH responses to GHRH or CLO alone. These data suggest that CLO promotes GH release in the dog also by inhibition of somatostatin release.     

不同处理方法对全麻手术病人气管拔管应激反应的影响

目的探讨不同处理方法对全麻病人术后气管拔管应激反应的影响。方法44例气管插管全麻下手术病人,随机分为四组(n=11):对照组(N组)、可乐定组(K组)、硬膜外组(EP组)、可乐定复合硬膜外组(KEP组)。除K组和KEP组病人分别于麻醉前60min口服可乐定5 uuuuuuuuuuuuuuuuuuug/kg外,四组病人其它麻醉前用药相同;分别在麻醉前、拔管前、拔管后1、2、5、10 min经桡动脉采集动脉血7 ml, 测定血浆肾上腺素、去甲肾上腺素(NE)、皮质醇、血糖、血乳酸浓度,并做血气分析,同时记录以上各时点的血液动力学参数。结果与拔管前比较,N组、EP组拔管后1min HR、SBP、DBP升高,拔管后2 min SBP、DBP仍较高;与N组比较,K、EP、KEP组病人拔管后1 min肾上腺素、NE、皮质醇水平均较低, 拔管后2、5min K组、KEP组血浆激素水平较低,K组、KEP组拔管前、拔管后1、2min血乳酸水平较低, 拔管后1、2min血糖水平较低,K组、KEP组拔管后1、2 min HR、SBP、DBP较低(P<0.05或0.01)。与N组比较,K、EP、KEP组病人拔管后1 min血肾上腺素、NE、皮质醇水平均较低,拔管后2、5 min K组、KEP组血浆激素水平较低(P<0.05或0.01)。与N组比较,K组、KEP组拔管前、拔管后1、2min血乳酸升高程度较低;拔管后1、2min血糖升高程度较低(P<0.05或0.01)。N组、EP组拔管后1 min HR、SBP、DBP比拔管前升高,拔管后2 min SBP、DBP仍较高;K组、KEP组拔管后1、2min HR、SBP、DBP较N 组低(P<0.05或0.01)。结论全麻病人麻醉前服用可乐定或拔管时复合硬膜外给药能明显减轻气管拔管引起的应激反应。