BACKGROUND/AIMS: DA-9701 is a novel prokinetic agent. In the present study, we investigated the effect of DA-9701 on the motility of the gastric antrum in the normal and clonidine-induced hypomotility in an in vivo animal model. METHODS: A strain gauge force transducer was sutured on the gastric antrum to measure the contractile activity in rats. A total of 28 rats were subclassified into the 4 groups: (1) the placebo group, (2) the DA-9701 group, (3) the placebo group in the clonidine-pretreated rats, and (4) the DA-9701 group in the clonidine-pretreated rats. After the basal recording, either placebo (3% [w/v] hydroxypropylmethyl cellulose) or DA-9701 was administered. Contractile signals were measured after the administration and after a meal. In the clonidine-pretreated rats, either placebo or DA-9701 was administered. Contractile signals were measured after the administration and after a meal. RESULTS: Oral administration of DA-9701 did not significantly alter the motility index of the gastric antrum in the preprandial and postprandial periods, compared with the placebo group. The administration of clonidine decreased the motility index of the gastric antrum in the preprandial and postprandial periods, compared with the administration of placebo. This reduction of the antral motility by the administration of clonidine was not observed in the clonidine-pretreated DA-9701 group. The percentage of the motility index in the postprandial period was significantly greater in the clonidine-pretreated DA-9701 group, compared with the clonidine-pretreated placebo group. CONCLUSIONS: DA-9701 improves the hypomotility of the gastric antrum induced by clonidine, suggesting its gastroprokinetic effect in the pathologic condition.
Administration, Oral ; Animals ; Clonidine ; Meals ; Models, Animal ; Postprandial Period ; Pyloric Antrum* ; Rats* ; Transducers

AIMTo determine clonidine in rabbit plasma by LC-MS.

METHODSThe LC-MS system consisted of Waters Alliance 2790 HPLC and Micromass ZQ-4000 MS. The HPLC was performed by using XTerra C18 (150 mm x 2.1 mm ID, 5 microm). The mobile phase, consisting of acetonitrile/ammonium hydrogen carbonate solution, was maintained to a flow-rate of 0.2 mL x min(-1) and the linear gradient elution was adopted. Mass spectrum was obtained by using electrospray ionization interface and the m/z of SIM was 230.

RESULTSThe average recovery was high and the method was reproducible. The calibration curve showed good linearity in the range of 1 - 80 microg x L(-1), the lowest limit of detection was 0.05 microg x L(-1). The Cmax, AUC0-t, and Tmax value of the pharmacokinetics parameter were (27 +/- 9) microg x L(-1), (5,352 +/- 1,121) microg x L(-1), (79 +/- 17) h.

CONCLUSIONThe results demonstrated that the method had high sensitivity, good selectivity, accuracy and precision. It is used to determine the clonidine concentration in plasma. The transdermal patch can deliver clonidine to the surface of rabbit skin stably for periods of up to 1 week after a single application.

Administration, Cutaneous ; Animals ; Antihypertensive Agents ; administration & dosage ; blood ; pharmacokinetics ; Area Under Curve ; Chromatography, High Pressure Liquid ; methods ; Clonidine ; administration & dosage ; blood ; pharmacokinetics ; Rabbits ; Spectrometry, Mass, Electrospray Ionization ; methods

OBJECTIVETo investigate the effects of intrathecal ouabain and tizanidine injection for treatment of neuropathic pain in rats.

METHODSMale SD rats weighing 250-300 g were randomly divided into 5 groups (n = 6), namely the control group, ouabain group, tizanidine group, combined ouabain and tizanidine injection group, and the antagonist group. Intrathecal catheter was implanted 7 days before spinal nerve ligation to establish the neuropathic pain model. Mechanical withdrawal threshold (MWT) before and after intrathecal administration of the agents was recorded in the rats. Isobolographic analysis was performed to evaluate the interactions between the agents.

RESULTSIntrathecal injection of ouabain (0.25-5 microg) or tizanidine (0.5-5 microg) alone produced dose-dependent analgesic effect against the neuropathic pain (P < 0.05). Isobolographic analysis revealed a synergistic interaction between ouabain and tizanidine. Intrathecal pretreatment with atropine (5 microg) or yohimbine (20 microg) antagonized the effects of ouabain and tizanidine administered alone or in combination (P < 0.05).

CONCLUSIONIntathecal injection of ouabain or tizanidine produces dose-dependent analgesic effects against neuropathic pain, and their synergistic effect after combined injection probably involves the cholinergic transmission and alpha2 receptor.

Analgesics ; administration & dosage ; Animals ; Clonidine ; administration & dosage ; analogs & derivatives ; Injections, Spinal ; Ouabain ; administration & dosage ; Pain ; drug therapy ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Spinal Nerves ; injuries

Administration, Cutaneous ; Adolescent ; Antihypertensive Agents ; administration & dosage ; therapeutic use ; Child ; Clonidine ; administration & dosage ; therapeutic use ; Double-Blind Method ; Female ; Humans ; Male ; Tic Disorders ; drug therapy

OBJECTIVETo investigate the effects of intrathecal escin and clonidine, used alone or in combination, in the treatment of neuropathic pain in rats and the possible mechanism.

METHODSNinety-six male SD rats weighing 250-300 g were chronically implanted with lumbar intrathecal catheters. One week later, the left L5 and L6 spinal nerve roots were ligated to establish the model of spinal nerve ligation neuropathic pain (SNL). The rats were then randomly divided into 16 groups (n=6), including the control (saline), escin, clonidine, escin+clonidine, and the antagonist groups. Mechanical withdrawal threshold was assessed before and at 5, 10, 20, 30, 40, 50 and 60 min after intrathecal administration was evaluated. The maximal possible effect (MPE) was calculated and the effect of the treatments on the neuropathic pain. Isobolographic analysis was performed to characterize any potential interactions between the drugs.

RESULTSMPE was significantly higher in escin group (20, 40 microg), clonidine group (2, 5, 10 microg) and escin+clonidine group [1/4, 1/2 (escin ED(50)+clonidine ED(50))] than in the saline group (P<0.05). Intrathecal escin (5-40 microg) or clonidine (1-10 microg) alone dose-dependently alleviated neuropathic pain. Isobolographic analysis suggested a synergistic effect between escin and clonidine. Intrathecal pretreatment with yohimbine (20 microg) antagonized the effects of clonidine (P<0.01) and attenuated the action of the combination treatment with escin and clonidine (P<0.05).

CONCLUSIONIntrathecal escin and clonidine alone can dose-dependently relieve neuropathic pain. Escin and clonidine produce a synergistic effect for pain relief, which may involve the actions of alpha(2) receptor and Ca(2+) channel.

Analgesics ; administration & dosage ; Animals ; Clonidine ; administration & dosage ; Drug Synergism ; Escin ; administration & dosage ; Injections, Spinal ; Male ; Pain ; drug therapy ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Spinal Nerve Roots ; injuries

OBJECTIVEChildren with Tourette's syndrome (TS) have a poor treatment compliance due to side effects and inconvenient administration of oral drugs. This study explored the efficacy and safety of clonidine transdermal patch for treating TS in children.

METHODSA total of 119 children with TS were randomly treated with the clonidine transdermal patch (n=65) or with oral haloperidol (n=54). The therapeutic efficacy was assessed based on the results of the Yale Global Tic Severity Scale (YGTSS) 4 weeks after treatment.

RESULTSThe clonidine transdermal patch group showed a higher reduction in the overall tic symptom scores (61.5+/-7.5%) than that in the haloperidol group (41.0+/-6.3%; p<0.05). Clonidine transdermal patch treatment was effective in 53 patients (81.5%) and 36 patients (67.5%) showed effective to oral haloperidol (p>0.05). Mild side effects (decrease of blood pressure and dizziness) were observed in 1 patient in the clonidine transdermal patch group. Mild hypermyotonia, drowsiness or lassitude as side effects occurred in 6 patients in the haloperidol group.

CONCLUSIONSClonidine transdermal patch is effective for the treatment of TS in children and its side effects are mild and rare.

Administration, Cutaneous ; Adolescent ; Child ; Child, Preschool ; Clonidine ; administration & dosage ; adverse effects ; pharmacology ; Female ; Haloperidol ; therapeutic use ; Humans ; Male ; Tourette Syndrome ; drug therapy

Increases in heart rate (HR) and blood pressure (BP) are common during light planes of anesthesia at the end of operation and just prior to extubation. This study was undertaken to investigate and compare HR and BP responses to endotracheal extubation during light general anesthesia with and without prior intravenous administration of clonidine. Eighty hypertensive patients aged 45-65 yr were undergoing a variety of operations. In this study, the BP of hypertensive patients was well controlled on antihypertensive regimens before anesthesia. Anesthesia was induced by the injection of thiopental sodium, diazepam, fentanyl and vecuronium, and maintained with enflurane (0.8-2.5 per cent) and nitrous oxide (50 per cent) in oxygen. Patients were randomly divided into two groups of 40 each with regard to management of endotracheal extubation at the end of operation. Patients in clonidine group received an izv injection of clonidine (0.75 ug/kg) 30 min. prior to extubation. One minute prior to extubation, baseline arterial BP and HR were recoreded. Single measurement of systolic and diastolic BP and HR were obtained during the study and were recorded at 30 seconds, 1 min., 2 min., 3 min., 4 min. and 5 min. after extubation, and upon entrance to the postanesthetic recovery room (6-10 min. after extubation). Patients in control group received no injection prior to extubation, but were otherwise treated similarly and had data recorded at the same times as those in clonidine group. The results were as follows ;1) No significant differences were noted in BP and HR prior to clonidine administration between patients in the two groups. 2) Thirty seconds after extubation, both BP and HR increased significantly in both group (p< 0.05) but the increasing rate in clonidine group was significantly less than in control group (p<0.05). 3) Patients in control and clonidine group sustained a significant elevation in both BP and HR which persisted for 3 and 1 min after extubation (p<0.05), respectively. 4) Changes in both BP and HR in patients of clonidine group became significantly less than control group every time intervals after extubation (p<0.05). In conclusion, the result of this study demonstrate that iv injection of clonidine (0.75 ug/kg) administered 30 min. before endotracheal extubation prevents increases in BP and HR before and after extubation and in the recovery room. The data suggest that iv clonidine injection prior to extubation should be of advantage to patients with hypertension who may not be able to tolerate the increased hemodynamics which usually accompany endotracheal extubation.
Administration, Intravenous ; Airway Extubation ; Anesthesia ; Anesthesia, General ; Blood Pressure ; Clonidine* ; Diazepam ; Enflurane ; Fentanyl ; Heart Rate ; Hemodynamics ; Humans ; Hypertension ; Nitrous Oxide ; Oxygen ; Recovery Room ; Thiopental ; Vecuronium Bromide

BACKGROUND: Clonidine, alpha2-adrenoreceptor agonist, has nonopiate antinociceptive properties, which might be an alternative for postoperative analgesia free of opioid induced side effects. The aim of this study was to evaluate the fentanyl sparing effect of clonidine and reducing side effects with intravenous administration. METHODS: Fourty seven patients undergoing a cesarean section were randomly allocated to two groups to be given the following agents by intravenous administration. Group I, fentanyl 0.2ng/kg/h with clonidine 0.2ng/kg/h for 72 h adding normal saline for a total of 150 cc. Group II, fentanyl 0.4ng/kg/h for 72 h adding normal saline for a total of 150 cc and analgesia was provided intravenously via patient -controlled analgesia (PCA; basal rate = 2 ml, rescure dose = 1 ml, lock-out time = 10 min). Postoperative analgesia was assessed by VAS at 2, 4, 8, and 24 h after extubation. In addition, we also checked the vital sign sedation score. RESULTS: There were no differences of VAS scores, hemodynamic values except systolic pressure (P < 0.05), or side effects between group I and group II. The frequency of nausea was 8.7% in group I and 29% in group II, and dizziness was 4.3% in group I and 8.3% in group II. CONCLUSIONS: Intravenous clonidine with narcotics is a possible approach to postoperative pain management in patients recovering from major surgery, especially spine surgery, and clonidine spares and reduces side effects in narcotics.
Administration, Intravenous ; Analgesia ; Blood Pressure ; Cesarean Section* ; Clonidine* ; Dizziness ; Female ; Fentanyl* ; Hemodynamics ; Humans ; Infusions, Intravenous* ; Narcotics ; Nausea ; Pain, Postoperative ; Pregnancy ; Spine ; Vital Signs

The central dopaminergic receptor is believed to suppress the cardiovascular system So it may be involved in the blood pressure regulation But, it's action is still controversial. Furthermore, the mechanisms involved in the central dopaminergic receptor-induced blood pressure regulation is unclear. So, present study was performed in order to clarify the effects of central dopaminergic receptor and to investigate the mechamisms involved in it. Lisuride a D2-receptor agonist, and clonidine, a alpha2-receptor agonist, were administered into lateral ventricle in rat and the changes of blood pressure were compared The results were as follows; 1. Intracerebroventricular administration of lisuride amd clonidine from 0.3 ug to 10 ug elicited dose related decrease of blood pressure and heart rate. The potencies were similar in both drugs. 2. Centrally administered sulpiride, a D2-antagonist, blocked only the lisuride-induced hypotension while the clonidine induced hypotension was blocked only by centrally adrninistered tolazoline, a alpha2-antagonist. Intravenous administration of both antagonists elicited no or minimal attenuabon of agonists effects. 3. After desipramine pretreatment, which increases the norepinephrine concentration lisuride elicited somewhat further decrease of blood pressure than normal, while clonidine administration caused rather increase in blood pressure. 4. After chemical sympathectomy by 6-hydroxydopamine, lisuride administration still elicited strong suppression of blood pressure. From thses above results, it is concluded that central dopaminergic receptor activation decrease the blood pressure. Suppression of the norepinephrine release at the sympathetic nerve terminal is not related with central dopaminergic receptor induced hypotension.
Administration, Intravenous ; Animals ; Blood Pressure ; Cardiovascular System* ; Clonidine ; Desipramine ; Heart Rate ; Hypotension ; Lateral Ventricles ; Lisuride ; Norepinephrine ; Oxidopamine ; Rats ; Sulpiride ; Sympathectomy, Chemical ; Tolazoline

OBJECTIVETo investigate the difference in the efficacy between clonidine transdermal patch and haloperidol tablets in the treatment of moderate to severe tic disorders in children.

METHODSA total of 134 children with moderate to severe tic disorders were randomly divided into clonidine group (n=70) and haloperidol group (n=64). The clonidine and haloperidol groups were treated with clonidine transdermal patch and haloperidol tablets respectively, and the treatment lasted for 8 weeks in both groups. The Yale Global Tic Severity Scale (YGTSS) was used to evaluate the conditions of the children before and after treatment, and the adverse events during the treatment were recorded.

RESULTSThe haloperidol group had a significantly better treatment outcome than the clonidine group after one week of treatment (P<0.05); the treatment outcome showed no significant difference between the two groups after 3, 5, and 8 weeks of treatment (P>0.05). The clonidine group had significantly less reductions in the motor tics, vocal tics, and function impairment scores and total score of YGTSS than the haloperidol group after one week of treatment (P<0.05); there were no significant differences in YGTSS score reductions between the two groups after 3, 5, and 8 weeks of treatment (P>0.05). The clonidine group had a significantly lower overall incidence of adverse events than the haloperidol group (8% vs 37%; P<0.01).

CONCLUSIONSClonidine transdermal patch and haloperidol are both effective in the treatment of moderate to severe tic disorders in children. The clonidine transdermal patch, despite slow action, has comparable efficacy and fewer adverse effects compared with haloperidol.

Child ; Child, Preschool ; Clonidine ; administration & dosage ; Female ; Haloperidol ; therapeutic use ; Humans ; Male ; Severity of Illness Index ; Tic Disorders ; drug therapy ; Transdermal Patch