Clonidine Induces Sedation Through Acting on the Perifornical Area and the Locus Coeruleus in Rats

Sakamoto, Hidetoshi; Fukuda, Satoru; Minakawa, Yoichi; Sawamura, Shigehito

doi:10.1097/ana.0b013e3182978ff0

Cited by 15 publications

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“…This action is responsible for a decrease in anxiety, tremors, weakness, heart rate and hypertension after ethanol withdrawal. Furthermore, the sedative properties associated with CLN that are mediated through attenuation of NA and acetylcholine fluxes in LC and perifornical areas of brain could contribute in the management of EWS . However, while a few contradictory studies have reported anxiogenic effects at higher doses , we did not observe any anxiogenic effects that CLN might have during our study.…”

Section: Discussioncontrasting

confidence: 71%

Comparative Evaluation of Partial α₂‐Adrenoceptor Agonist and Pure α₂‐Adrenoceptor Antagonist on the Behavioural Symptoms of Withdrawal after Chronic Alcohol Administration in Mice

Arora

Vohora

2016

Basic Clin Pharma Tox

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As an addictive drug, alcohol produces withdrawal symptoms if discontinued abruptly after chronic use. Clonidine (CLN), a partial a 2 -adrenergic agonist, and mirtazapine (MRT), an antagonist of a 2 -adrenoceptor, both clinically aid alcohol withdrawal. Considering different mechanisms of action of the two drugs, this study was designed to see how far these two mechanistically different drugs differ in their ability to decrease the severity of ethanol withdrawal syndrome. The effect of CLN and MRT on ethanol withdrawal-induced anxiety, depression and memory impairment was analysed using EPM, FST and PAR tests, respectively. Animals received distilled water, ethanol and/or either of the drugs (CLN and MRT) in different doses. Relapse to alcohol use was analysed by CPP test. Animals received ethanol as a conditioning drug and distilled water, CLN or MRT as test drug. CLN and MRT both alleviated anxiety in a dose-dependent manner. MRT (4 mg/kg) was more effective than CLN (0.1 mg/kg) in ameliorating the anxiogenic effect of alcohol withdrawal. However, CLN treatment increased depression. It significantly decreased swimming time and increased immobility time, whereas MRT treatment decreased immobility time and increased climbing and swimming time during abstinence. The effect was dose dependent for both drugs. The results of PAR test show that CLN treatment worsens working memory. Significant increase in SDE and TSZ and decrease in SDL were observed in CLN-treated animals. MRT treatment, on the other hand, improved working memory at both doses. Further, both CLN and MRT alleviated craving. A significant decrease in time spent in the ethanol-paired chamber was seen. MRT treatment at both doses showed better effect than CLN in preventing the development of preference in CPP test. These findings indicate a potential therapeutic use and better profile of mirtazapine over clonidine in improving memory, as well as in alleviating depression, anxiety and craving associated with alcohol withdrawal.Drug addiction is a pathological state which involves the progression of acute drug use to the development of drugseeking behaviour, vulnerability to relapse and decreased ability to respond to naturally rewarding stimuli [1,2]. The abused drugs produce an extensive and wide range of effects on the structure and networking of nerve cells throughout the brain's reward circuitry. These changes are believed to underlie the long-lasting behavioural changes which are characteristic of addiction [3]. Amongst all the drugs of abuse, alcohol is one of the most frequently abused. Chronic overuse of alcohol damages brain cells and its neuro-toxic potential has made it amongst the leading causes of dementia worldwide. Epidemiological studies report a significant association between alcohol and comorbid anxiety and depressive disorders [4]. Abstinence from long-term ethanol consumption induces an increase in negative emotional responses such as feelings of anxiety, restlessness, hyper-irritability, and depressed mood [5,6].Autonomic ...

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Section: Discussioncontrasting

confidence: 71%

Comparative Evaluation of Partial α₂‐Adrenoceptor Agonist and Pure α₂‐Adrenoceptor Antagonist on the Behavioural Symptoms of Withdrawal after Chronic Alcohol Administration in Mice

Arora

Vohora

2016

Basic Clin Pharma Tox

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“…The temperature of the chambers were servo controlled to maintain chamber temperature between 31–33°C and three different dosages of morphine (2, 10 and 20 mg/kg) and clonidine (40, 200 and 400μg/kg) were used. While these doses were selected based on previous publications that demonstrated neuroprotection and/or temperature modulation (Ammon-Treiber et al 2004, Hoffman et al 1991, Yuan et al 2001), the range for analgesic-sedative dose in rats is 1–24mg/kg for morphine (Kawaraguchi et al 2008, McLaughlin et al 1990) and 50–1000 μg/kg for clonidine (Sakamoto et al 2013, Skingle et al 1982). …”

Section: Methodsmentioning

confidence: 99%

Breathing and temperature control disrupted by morphine and stabilized by clonidine in neonatal rats

Kesavan

Ezell

Bierman

et al. 2014

Respiratory Physiology & Neurobiology

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Background Sedative-analgesics are often given to newborn infants and are known to affect many components of the autonomic nervous system. While morphine is most frequently used, α-2 adrenergic receptor agonists are being increasingly used in this population. Alpha-2 adrenergic receptors agonists also have anti-shivering properties which may make it a desirable drug to give to infants undergoing therapeutic hypothermia. The aim of this study was to systematically compare two different classes of sedative-analgesics, morphine, a μ-opioid receptor agonist, and clonidine an α-2 adrenergic receptor agonist on breathing, metabolism and core body temperature (CBT) in neonatal rodents. Methods Breathing parameters, oxygen consumption (VO2) and carbon dioxide production (VCO2), were measured prior to, 10 and 90 minutes after intraperitoneal (IP) administration of morphine (2, 10 or 20mg/kg), clonidine (40, 200 or 400 μg/kg), or saline in Sprague-Dawley rat pups at postnatal day 7 (p7) while continuously monitoring CBT. Results Morphine reduced the respiratory rate, VO2 and VCO2 greater than clonidine at all dosages used (p<0.05, morphine vs. clonidine, for all metabolic and respiratory parameters). Furthermore, morphine induced prolonged respiratory pauses, which were not observed in animals treated with clonidine or saline. Morphine caused hypothermia which was dose dependent, while clonidine stabilized CBT in comparison to saline treated animals (p<0.0001). Conclusion In the newborn rat, morphine causes profound respiratory depression and hypothermia while clonidine causes minimal respiratory depression and stabilizes CBT. All together, we suggest that clonidine promotes autonomic stability and may be a desirable agent to use in infants being treated with therapeutic hypothermia.

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“…Postoperative pain scores (VAS) were significantly lower in patients who had taken oral clonidine, compared to patients who were sedated using midazolam. Clonidine has partly alpha 2 agonist effects, which, through central nervous system (locus cereleus ( 8 ) and spinothalamic pathways ( 9 ), provides some sort of analgesic effects. The alpha 2 adrenoceptor is highly enriched in the spinal dorsal horn and involved in descending noradrenergic pain modification ( 10 ).…”

Section: Discussionmentioning

confidence: 99%

Preemptive Oral Clonidine Provides Better Sedation Than Intravenous Midazolam in Brachial Plexus Nerve Blocks

et al. 2016

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BackgroundPreemptive analgesia is the blocking of pain perception afferent pathways before noxious painful stimuli. Clonidine is an alpha agonist drug that is partially selective for α-2 adrenoreceptors. Clonidine is used as anti-anxiety medication and an, analgesic, and it prolongs the duration of the block in the brachial plexus block.ObjectivesTo compare the effect of preemptive clonidine with midazolam on intraoperative sedation, duration of block, and postoperative pain scores.Patients and MethodsIn a randomized clinical trial, 80 patients with orthopedic fractures of an upper extremity who underwent supraclavicular nerve block were randomly assigned to receive 0.2 mg oral clonidine or 2 mg oral midazolam. Intraoperative sedation was measured at one hour after the start of urgery and again in the PACU (Post-Anesthesia Care Unit) using the Ramsay scale. The duration of sensory blockade was measured. Postoperative pain scores were measured using the VAS (Visual Analogue Scale) after entrance to recovery up to 2 hours.ResultsThe percentages of patients in the calm and sedated scale were significantly higher in clonidine group (35 and 42.5%, respectively), compared to the midazolam group (17.5 and 17.5%, respectively) (P = 0.042, 0.029; respectively). Those administered fentanyl in the clonidine group 105 ± 30.8 was significantly lower than that for the midazolam group 165 ± 34.5 (P = 0.0018). The percentages of patients in the calm scale were significantly higher in the clonidine group (52.5), compared to the midazolam group (17.5) (P = 0.001) in the post-operative period. VAS scores were significantly lower at one (P = 0.01) and two hours (P = 0.001) after operation in the clonidine group, compared to the midazolam group.ConclusionsPreemptive clonidine has many marvelous advantages over midazolam, including better sedation inside the operating room and then in the post-operative care unit, lower fentanyl doses are required during surgery, more stable heart rate and blood pressure are observed during the procedure, and patients report lower post-operative pain scores.

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Clonidine Induces Sedation Through Acting on the Perifornical Area and the Locus Coeruleus in Rats

Abstract: The Pef and the LC are responsible for the sedative action of CLO in rats.

Cited by 15 publications

References 0 publications

Comparative Evaluation of Partial α₂‐Adrenoceptor Agonist and Pure α₂‐Adrenoceptor Antagonist on the Behavioural Symptoms of Withdrawal after Chronic Alcohol Administration in Mice

Comparative Evaluation of Partial α₂‐Adrenoceptor Agonist and Pure α₂‐Adrenoceptor Antagonist on the Behavioural Symptoms of Withdrawal after Chronic Alcohol Administration in Mice

Breathing and temperature control disrupted by morphine and stabilized by clonidine in neonatal rats

Preemptive Oral Clonidine Provides Better Sedation Than Intravenous Midazolam in Brachial Plexus Nerve Blocks

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Clonidine Induces Sedation Through Acting on the Perifornical Area and the Locus Coeruleus in Rats

Abstract: The Pef and the LC are responsible for the sedative action of CLO in rats.

Cited by 15 publications

References 0 publications

Comparative Evaluation of Partial α2‐Adrenoceptor Agonist and Pure α2‐Adrenoceptor Antagonist on the Behavioural Symptoms of Withdrawal after Chronic Alcohol Administration in Mice

Comparative Evaluation of Partial α2‐Adrenoceptor Agonist and Pure α2‐Adrenoceptor Antagonist on the Behavioural Symptoms of Withdrawal after Chronic Alcohol Administration in Mice

Breathing and temperature control disrupted by morphine and stabilized by clonidine in neonatal rats

Preemptive Oral Clonidine Provides Better Sedation Than Intravenous Midazolam in Brachial Plexus Nerve Blocks

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Comparative Evaluation of Partial α₂‐Adrenoceptor Agonist and Pure α₂‐Adrenoceptor Antagonist on the Behavioural Symptoms of Withdrawal after Chronic Alcohol Administration in Mice

Comparative Evaluation of Partial α₂‐Adrenoceptor Agonist and Pure α₂‐Adrenoceptor Antagonist on the Behavioural Symptoms of Withdrawal after Chronic Alcohol Administration in Mice