Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085631 (agitation)
 12,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serotonin syndrome, a condition with numerous clinical neurological manifestations, is the result of central serotonergic hyperstimulation. Features of the syndrome include mental status and behavioral changes (agitation, excitement, hypomania, obtundation), motor system involvement (myoclonus, hemiballismus, tremor, hyperreflexia, motor weakness, dysarthria, ataxia) and autonomic symptoms (fever, chills, diarrhea). Serotonin syndrome has been reported exclusively in patients on medications for psychiatric illness and Parkinsonism, despite the fact that the putative action of many antimigraine agents also involves the serotonin system. We herein report six patients with migraine who developed symptoms suggestive of the serotonin syndrome. Five were taking one or more serotomimetic agents for migraine prophylaxis (sertraline, paroxetine, lithium, imipramine, amitriptyline). In each case the symptoms and signs developed in close temporal proximity with use of a migraine abortive agent known to interact with serotonin receptors. In three instances the agent was subcutaneous sumatriptan and, in three, intravenous dihydroergotamine. In each instance the symptoms were transient and there was full recovery. With the ever increasing use of migraine medications active at serotonin receptor sites, cases of serotonin syndrome will likely occur more frequently. It is important that physicians treating migraine are aware of the serotonin syndrome and are able to recognize its varying presentations.
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PMID:Serotonin syndrome complicating migraine pharmacotherapy. 886 67

Pain, nausea and vomiting are frequently listed by patients as their most important perioperative concerns. With the change in emphasis from an inpatient to outpatient hospital and office-based medical/surgical environment, there has been increased interest in the 'big little problem' of postoperative nausea and vomiting (PONV). Currently, the overall incidence of PONV is estimated to be 25 to 30%, with severe, intractable PONV estimated to occur in approximately 0.18% of all patients undergoing surgery. PONV can lead to delayed postanaesthesia care unit (PACU) recovery room discharge and unanticipated hospital admission, thereby increasing medical costs. The aetiology and consequences of PONV are complex and multifactorial, with patient-, medical- and surgery-related factors. A thorough understanding of these factors, as well as the neuropharmacology of multiple emetic receptors [dopaminergic, muscarinic, cholinergic, opioid, histamine, serotonin (5-hydroxy-tryptamine; 5-HT)] and physiology [cranial nerves VIII (acoustic-vestibular), IX (glossopharyngeal) and X (vagus), gastrointestinal reflex] relating to PONV are necessary to most effectively manage PONV. Commonly used older, traditional antiemetics for PONV include the anticholinergics (scopolamine), phenothiazines (promethazine), antihistamines (diphenhydramine), butyrophenones (droperidol) and benzamides (metoclopramide). These antiemetics have adverse effects such as dry mouth, sedation, hypotension, extrapyramidal symptoms, dystonic effects and restlessness. The newest class of antiemetics used for the prevention and treatment of PONV are the serotonin receptor antagonists (ondansetron, granisetron, tropisetron, dolasetron). These antiemetics do not have the adverse effects of the older, traditional antiemetics. Headache and dizziness are the main adverse effects of the serotonin receptor antagonists in the dosages used for PONV. The serotonin receptor antagonists have improved antiemetic effectiveness but are not as completely efficacious for PONV as they are for chemotherapy-induced nausea and vomiting. Older, traditional antiemetics (such as droperidol) compare favourably with the serotonin receptor antagonists regarding efficacy for PONV prevention. Combination antiemetic therapy improves efficacy for PONV prevention and treatment. In the difficult-to-treat PONV patient (as in the chemotherapy patient), suppression of numerous emetogenic peripheral stimuli and central neuroemetic receptors may be necessary. This multimodal PONV management approach includes use of: (i) multiple different antiemetic medications (double or triple combination antiemetic therapy acting at different neuroreceptor sites); (ii) less emetogenic anaesthesia techniques; (iii) adequate intravenous hydration; and (iv) adequate pain control.
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PMID:Prevention and treatment of postoperative nausea and vomiting. 1073 May 46

Insomnia is the most frequently encountered sleep complaint worldwide. While many prescription drugs are used to treat insomnia, extracts of valerian (Valeriana officinalis L., Valerianaceae) are also used for the treatment of insomnia and restlessness. To determine novel mechanisms of action, radioligand binding studies were performed with valerian extracts (100% methanol, 50% methanol, dichloromethane [DCM], and petroleum ether [PE]) at the melatonin, glutamate, and GABA(A) receptors, and 8 serotonin receptor subtypes. Both DCM and PE extracts had strong binding affinity to the 5-HT(5a) receptor, but only weak binding affinity to the 5-HT(2b) and the serotonin transporter. Subsequent binding studies focused on the 5-HT(5a) receptor due to the distribution of this receptor in the suprachiasmatic nucleus of the brain, which is implicated in the sleep-wake cycle. The PE extract inhibited [(3)H]lysergic acid diethylamide (LSD) binding to the human 5-HT(5a) receptor (86% at 50 microg/ml) and the DCM extract inhibited LSD binding by 51%. Generation of an IC(50) curve for the PE extract produced a biphasic curve, thus GTP shift experiments were also performed. In the absence of GTP, the competition curve was biphasic (two affinity sites) with an IC(50) of 15.7 ng/ml for the high-affinity state and 27.7 microg/ml for the low-affinity state. The addition of GTP (100 microM) resulted in a right-hand shift of the binding curve with an IC(50) of 11.4 microg/ml. Valerenic acid, the active constituent of both extracts, had an IC(50) of 17.2 microM. These results indicate that valerian and valerenic acid are new partial agonists of the 5-HT(5a) receptor.
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PMID:Valerian extract and valerenic acid are partial agonists of the 5-HT5a receptor in vitro. 1592 20

Aripiprazole is a new chemical entity with a unique pharmacological profile. It has strong affinities for certain dopamine receptors, and intermediate affinity for serotonin, adrenergic and histamine receptors. Partial agonism of the D2 dopamine and 5HT1A serotonin receptors, and antagonism of the 5HT2 serotonin receptor are believed to be the functional basis of its therapeutic efficacy. Its clinical effects are best documented in patients suffering from schizophrenia and bipolar disorder, in which it has been demonstrated to have antipsychotic and antimanic properties superior to placebo in dose ranges of 10-30 mg/day. Two published longer term trials document maintenance of antipsychotic effects and relapse prevention in schizophrenia patients. In general, aripiprazole seems to be a well-tolerated drug, especially with regard to metabolic side effects. The most commonly reported side effects include restlessness/akathisia, somnolence and nausea. These may be dose-dependent and usually occur early on during treatment, with many patients developing tolerance. Aripiprazole is an interesting and important addition to the currently available spectrum of antipsychotic drugs. Further studies in other indications and clinical trials that confirm results from the Phase II and III clinical development programme are eagerly awaited.
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PMID:Aripiprazole. 1619 61

The Neuropsychiatric Inventory (NPI) was introduced in 1994 and has since become a standard instrument for clinical trials and other types of behavioral research in dementing disorders. Its reliability and validity have been confirmed. The NPI was the subject of a workshop in Asia in conjunction with the International Workgroup on Dementia Drug Guidelines (IWG). Investigators using the NPI from 4 Asian areas--Taiwan, Hong Kong, Japan, Thailand--presented conclusions from their research. A high prevalence of behavioral disturbances across Asian countries was found and the rates are similar to those observed in Western countries. Apathy is more difficult to detect and characterize in Asian populations. Neurobiologic studies show an excess of some serotonin receptor gene polymorphisms in patients without behavioral disturbances and positron emission tomography reveals reductions in frontal lobe metabolism in patients manifesting depression as measured by the NPI. Studies in Thailand show relationships among verbal fluency, activities of daily living, and neuropsychiatric symptoms particularly agitation, apathy, and disinhibition. This suggests a triad of symptoms of behavioral abnormalities, executive dysfunction, and abnormalities of activities of daily living that impugn frontal lobe function. The NPI is a reliable and useful instrument to characterize behavioral changes in Asian and Western populations.
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PMID:Neuropsychiatric inventory workshop: behavioral and psychologic symptoms of dementia in Asia. 1713 81

Suboxone (buprenorphine/naloxone) is an oral medication used for the treatment of opiate dependence. Because of its mixed properties at the opiate receptors, buprenorphine has a ceiling on its euphoric effects. We report the first case of serotonin syndrome caused by buprenorphine and review other medications implicated in serotonin syndrome. A 54-year-old man on tricyclic antidepressants took an unprescribed dose of buprenorphine/naloxone. He presented to the emergency department with signs and symptoms of severe serotonin syndrome including clonus, agitation, and altered mental status. His agitation was not controlled with benzodiazepines and was electively intubated. At the recommendation of the toxicology service, cyproheptadine, a serotonin receptor antagonist, was administered with improvement in the patient's symptoms. Emergency physicians should be aware of the potential of buprenorphine/naloxone to trigger serotonin syndrome.
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PMID:Serotonin syndrome triggered by a single dose of suboxone. 1877 63

The serotonin syndrome is a toxic state largely attributable to changes in sensitivity of serotonin receptor system in the brainstem and spinal cord resulting from increased serotonergic activity in central neurologic system, due to use of serotonergic agents either in overdose or in combination. Serotonin syndrome may present with neuromuscular (clonus, myoclonus, tremor, hyperreflexia) and autonomic (fever, mydriasis, tachycardia, tachypnea) symptoms and mental status changes (confusion, agitation) and may result in death in severe cases. The risk for the development of serotonin syndrome is increased with the combined use of agents from different groups such as selective serotonin reuptake inhibitors (SSRIs) and monoamine oxidase inhibitors (MAOIs). The growing use of SSRIs for depression and the introduction of pharmacological agents newly developed for the treatment of various medical disorders increases the risk of drug-drug interactions and toxic states like serotonin syndrome. In the presented case clinical presentation and outcome of the serotonin syndrome which has developed as a consequence of concomitant linezolid use in a young patient who was already on an SSRI antidepressant is discussed. Linezolid is an oxazolidinone antibiotic which has MAOI-like properties. This case is presented to inform psychiatrists especially working in consultation-liaison settings about the risk of drug-drug interactions and possible prevention of these.
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PMID:[Serotonin syndrome associated with linezolid use: a case report]. 2001 32

The serotonin receptor gene (5-HT2A) has been reported to be a susceptible factor in behavioral and psychological symptoms of dementia (BPSD) in Alzheimer's disease (AD). However, previous results were conflicting. We aim to investigate the association of 5-HT2A T102C with BPSD in AD using a meta-analysis. Studies were collected using PubMed, Web of Science, the Cochrane Library databases, Chinese National Knowledge Infrastructure (CNKI), and Embase. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess associations. Nine studies with 1899 AD patients with/without BPSD were included in this meta-analysis. The 102C and CC genotypes were associated with psychosis in AD (102C: p < 0.00001, OR [95% CI] = 3.19 [2.12-4.79]; CC: p < 0.00001, OR [95% CI] = 7.24 [3.60-14.59]). The TT genotype was significantly associated with hallucinations, aberrant motor behavior, and psychosis in AD (hallucinations: p = 0.001, OR [95% CI] = 0.52 [0.36-0.77]; aberrant motor behavior: p = 0.03, OR [95% CI] = 0.58 [0.35-0.95]; and psychosis: p = 0.002, OR [95% CI] = 0.34 [0.17-0.67]). No association was observed between T102C alleles or genotypes and delusions, agitation/aggression, depression, and apathy (p > 0.05). Thus, the 5HT2A T102C might be a susceptible factor for hallucinations, aberrant motor behavior, and psychosis in AD. The potential mechanism of this polymorphism in BPSD in AD requires further exploration.
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PMID:The Association between 5HT2A T102C and Behavioral and Psychological Symptoms of Dementia in Alzheimer's Disease: A Meta-Analysis. 2934 76