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)

The effects of selected centrally acting drugs on sleep after single administration to rats and humans were studied using polygraphic sleep recording techniques. D-Amphetamine, a stimulant, had similar effects in both species: reduction of total sleep time, of N(non-)REM- and particularly REM (rapid eye movement)-sleep, increased restlessness during sleep. The psychodepressants mesoridazine and, in particular, nitrazepam had relatively little effects on sleep stages. In doses which did not cause side effects they reduced restlessness during sleep. The most typical effect of the antidepressant imipramine was a dose dependent reduction of REM-sleep duration in both species, without impairment of NREM-sleep. The central dopamine agonist, bromocriptin, had little effect on sleep and did not reduce total sleep and REM-sleep. These examples suggest that polygraphic sleep studies are a sensitive and stable method for the study of centrally acting drugs. The specificity of the model is illustrated by its ability to differentiate chemically and pharmacologically different drug classes. The validity of the model, i.e., its ability to allow predictions from the laboratory conditions to the therapeutic situation, varies in different drug classes. Investigations in normal subjects and animals appear to be relevant for the study of CNS-stimulants, whereas for CNS-depressants studies in sleep-disturbed subjects or animals are more likely to provide dependable results.
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PMID:Polygraphic sleep studies in rats and humans: their use in psychopharmacological research. 98 73

Amphetamine intoxication in dogs referred to the Veterinary Diagnostic Laboratory or the Veterinary Hospital of the University of Minnesota was characterized by excitement, agitation, hyperthermia, and convulsive episodes that could be confused with other convulsant poisonings. Extraction procedures on stomach contents or urine enabled indentification of the drug, using ultraviolet spectrophotometry.
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PMID:Amphetamine poisoning in dogs. 125 19

Preclinical studies suggest that 5-HT3 antagonists modulate dopamine-mediated responses in the limbic system and may therefore have a therapeutic role in psychiatry. We have examined the effect of ondansetron, a specific 5-HT3 antagonist, on the psychological and psychomotor changes induced by amphetamine in human volunteers. Nine healthy males took part in this double-blind placebo-controlled balanced-crossover study. Each subject received one of three treatments in a randomised manner: (a) placebo/placebo; (b) placebo/amphetamine (15 mg); (c) ondansetron (4 mg)/amphetamine (15 mg). Subjects were assessed for self-ratings of hunger, mood, energy, alertness, restlessness, irritability, and asked to rate the abnormality of their overall subjective state. In addition, systolic blood pressure, and performance on psychomotor tests were repeatedly assessed. Although amphetamine did not cause any significant changes in self-rating of mood, energy, alterness, restlessness or irritability, it induced a significant increase in self-ratings for overall subjective state, and a significant decrease in self-ratings of hunger. Amphetamine also caused an increase in systolic blood pressure and a decrease in the mean time taken to complete the psychomotor tests. Pretreatment with ondansetron attenuated the effects of amphetamine on hunger and subjective state, but not on blood pressure or psychomotor performance tests. These findings suggest that in humans 5-HT3 receptor antagonists may partially modify the subjective effects of amphetamine, and are in keeping with results from animal studies that 5-HT3 receptor antagonists might affect neurotransmission within mesolimbic brain regions. However, it was not possible to exclude a pharmacokinetic interaction to explain the effects of ondansetron.
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PMID:Ondansetron, a 5-HT3 receptor antagonist, partially attenuates the effects of amphetamine: a pilot study in healthy volunteers. 138 3

Amphetamine poisoning is rare in children. Here we report two male infants with acute poisoning due to accidental amphetamine ingestion. One infant had a family history of drug abuse and the other was due to poor supervision of the parents. Although typical clinical symptoms and signs (including restlessness, hyperactivity, hypertension, tachycardia and tachypnea....etc.) were found, both were completely recovered after treatment. The principle of management of amphetamine poisoning are presented.
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PMID:Amphetamine poisoning in infant: report of two cases. 165 42

State-dependent learning and memory (retrieval) processes were examined in 15 amphetamine-treated hyperactive boys. While stimulant treatment enhanced the acquisition of information and its retrieval 24 hours later, there was no evidence of poorer retrieval of information learned in a state different from the retrieval state. Amphetamine appeared particularly to facilitate effortful cognitive processes. Subgroups of hyperactive children respond to amphetamine treatment in different ways, some showing changes in motor restlessness and others changes in cognition. The lack of dissociative effects when information is learned and recalled under different drug conditions suggests that what the stimulant-treated child learns can be effectively recovered after completion of treatment.
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PMID:Acquisition and retrieval of information in amphetamine-treated hyperactive children. 694 68

1. Akathisia describes the pattern of intense inner restlessness often associated with neuroleptic and antidepressant treatment. 2. The authors postulated that drug-induced akathisia would be characterized by more position changes and less time spent immobile, in the absence of significant increase in ambulation. In contrast, a psychomotor stimulant would produce both activation and ambulation. 3. Procedures and instruments were developed to test this hypothesis. Adult rats were habituated for 72 hours to the testing environment, and their precise pattern of movements was tracked and recorded (10 reading per second; resolution 0.04 mm) by an infrared motion analysis system. Activity was recorded for a 90 min period after a single injection of sub-stereotypic doses of d-amphetamine (0, 0.3, 1.0 mg/kg) or racemic fluoxetine (0, 3.0, 10.0, 20.0, or 30.0 mg/kg, s.c.). 4. Amphetamine produced both activation and ambulation. Activation was indicated by a decrease in time spent immobile, and an increase in the temporal scaling exponent, which reflects the degree the animal is "acting' in its environment, and the number of position changes. Enhanced locomotion was inferred from marked increases in both the total distance traversed and the ratio of forward movements-to-reversals and a decrease in the spatial scaling exponent, indicative of a less complex and more linear movement pattern. 5. Fluoxetine caused animals to spend more time active, but exerted little effect on locomotion. Activation was indicated by a decrease in time spent immobile and an increase in the temporal scaling exponent and number of position changes. Fluoxetine failed to significantly effect either the ratio of forward movements-to-reversals or the spatial scaling exponent. 6. These findings provide an operational definition and methodology that can be used to differentiate between psychostimulant effects and akathisic effects. This approach may have utility for screening drugs for akathisic potential, for exploring underlying mechanisms, and for developing novel treatments.
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PMID:Development of an animal model of fluoxetine akathisia. 886 11

This case report describes an acute overdose in a female patient with the serotonin mixed agonist-antagonist m-chlorophenylpiperazine (mCPP), a new synthetic drug that is also a metabolite of the antidepressant trazodone. Following ingestion of three multi-coloured tablets, she developed anxiety, agitation, drowsiness, flushing, visual disturbances and tachycardia. The mCPP concentration was 320 ng/mL in plasma and 2300 ng/mL in urine. Amphetamine (40 ng/mL), benzoylecgonine (47 ng/mL) and alcohol (0.7 g/L) were also detected in plasma. The concentration of mCPP in plasma was approximately six times higher than the usual concentration measured in patients under trazodone treatment (26-108 ng/mL, average 56 ng/mL). However, one should be careful to link the observed symptoms to the use of mCPP only as the other drugs that have also been taken or an interaction between the drugs could also have played a role.
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PMID:Acute chlorophenylpiperazine overdose: a case report and review of the literature. 1852 Jun 13

The prevalence of attention-deficit hyperactivity disorder (ADHD) in the USA is estimated at approximately 4-9% in children and 4% in adults. It is estimated that prescriptions for ADHD medications are written for more than 2.7 million children per year. In 2010, US poison centers reported 17,000 human exposures to ADHD medications, with 80% occurring in children <19 years old and 20% in adults. The drugs used for the treatment of ADHD are diverse but can be roughly separated into two groups: the stimulants such as amphetamine, methylphenidate, and modafinil; and the non-stimulants such as atomoxetine, guanfacine, and clonidine. This review focuses on mechanisms of toxicity after overdose with ADHD medications, clinical effects from overdose, and management. Amphetamine, dextroamphetamine, and methylphenidate act as substrates for the cellular monoamine transporter, especially the dopamine transporter (DAT) and less so the norepinephrine (NET) and serotonin transporter. The mechanism of toxicity is primarily related to excessive extracellular dopamine, norepinephrine, and serotonin. The primary clinical syndrome involves prominent neurological and cardiovascular effects, but secondary complications can involve renal, muscle, pulmonary, and gastrointestinal (GI) effects. In overdose, the patient may present with mydriasis, tremor, agitation, hyperreflexia, combative behavior, confusion, hallucinations, delirium, anxiety, paranoia, movement disorders, and seizures. The management of amphetamine, dextroamphetamine, and methylphenidate overdose is largely supportive, with a focus on interruption of the sympathomimetic syndrome with judicious use of benzodiazepines. In cases where agitation, delirium, and movement disorders are unresponsive to benzodiazepines, second-line therapies include antipsychotics such as ziprasidone or haloperidol, central alpha-adrenoreceptor agonists such as dexmedetomidine, or propofol. Modafinil is not US FDA approved for treatment of ADHD; however, it has been shown to improve ADHD signs and symptoms and has been used as an off-label pharmaceutical for this diagnosis in both adults and children. The mechanism of action of modafinil is complex and not fully understood. It is known to cause an increase in extracellular concentrations of dopamine, norepinephrine, and serotonin in the neocortex. Overdose with modafinil is generally of moderate severity, with reported ingestions of doses up to 8 g. The most common neurological effects include increased anxiety, agitation, headache, dizziness, insomnia, tremors, and dystonia. The management of modafinil overdose is largely supportive, with a focus on sedation, and control of dyskinesias and blood pressure. Atomoxetine is a selective presynaptic norepinephrine transporter inhibitor. The clinical presentation after overdose with atomoxetine has generally been mild. The primary effects have been drowsiness, agitation, hyperactivity, GI upset, tremor, hyperreflexia, tachycardia hypertension, and seizure. The management of atomoxetine overdose is largely supportive, with a focus on sedation, and control of dyskinesias and seizures. Clonidine is a synthetic imidazole derivative with both central and peripheral alpha-adrenergic agonist actions. The primary clinical syndrome involves prominent neurological and cardiovascular effects, with the most commonly reported features of depressed sensorium, bradycardia, and hypotension. While clonidine is an anti-hypertensive medication, a paradoxical hypertension may occur early with overdose. The clinical syndrome after overdose of guanfacine may be mixed depending on central or peripheral alpha-adrenoreceptor effects. Initial clinical effects may be drowsiness, lethargy, dry mouth, and diaphoresis. Cardiovascular effects may depend on time post-ingestion and may present as hypotension or hypertension. The management of guanfacine overdose is largely supportive, with a focus on support of blood pressure. Overdose with ADHD medications can produce major morbidity, with many cases requiring intensive care medicine and prolonged hospital stays. However, fatalities are rare with appropriate care.
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PMID:Overdose of drugs for attention-deficit hyperactivity disorder: clinical presentation, mechanisms of toxicity, and management. 2375 86

Amphetamine induced ischaemic colitis is an exceedingly rare presentation of amphetamine toxicity. The cases reported in the literature have described mild or transient disease. We present a fatal case of ischaemic colitis induced by amphetamine use in a 44-year-old woman who presented in extremis after a cardiac arrest en route to the emergency department. A short history of headache, abdominal pain, vomiting and agitation preceded her admission. Imaging revealed changes consistent with ischaemic colitis. Emergency laparotomy revealed widespread colonic necrosis necessitating a subtotal colectomy. Despite aggressive resuscitation and inotropic support from arrival, the patient deteriorated intraoperatively and died in the immediate postoperative period. Histology showed arterial type ischaemia/reperfusion injury of the area supplied by the superior mesenteric artery. The patient's serum amphetamine level was 0.52mg/l (peak therapeutic levels <0.2mg/l). The postmortem examination concluded that amphetamines were the likely cause of the vasospasm, leading to profound colonic ischaemia.
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PMID:A fatal case of amphetamine induced ischaemic colitis. 2885 4

Captagon, known by its genetic name Fenethylline, is an addictive drug that complicates the War on Drugs. Captagon has a strong CNS stimulating effect than its primary metabolite, Amphetamine. However, multi-targets issues associated with the drug and metabolites as well as its underlying mechanisms have not been fully defined. In the present work, we applied our established drug-abuse chemogenomics-knowledgebase systems pharmacology approach to conduct targets/off-targets mapping (SP-Targets) investigation of Captagon and its metabolites for hallucination addiction, and also analyzed the cell signaling pathways for both Amphetamine and Theophylline with data mining of available literature. Of note, Amphetamine, an agonist for trace amine-associated receptor 1 (TAAR1) with enhancing dopamine signaling (increase of irritability, aggression, etc.), is the main cause of Captagon addiction; Theophylline, an antagonist that blocks adenosine receptors (e.g. A2aR) in the brain responsible for restlessness and painlessness, may attenuate the behavioral sensitization caused by Amphetamine. We uncovered that Theophylline's metabolism and elimination could be retarded due to competition and/or blockage of the CYP2D6 enzyme by Amphetamine; We also found that the synergies between these two metabolites cause Captagon's psychoactive effects to act faster and far more potently than those of Amphetamine alone. We carried out further molecular docking modeling and molecular dynamics simulation to explore the molecular interactions between Amphetamine and Theophylline and their important GPCRs targets, including TAAR1 and adenosine receptors. All of the systems pharmacology analyses and results will shed light insight into a better understanding of Captagon addiction and future drug abuse prevention.
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PMID:Insight of Captagon Abuse by Chemogenomics Knowledgebase-guided Systems Pharmacology Target Mapping Analyses. 3078 22


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