Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0220723 (PCA)
 4,687 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pro- and anticonvulsant effects of phencyclidine (1-[1-phenylcyclohexyl]piperidine HCl, PCP), a number of its analogues, and SKF 10047 were investigated in rats. The PCP analogues were compounds produced by substitutions for the phenyl and piperidine rings of PCP and were selected to elucidate the structure-activity relationships existing between PCP and its pro- and/or anticonvulsant effects. All of the compounds, except ketamine, induced convulsions at high (12.8-25.6 mg/kg, i.v.), yet almost always sublethal doses. Ketamine failed to induce convulsions, even at lethal doses (51.2 mg/kg, i.v.). The acute pro- or anticonvulsant actions of PCP were then investigated. Rats were subjected to transorbital electroconvulsive shock subsequent to i.p. injections of saline or 0.625, 2.5, 5.0, 10.0 or 20.0 mg/kg PCP. It was found that PCP induced an acute, dose-dependent anticonvulsant effect. The acute pro- and/or anticonvulsant actions of the remaining compounds were then investigated by administration of electroconvulsive shock subsequent to i.p. injections of saline or one of two doses of each compound. The low and high doses of each compound were selected to be behaviorally equivalent to 2.5 and 10.0 mg/kg PCP i.p., respectively. With one exception, each dose of each drug induced an acute anticonvulsant action, with no difference in efficacy between the compounds tested. However, PCA (produced by substitution of an amine for the piperidine ring of PCP) induced a statistically greater anticonvulsant action at the higher, compared to the lower, dose. In addition, PCA was the only compound to eliminate all motor signs of the electrically induced seizure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The convulsant and anticonvulsant effects of phencyclidine (PCP) and PCP analogues in the rat. 396 7

Several situations arise in the PICU patient that require the administration of drugs for sedation and analgesia. A "cookbook" approach is impossible because of the diversity of patient and clinical scenarios. When amnesia is required, these authors prefer a continuous infusion of a benzodiazepine such as midazolam or lorazepam. Although the majority of clinical experience has been with midazolam, lorazepam either by bolus dose or continuous infusion offers a cost-effective alternative. When analgesia is required, the addition of a continuous infusion of narcotic or the use of a PCA device in the older patient should prove effective. Although fentanyl is frequently chosen, morphine is an effective and cost-effective alternative for patients with stable cardiovascular function. The synthetic narcotics are recommended for neonates, especially following cardiac surgical procedures and those at risk for pulmonary vasospasm. Narcotics may also be used for the treatment of agitation in those situations that do not necessarily require analgesia. Our clinical experience suggests that narcotics may be more effective for sedation than benzodiazepines in children less than 1 year of age. When the above agents fail to be effective or are associated with cardiovascular depression, alternatives may include ketamine or pentobarbital. Ketamine may be useful for the unstable patient or those with a bronchospastic component to their disease process. We have found pentobarbital to be effective when the combination of benzodiazepines and narcotics fails to provide the desired level of sedation. Aside from these techniques, regional anesthesia may offer a more effective means of controlling pain in the PICU patient. These techniques may be effective when parenteral narcotics are inadequate or lead to undesired effects. Although most commonly used for postoperative analgesia, their use in patients with pain from other causes (e.g., multiple trauma) may be indicated, especially when parenteral narcotics may interfere with respiratory function or the ongoing assessment of the patient's mental status.
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PMID:Pain management and sedation in the pediatric intensive care unit. 798 86

Ketamine, an N-methyl-D-aspartate receptor antagonist, is known to be analgesic and to induce psychomimetic effects. Benefits and risks of ketamine for the control of postoperative pain are not well understood. We systematically searched for randomised comparisons of ketamine with inactive controls in surgical patients, reporting on pain outcomes, opioid sparing, and adverse effects. Data were combined using a fixed effect model. Fifty-three trials (2839 patients) from 25 countries reported on a large variety of different ketamine regimens and surgical settings. Sixteen studies tested prophylactic intravenous ketamine (median dose 0.4 mg/kg, range (0.1-1.6)) in 850 adults. Weighted mean difference (WMD) for postoperative pain intensity (0-10 cm visual analogue scale) was -0.89 cm at 6 h, -0.42 at 12 h, -0.35 at 24 h and -0.27 at 48 h. Cumulative morphine consumption at 24 h was significantly decreased with ketamine (WMD -15.7 mg). There was no difference in morphine-related adverse effects. The other 37 trials tested in adults or children, prophylactic or therapeutic ketamine orally, intramuscularly, subcutaneously, intra-articulary, caudally, epidurally, transdermally, peripherally or added to a PCA device; meta-analyses were deemed inappropriate. The highest risk of hallucinations was in awake or sedated patients receiving ketamine without benzodiazepine; compared with controls, the odds ratio (OR) was 2.32 (95%CI, 1.09-4.92), number-needed-to-harm (NNH) 21. In patients undergoing general anaesthesia, the incidence of hallucinations was low and independent of benzodiazepine premedication; OR 1.49 (95%CI 0.18-12.6), NNH 286. Despite many published randomised trials, the role of ketamine, as a component of perioperative analgesia, remains unclear.
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PMID:Ketamine and postoperative pain--a quantitative systematic review of randomised trials. 1562 65

Ketamine inappropriate use has been associated with serious consequences for human health. Anesthetic properties of ketamine are well-known, but its side effects are poorly described, including the effects on anxiety. In this context, animal models are a safe way to conduct this neurobehavioral research and zebrafish (Danio rerio) is an interesting model which has several advantages. The validation and interpretation of results of behavioral assays requires a suitable statistical approach, and the use of multivariate statistical methods has been little explored, especially in zebrafish behavioral models. Here, we investigated the anxiolytic-induced effects of ketamine in adult zebrafish, using Light-Dark Test and proposing the Multivariate Statistics methods (PCA, HCA and SIMCA) to analyze the results. In addition, we compared the processing of data to the one carried out by analysis of variance (ANOVA) ketamine produced significant concentration of exposure-dependent anxiolytic effects, increasing time in white area and number of crossings and decreasing latency to first access to white area. Average entry duration behavior resulted in a slight decrease from control to treatment groups, with an observed concentration-dependent increase among the exposed groups. PCA results indicated that two principal components represent 88.74% of all the system information. HCA and PCA results showed a higher similarity among control and treatment groups exposed to lower concentrations of ketamine and among treatment groups exposed to concentrations of 40 and 60 mg L(-1). In SIMCA results, interclasses distances were concentration of exposure-dependent increased and misclassifications and interclasses residues results also support these findings. These findings confirm the anxiolytic potential of ketamine and zebrafish sensibility to this drug. In summary, our study confirms that zebrafish and multivariate statistics data validation are an appropriate and viable behavioral model for the study of psychoactive substances, providing a detailed and reliable analysis.
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PMID:Ketamine induces anxiolytic effects in adult zebrafish: A multivariate statistics approach. 2618 88