Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.16.2 (PCP)
 3,761 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The history, symptoms, diagnosis and treatment of phencyclidine hydrochloride (PCP) intoxication and the pharmacology of PCP are reviewed. Intoxication with low to moderate doses of PCP (5-20 mg) resembles an acute, confusional state generally lasting four to six hours. High doses (greater than 20 mg) may cause serious neurologic and cardiovascular complications and the patient is often comatose for several days. Treatment involves supportive psychological and medical measures. Evacuation of the stomach with activated charcoal and a saline cathartic may be indicated and succinylcholine chloride may ease intubation. Diazepam and chlorpromazine may be used to control the combative patient and the "PCP psychosis" patient, respectively. Antihypertensive agents are not usually needed, but diazoxide and hydralazine hydrochloride have been used to treat hypertensive crises. Diazepam and phenytoin have been used to treat seizures. Ion-trapping by continuous gastric suctioning and by urine acidification with ammonium chloride may increase clearance of PCP. Forced diuresis with furosemide in conjunction with acidification may further increase PCP clearance. Use of physostigmine is based on conjecture.
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PMID:Phencyclidine intoxication: a literature review. 36 Aug 32

Studies were conducted to determine whether single or combination treatments of charcoal, paraffin, cholestyramine, and/or ammonium chloride (NH4Cl), would alter the rotarod-measured motor dysfunction induced by 10 to 90 mg/kg of phencyclidine (PCP). Additionally, the effect of NH4Cl/charcoal treatment of the biodisposition of 50 mg/kg PCP was evaluated in order to assess whether amelioration of behavioral effects could be correlated to alterations in brain levels, plasma levels, and/or the renal clearance of PCP and metabolites. NH4Cl/charcoal treatment proved more effective at reducing intoxication than either treatment singly, though effectiveness was reduced by larger doses of PCP. NH4Cl/charcoal treatment reduced intoxification by 40, 16, and 21% at PCP doses of 10, 25, and 50 mg/kg. However, the reduction in motor dysfunction observed at 25 and 50 mg/kg PCP was greater than the sum of the individual treatments. In contrast, the effect of combined NH4Cl and charcoal treatment on the biodisposition of 50 mg/kg PCP is not synergistic, but appears instead to be due simply to the additive effects of the individual treatments. Thus the amelioration of PCP intoxication cannot be fully explained by alterations in PCP biodisposition.
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PMID:Modification of phencyclidine intoxification and biodisposition by charcoal and other treatments. 317 69

Purified Torpedo nobiliana electric organ acetylcholine receptor (AChR) was reconstituted into membranes containing natural phospholipids supplemented with cholesterol (25% w/w). The reconstituted system facilitates the study of the effects of drugs on the regulation of the AChR channel complex under both resting and carbachol (carb)-stimulated conditions. Neostigmine (Neo) was the only carbamate to induce activation of [3-H]-phencyclidine ([3-H]-PCP) binding to the channel sites, acting as a weak agonist. The activation of [3-H]-PCP binding is dependent upon the nature of the reconstituted systems, with carb/Neo activation ratios of 8, 3, and 1 for the intact purified AChR vesicles fraction (PVF), the PVF reconstituted in phospholipid/cholesterol (CRPVF), and the PVF reconstituted in phospholipid (RPVF), respectively. The carbamates Neo, physostigmine (Physo), and pyridostigmine (Pyrido) inhibited carb-activated [3-H]-PCP binding with Ki values of 10, 20, and 1,600 microM, respectively. The inhibition was mixed competitive-noncompetitive in nature. The characteristic response of CRPVF to carb-stimulated [22-Na] influx was inhibited by the three carbamates, with IC-50 values of 6, 50, and 1,000 microM for Neo, Physo, and Pyrido, respectively. The quaternary ammonium organophosphate ecothiophate (Eco) inhibited carb-stimulated [22-Na] influx with potency similar to that of Neo. Preincubation of AChR preparation with the carbamates and ecothiophate caused a reduction in the binding of [125-I]-alpha-bungarotoxin ([125-I]-alpha-BGT) with the following decreasing order of potency: Neo less than Physo less than Eco less than Pyrido. Calcium has a direct modulatory role on the time-course inhibition of [125-I]-alpha-BGT binding by these drugs. While we observed a high potency of Neo and Physo in inhibiting [125-I]-alpha-BGT binding, it was undetectable for the carbamate insecticide 2-methyl-2-(methylthio)propionaldehyde-O-(methylcarbamoyl)oxime (aldicarb). These data suggest that the potent anticholinesterase carbamate agents interact differently with the AChR and its ionic channel. Their interactions with the nicotinic AChR channel system can be described as (a) weakly agonist, (b) directly acting on the open conformation of the channel, and (c) blocking the AChR-binding sites.
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PMID:Biochemical interactions of carbamates and ecothiophate with the activated conformation of nicotinic acetylcholine receptor. 350 76

Urinary acidification is widely used to increase the excretion rate of PCP in abusers. Various acidifying techniques were used and compared with regard to efficacy in lowering pH, side effects, and patient acceptability. On the basis of our findings and data from routine monitoring with test tapes, we would recommend the following acidifications procedures as efficacious and reasonably well tolerated: Ammonium chloride, 4 gm. per day, 1 gm. q.i.d., with sufficient water or cranberry juice. Lysine dihydrochloride, 6 gm. per day, 2 gm. t.i.d., with sufficient water or cranberry juice. Lysine hydrochloride, 8 gm. per day, 2 gm. q.i.d., with water or cranberry juice. Cranberry juice, 18 or more oz. per day alone, or plus lysine, ammonium chloride, or ascorbic acid.
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PMID:Urinary acidifiers in phencyclidine detoxification. 642 7

A proline dipeptidase (EC 3.4.13.9) from guinea pig brain was purified to over 90% homogeneity by a combination of ammonium sulfate fractionation, DEAE-cellulose chromatography, calcium phosphate-cellulose chromatography, chromatofocusing, and gel filtration on Sephadex G-200. A purification factor of 2718-fold was obtained with a yield of 7%. The purified enzyme was found to have an apparent molecular weight of 132,000 and to consist of two dissimilar subunits of molecular weights 64,000 and 68,000. The substrate specificity of the enzyme is not that of a strict proline dipeptidase. Although it preferentially hydrolyzes proline dipeptides (Leu-Pro) it also hydrolyzes prolyl dipeptides (Pro-Leu) and dipeptides not containing proline (Leu-Leu). The purified enzyme preparation exhibited weak aminoacylproline aminopeptidase activity against Arg-Pro-Pro but it did not exhibit any post-proline dipeptidyl aminopeptidase, post-proline cleaving endopeptidase, proline iminopeptidase, prolyl carboxypeptidase or carboxypeptidase P activities when tested with a large variety of peptides and arylamides. With all of the proline and prolyl dipeptides examined the enzyme exhibited biphasic kinetics (two distinct slopes on Lineweaver-Burk plots). However, with Leu-Leu as substrate normal Michaelis-Menten kinetics were obeyed.
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PMID:The purification and characterization of a proline dipeptidase from guinea pig brain. 685 81

Subeffective doses (0.5 mg) of 3H-phencyclidine (PCP) were given intravenously to three healthy men under two regimens designed to alkalinize or acidify their urine (oral sodium bicarbonate or ammonium chloride). The concentrations of PCP and its metabolites in saliva, plasma, and urine for 7 hr after injection were determined by high-performance liquid radiochromatography. A sample of perspiration from one subject was analyzed. The effects of physical exercise on the plasma concentration and urinary excretion of PCP were also studied. Multiple linear regression analysis showed the logarithm of renal clearance the renal clearance of PCP. PCP and its metabolites are also excreted in perspiration. Our results support clinical reports of the importance of vigorous acidification of urine and diuresis in treatment of PCP intoxication.
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PMID:Urine pH and phencyclidine excretion. 712 4

An immunogen was prepared from a succinamide derivative preparation of phencyclidine (PCP) and coupled to bovine gamma globulin by means of water-soluble carbodiimide. Phencyclidine, 10 of its analogs, and a 3,4-3H-PCP all bound competitively to antibodies induced in rabbits. An assay was developed using the ammonium sulfate precipitation separation method. The minimum detection limit to PCP was 2 ng/mL and that for various analogs ranged from 50 pg/mL to approximately 100 ng/mL. No cross reactivity was observed with at least 25 commonly used drugs. A double blind qualitative clinical evaluation of the assay was conducted with gas-liquid chromatography (GLC) and GLC-mass spectrometry methods. No false positive or false negative results were observed. For qualitative screening a "cut-off" level equivalent to 5 ng/mL was used for both serum and urine to distinguish between positive and negative specimens. Urine and serum samples from emergency room patients with neuropsychiatric symptoms and methadone clinic patients and autopsy material showed a significant incidence of PCP abuse, particularly among adolescents and young adults.
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PMID:Radioimmunoassay screening test for detection of phencyclidine (PCP, "angel dust") abuse among teenagers. 719 88

In a laboratory experiment, effects of chemical stress (pentachlorophenol, PCP, at concentrations of 0, 50, and 500 mg/kg) and biotic interactions (nematodes in the presence or absence of collembolas and enchytraeids) on the community structure of soil animals and decomposition processes were studied. PCP was strongly adsorbed to humus that contained 65% organic matter. Numbers of fungal-feeding nematodes decreased significantly at the highest PCP concentration, while no effects were found in bacterial feeders. There were differences in the numbers of nematodes between different animal combinations, but at the highest PCP concentration, collembolas and enchytraeids had no effect on them. Numbers of collembola Willemia anophtalma were lowered at the highest PCP concentration, although PCP was not acutely toxic at this concentration. The highest PCP concentration was acutely toxic to enchytraeids, and for an unknown reason all of them died in the main experiment. Both ATP content of the soil and soil respiration were reduced at the highest PCP concentration, while no differences were found between animal treatments. Amounts of NH4-N and PO4-P in the soil increased with increasing PCP concentration. It was concluded that in the presence of simple animal communities, harmful chemicals like PCP regulate the community structure of soil animals as well as decomposition and nutrient mobilization.
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PMID:Effects of pentachlorophenol and biotic interactions on soil fauna and decomposition in humus soil. 749 64

Prolylcarboxypeptidase (Angiotensinase C, EC 3.4.16.2) was purified to homogeneity from cell free extracts of Xanthomonas maltophilia by ammonium sulfate fractionation and sequential chromatographies on DEAE-Toyopearl, Sephadex G-150, FPLC-Hiload Superdex 200 pg, and FPLC-Hitrap SP columns, with an activity recovery of 15%. The molecular weight of the enzyme was found to be 330,000 by gel filtration and 83,000 by SDS-PAGE, suggesting a tetrameric form for the native enzyme. It had an optimum pH of 8.5 and stability between pH 8.0 and 11.0. The isoelectric point of the enzyme was 6.6. The enzyme hydrolyzed Pro-X bonds when proline was in the penultimate position from the carboxyl terminal. The enzyme was strongly inhibited by diisopropylfluorophosphate (DFP), while phenylmethylsulfonyl fluoride (PMSF), p-chloromercuribenzoic acid (PCMB), iodoacetamide, and metal chelators had no effect.
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PMID:Prolylcarboxypeptidase (angiotensinase C): purification and characterization of the enzyme from Xanthomanas maltophilia. 776 28

A simple and rapid screening procedure with Triage has been developed to detect 7 classes of drugs of abuse, phencyclidine (PCP), benzodiazepines (BZO), cocaine metabolite (COC), amphetamines (AMP), cannabinoids (THC), opiates (OPI), and barbiturates (BAR), in hemolyzed blood. A clear supernatant was obtained by mixing the blood with sulfosalicylic acid. The supernatant was neutralized with ammonium acetate and then screened using Triage. The lower limits of detection of the Triage screening method for PCP, diazepam, benzolyecgonine, methamphetamine, morphine, 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH), phenobarbital, and secobarbital were 50 ng/mL, 900 ng/mL, 1,000 ng/mL, 600 ng/mL, 900 ng/mL, and 900 ng/mL, respectively. The sensitivity of Triage for THC-COOH in deproteinized blood samples was much lower than that in urine samples. No false positive reactions were observed for the 6 classes of the drugs of abuse with the exception of AMP when the blood was decomposed. Phenethylamine, a putrefactive amine, gave positive results for AMP at concentrations over 5,000 ng/mL. The method was applied to 9 hemolyzed blood samples and 3 turbid urine samples from 12 forensic autopsy cases suspected of drug misuse. Among these, 5 were positive for AMP, 1 for OPI, and 4 for BAR. The presence of methamphetamine is only one of the 5, codeine in 1, and phenobarbital in 4 was confirmed by gas chromatography. All 4 samples which were false positive for AMP contained phenethylamine at relatively high concentrations because of moderate to heavy putrefaction. This method, although disadvantageous to test for AMP and THC, is helpful for the forensic toxicologist because any kind of bloody fluid can be tested rapidly with Triage to detect toxic levels of PCP, BZO, COC, OPI, and BAR.
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PMID:Application of the Triage panel for drugs of abuse to forensic blood samples. 869 49


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