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

Dose-frequency curves of toxic effects of a substance A were evaluated in the absence and in the presence of a fixed dose of a second substance B. Data were fitted by the curve-fitting program ALLFIT. Observed combined frequencies of A + B were compared statistically with the expected frequencies of additivity and (or) independence by the phi 2-square goodness-of-fit test. The theoretical dose-frequency curves expected for an additive response were obtained by a solely graphical procedure and the theoretical curves for independent effects were calculated from the effects of B and A at certain doses. In rotarod tests with trained mice, the combined deteriorating effect of ethanol and benzodiazepines were significantly over-additive. However, their lethal interaction appeared underadditive in mice. The lethal underadditive interaction of ethanol and phencyclidine (PCP) can be ascribed largely to independent actions of these compounds. Loss of righting reflex was additively enhanced by PCP, whereas PCP overadditively enhanced the effect of ethanol. The insecticidal action of the cholinesterase inhibitors malathion and parathion appeared additive and significantly different from independent interaction. A comparison of results from dose-response curves with isoboles showed good agreement. The method appears as an attractive alternative or as a complementary procedure to the isobolographic analysis. Combination experiments as described can be carried out and evaluated rather simply, with a minimum of expenditure and a maximum of information.
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PMID:Evaluation of experimental combined toxicity by use of dose-frequency curves: comparison with theoretical additivity as well as independence. 207 26

Phencyclidine (PCP) binds with high affinity to the ion channel associated with the NMDA receptor. The binding of the PCP receptor-specific ligand TCP is greatly reduced at temperatures between 2 degrees C and 6 degrees C, at which the plasma membrane is in a rigid state. However, membrane rigidity alone does not appear to cause the reduced TCP binding, since the membrane fluidizing agent A2C did not increase TCP binding at 4 degrees C; instead, it decreased binding at 21 degrees C. This inhibitory effect of A2C on TCP binding was dose dependent and was highly correlated with A2C-induced increases in membrane fluidity. The IC50 of A2C inhibition was 8.9 mM, with a pseudo-Hill coefficient of -0.24. Scatchard analysis demonstrated that this effect was the result of an increase in the apparent KD of [3H]TCP for the PCP receptor, with no effect on the Bmax. These results suggest that the function of the NMDA-PCP receptor complex is impaired by increases in membrane fluidity. These findings may be pharmacologically relevant in understanding the mechanism of action of such agents as general anesthetics and ethanol, which cause increases in plasma membrane fluidity.
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PMID:Effects of membrane fluidity on [3H]TCP binding to PCP receptors. 217 11

The potency of general anesthetics from different chemical classes was tested after pretreatment with subanesthetic doses of noncompetitive N-methyl-D-aspartate (NMDA) antagonists in mice. Changes in general anesthetic potency were assessed by determination of alteration of duration of loss of righting reflex for ethanol and pentobarbital and changes in the minimum alveolar concentration (MAC) for the volatile anesthetics, halothane and diethyl ether. The ability of the noncompetitive NMDA antagonists, MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclo-hepten-5,10-imine ], phencyclidine (PCP) and ketamine, to increase the potency of general anesthetics paralleled their potency as NMDA antagonists and their affinity for the PCP receptor site of the NMDA receptor-ionophore complex (MK-801 greater than PCP greater than ketamine). These results indicate that block of central NMDA receptors may contribute to the production of anesthesia by a variety of agents.
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PMID:The noncompetitive N-methyl-D-aspartate antagonists, MK-801, phencyclidine and ketamine, increase the potency of general anesthetics. 219 Feb 39

In this review phencyclidine and related arylcyclohexylamines and hallucinogens, using LSD as the prototype, are considered as two distinct classes of abused drugs. Within these classes drugs that are found on the street are discussed, and a current epidemiological summary is provided. The abuse liability and dependence potential of these drugs are evaluated by considering four major determinants of their abuse. First, is the ability of a drug to function as a positive reinforcer and increase the probability of operant behavior leading to its delivery. Animal data describing the reinforcing effects of PCP are reviewed with respect to the influence of variables controlling drug-reinforced behavior; however, there are no animal models of hallucinogen-reinforced behavior. Several methods of quantifying reinforcing efficacy are discussed. A second determinant is the subjective effects of the respective drugs. These effects are described and compared across drugs based on clinical reports in humans and drug discrimination studies in animals. A third determinant is the behavioral and physiological toxicity that results from acute and chronic use of these drugs. Clinical reports and results of sensitive tests that have been developed for laboratory animals are reviewed. A fourth determinant is the dependence potential that exists with these drugs, measured by tolerance development and the extent to which behavioral and physiological disturbances occur when drug use is terminated.
Adv Alcohol Subst Abuse 1990
PMID:PCP and hallucinogens. 219 84

A survey of 104 deaths involving phencyclidine (PCP) occurring from 1981 through 1986 in metropolitan St. Louis, Missouri, is presented. Four black males (22-33 yr) died from fatal PCP intoxication. PCP was detected in an additional 100 deaths: 81 homicides, 13 suicides, and 6 accidental deaths. Seventy-five of these deaths were homicides of Black males (mean age 27 years) typically dying from gunshot wounds, 64 cases. In 50% of deaths where PCP was detected, other drugs were co-administered: ethanol (35%) and cocaine (20%) being the most common mixtures. A dramatic continuous increase in PCP abuse from 1984 through 1986 was demonstrated by drug abuse indicator data: treatment admissions, emergency room episodes, police exhibits, and driving under the influence of PCP arrests. Increased abuse of PCP in St. Louis has been associated with increased medical emergencies and violence against persons.
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PMID:Phencyclidine and violent deaths in St. Louis, Missouri: a survey of medical examiners' cases from 1977 through 1986. 228 25

Measurements of calcium uptake and cyclic GMP production by cerebellar granule cells grown in primary culture demonstrated that ethanol preferentially inhibited N-methyl-D-aspartate (NMDA) receptor-gated cation channel function. Concentrations of ethanol as low as 10 mM inhibited NMDA-stimulated Ca2+ uptake by greater than 30%, and ethanol also inhibited NMDA-stimulated (Ca2+-dependent) cyclic GMP accumulation in a similar, dose-dependent manner. Responses to kainate were significantly less sensitive to ethanol. Studies using various concentrations of NMDA, as well as phencyclidine (PCP) and glycine, suggested that ethanol affected the "coagonist" binding site of the NMDA receptor-channel complex, rather than the PCP recognition site.
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PMID:N-methyl-D-aspartate receptors and ethanol: inhibition of calcium flux and cyclic GMP production. 254 53

Blood or urine specimens from nearly 600 fatally injured drivers in two Los Angeles County studies were analyzed for the presence of alcohol and other drugs of abuse, including PCP, cocaine, opiates and marijuana. The results of the preliminary study indicate that 65 out of 102 fatally injured drivers had used alcohol and/or another drug of abuse - 34 had used alcohol only, 12 had used one or more other drug(s) of abuse, and 19 had used alcohol in combination with another drug of abuse. The results of the larger follow-up study, begun a year later, indicate a continued high level of both alcohol use (41.5%) and marijuana use (19%) with moderate cocaine usage (8%) and low levels (less than 2%) of barbiturate and PCP usage.
Drug Alcohol Depend 1989 Apr
PMID:Drugs of abuse found in fatally injured drivers in Los Angeles County. 270 25

Water-deprived rats were given daily opportunities (2.0-hr sessions) to take water or a sweet solution (20% or 24% sugar-water). After stable intakes of each fluid were achieved, the effects of phencyclidine hydrochloride (PCP), delta-9-tetrahydrocannabinol (THC), ethanol (E), and morphine (M) on intakes were tested. PCP, THC, and M all enhanced intake of the sweet solution, while E produced varying effects across doses tested. With other rats, nearly the same procedure was used except that the test solution presented with water was 0.9% sodium chloride. Doses of PCP enhanced intake of the salty solution. These data, combined with the data from similar studies of the effects of opioids and benzodiazepines, indicate that a wide variety of agents that are self-administered also modify intake of ingesta.
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PMID:PCP, THC, ethanol, and morphine and consumption of palatable solutions. 285 70

The effects of the stereoisomers of the prototypic sigma agonist N-allylnormetazocine were evaluated in squirrel monkeys trained to respond on an electric shock titration schedule. The monkeys responded on a fixed-ratio schedule to decrease the level of shock delivered to their tails. The effects of the isomers were compared to the effects of phencyclidine and morphine administered alone and also in combination with a rate-suppressing dose of morphine. Morphine increased the level at which shock was maintained without decreasing rates of responding in the presence of shock. Both the (+)-isomer and PCP produced increases in the levels at which the monkeys maintained the shock, but only in some animals. The (-)-isomer of N-allylnormetazocine resulted in either decreases or no effect on the level at which the monkeys maintained the shock. The isomers were equipotent in decreasing response rates. When tested in combination with morphine, only the (-)-isomer antagonized the shock-level increasing effects of morphine. Thus, the isomers had similar effects on response rates but the (+)-isomer, like PCP, was more effective in increasing the level at which the monkeys maintained electric shock, while only the (-)-isomer was effective as a morphine antagonist. These results suggest analgesic-like effects for the (+)-isomer of N-allylnormetazocine and substantiate the opiate-antagonist properties of the (-)-isomer.
Alcohol Drug Res 1987
PMID:The effects of N-allylnormetazocine on electric shock titration in squirrel monkeys. 303 Mar 39

Cannabinoid use was studied in a nonspecific population of postmortem urine specimens in the State of Maryland. Of 500 sequential specimens screened for cannabinoids by enzyme multiplied immunoassay EMIT, 63 (13%) were initially positive and 58 (12%) were confirmed positive (92%). It was observed that geographic location and race did not correlate with cannabinoid prevalence. Cannabinoid use was observed to be strongly age related, with peak use by the 21- to 25-year-old age group where 22% of the cases were positive. Use of cannabinoids was also closely linked to homicides, which represented nearly half of the positive cases but only 13% of the total cases. When comparing manner of death, the greatest percent of confirmed positives was seen in homicide (26%) and drug-related (17%) deaths. The incidence of cannabinoid use was found to be more than 3 times as great in drug-related (17%) as compared to natural deaths (5%). The percent of cannabinoid-positive cases from vehicle-related accidents was low (6%) and that from nonvehicle-related accidents somewhat higher (10%). Other drugs appeared in cannabinoid-positive cases. Most prevalent was ethanol N = 18, followed by morphine (from heroin, N = 11), quinine N = 11, and cocaine N = 11. Phencyclidine (PCP) occurred twice and several other drugs were reported only once. Of the 25 homicide cases screened for drugs, 64% were positive for some drug including ethyl alcohol. Thus it appears that a high percentage of homicide cases are drug related. Males greatly outnumbered females (56:2) in positive cases, but the number of female specimens received was small.
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PMID:Incidence of cannabinoids in medical examiner urine specimens. 268 24


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