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)

The effects of phencyclidine (PCP) alone and in combination with the CNS depressants, pentobarbital (PB) or ethanol (ETOH), were determined in mice using the inverted screen test and in rats using disruption of milk drinking behavior. The effects of PB and ETOH alone, and in combination, were also determined so that the PCP combinations could be compared to this clinically relevant interaction. These homergic drug interactions were analyzed using the dose-addition model by isobolographic analyses. Most drug combinations resulted in shifts to the left of the dose-effect curves relative to the dose-effect curves for the drugs alone; in no cases were shifts to the right (antagonism) observed. In general, the interactions between PCP and ETOH or PB were quantitatively less (infra-additive) than the interaction between the CNS depressants (dose-additive) when studied in mice. In the rat studies, the interactions between PCP and ETOH or PB were, overall, quantitatively greater (dose-additive or supra-additive) than the ETOH-PB interactions (infra-additive). Since even infra-additive interactions may result in substantially enhanced effects, these results suggest that coabuse of PCP with CNS depressant drugs could produce marked behavioral toxicity.
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PMID:Interactions between phencyclidine and central nervous system depressants evaluated in mice and rats. 362 47

Experiments were conducted to evaluate the degree of phencyclidine (PCP)-like activity associated with the dextro and levo enantiomers of the sigma agonist N-allylnormetazocine (NANM). In chronic spinal dogs, d- and l-NANM generally produced similar physiologic and gross animal behavior effects which included miosis, tachycardia, hyperthermia, increased secretory activity (lacrimation, rhinorrhea and salivation), nystagmus and stereotyped head movements. For these effects, d- and l-NANM were generally equal in potency and both were about 1/10th as potent as PCP. However, the NANM enantiomers could be differentiated on the basis of their effects on nociceptive reflexes. Comparisons of dose-response curves and efficacies demonstrated that d-NANM was more similar to PCP in its effectiveness in depressing the flexor and skin twitch reflexes than was l-NANM. In addition, naltrexone selectively antagonized or reduced only the effects of l-NANM on reflex activity. In intact dogs, d-NANM and PCP, but not l-NANM maintained self-administration behavior under FR15 or FI900 (FR10:S) schedules of reinforcement. This represented the most stereospecific action of the NANM enantiomers. Additionally, l-NANM failed to maintain self-administration behavior, even following pretreatment with naltrexone, thus suggesting that the opiate activity of l-NANM was not responsible for its lack of reinforcing efficacy. Taken together, the data demonstrate that both d- and l-NANM have PCP-like properties, but d-NANM is pharmacologically more equivalent than l-NANM to PCP and l-NANM has additional activity which is not PCP-like.
Drug Alcohol Depend 1986 Oct
PMID:Pharmacologic and reinforcing properties of phencyclidine and the enantiomers of N-allylnormetazocine in the dog. 378 Apr 14

The role of ethanol in phencyclidine-related death and loss of motor co-ordination was studied in male ICR albino mice. LD50s, and ED50s for loss of righting reflex, and for the "rotarod" test were determined for each drug in the presence of various doses of the other. Isobolograms (plots of equieffective dose combinations) of these LD50s and ED50s showed that low doses of ethanol reduced the LD50 of phencyclidine (PCP) by about 20%, while higher doses (1-3 g/kg) of ethanol were without further effect. In contrast to effects on lethality, there was synergism (potentiation) of loss of motor co-ordination. Doses of ethanol above 1 g/kg reduced the ED50 of PCP for loss of righting from about 60 mg/kg to 1-3 mg/kg. Similarly, low doses of PCP (less than 40 mg/kg) reduced the ED50 of ethanol from 3 g/kg to 1 g/kg. There was a slight but consistent synergism between the drugs in the rotarod test over the range of effective doses (0.25-2.0mg/kg PCP and 0.1-1.2 g/kg ethanol). It is concluded that consumption of ethanol does not greatly increase the risk of death from PCP overdose; however the severe adverse effects on motor co-ordination of moderate doses of PCP together with moderate doses of ethanol are greatly potentiated by doses of the other drug. It is estimated that commonly used doses could result in total loss of motor ability, which could explain the prevalence of accidental deaths (especially drowning) when PCP and ethanol have been consumed together.
Alcohol Drug Res
PMID:Toxicity of phencyclidine and ethanol in combination. 383 27

Cyclazocine is a benzomorphan which, in addition to more classical opiate properties, binds to the sigma opiate receptor site. Recently, it has been suggested that the sigma opiate receptor is identical to the binding site responsible for the actions of phencyclidine (PCP). Since the electrophysiological actions of PCP have already been demonstrated on rat cerebellar Purkinje neurons, the effects of cyclazocine were also studied in this system with the goal of comparing the electrophysiological effects of cyclazocine to those of PCP. Cyclazocine inhibited the spontaneous firing rates of Purkinje neurons. These responses were stereospecific and qualitatively appeared similar to the effects of PCP. Antipsychotic drugs, haloperidol and fluphenazine, partially antagonized the actions of cyclazocine, suggesting a catecholaminergic involvement similar to the mechanism proposed for PCP. Unlike PCP, the effects of cyclazocine were also partially reversed by the opiate antagonist, naloxone. Taken together, these results suggest that in the rat cerebellum cyclazocine may be interacting with at least two receptor mechanisms: a naloxone-sensitive opiate site, and a naloxone-insensitive site which might involve catecholaminergic mediation similar to the PCP mechanism of action. The naloxone-sensitive effects of cyclazocine, however, may be related to an interaction of the drug with kappa receptors rather than with the more classical mu or delta opiate mechanisms.
Alcohol Drug Res
PMID:Electrophysiological effects of cyclazocine on rat cerebellar Purkinje neurons: comparison with phencyclidine. 407 70

The repeated administration of phencyclidine (PCP, 72 mg/kg/day) to rats led to physical dependence, as evidenced by a withdrawal syndrome exhibited approx. 24-48 h following suspension of drug. All components of the withdrawal syndrome were suppressed by s.c. injections of PCP (16 mg/kg), (+/-)-N-allylnormetazocine (SKF-10047, 16 mg/kg) and (+)-SKF-10047 (16 mg/kg), but not by injections of saline or (-)-SKF-10047. Moreover, tolerance to the behavioral effects of PCP, as well as cross-tolerance to (+/-)-SKF-10047 and (+)-SKF-10047 were observed. These data indicate that PCP and the sigma opiate SKF-10047 share mechanisms of action, which are mediated by the (+)-isomer of the sigma agonist.
Drug Alcohol Depend 1983 Oct
PMID:Effects of SKF-10047 in the phencyclidine-dependent rat: evidence for common receptor mechanisms. 631 23

Currently, average apparent consumption of alcohol for all persons older than 14 is 10 percent higher than 10 years ago, and is equivalent to about 2.75 gallons of ethanol per person per year. Approximately 10 million adult Americans (i.e., 7 percent of those 18 or older) can be considered problem drinkers. Youthful problem drinkers, aged 14 to 17, are estimated to number more than 3 million and comprise 19 percent of this age group. In addition to the social costs, the economic costs to society as a result of alcohol misuse are substantial--an estimated +49.4 billion in 1977. Ten percent of all deaths in the United States are alcohol-related. Cirrhosis, which is largely attributable to alcohol consumption, ranks among the 10 leading causes of death. Alcohol use also is associated with cancer of the liver, pancreas, esophagus, and mouth. Alcohol consumption during pregnancy is associated with a wide range of possible harmful effects to the fetus--among them decreased birth weight, spontaneous abortion, and physical and mental birth defects. Drug misuse is also an expanding problem. There are some 16 million current marijuana users. The popularity of cocaine continues to increase--over 10 million Americans have tried cocaine at least once and there are an estimated 1 to 2 million current users. Misuse of barbiturates remains a significant problem with at least 1 million persons believed to misuse these drugs and the 30,000 estimated to be addicted to them. In addition, heroin addiction is still considered by many to be the most serious drug problem in the United States. Drug misuse leads to a number of social and health problems. Excessive doses of depressants can result in both physical and psychological dependence. The toll from heroin includes premature death and severe disability, family disruption, and crime committed to maintain the habit. Misuse of hallucinogens often results in emergency room visits. A special problem is the relationship of marijuana to automobile accidents, especially when used in combination with alcohol. While these events are disconcerting, progress has been made. National surveys indicate no changes in peak quantity consumed by teenagers 12 to 17 or in regularity of their drinking, between 1974 and 1978. Alcoholism mortality rates and alcoholic psychosis rates have shown little overall increase between 1950 and 1975. And similar encouraging trends have occurred in drug misuse. Several drug abuse data sources simultaneously have begun to reflect a down turn in use rates. These early indicators must be monitored overtime before conclusions as to their true significance can be evaluated.Nonetheless, the daily use of marijuana by high school seniors dropped from a peak of 10. 7 percent in 1978 to 7.0 percent in 1981. Daily regular cigarette smoking among seniors also declined dramatically-from 28 percent to 10 percent in the same period. The use of the hallucinogenic drug PCP also dropped markedly. Cocaine,heroin and sedative use among high school seniors remained relatively stable in terms of annual and lifetime prevalence, although the use of stimulants rose markedly. Of the 16 categories of drug use analyzed in the recent High School Senior Drug Use Survey, drug use in 15 categories was either stable or was decreasing(the second year of decline since the survey began in 1975).
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PMID:Health promotion: Alcohol and drug misuse prevention. 641 12

A critical appraisal of issues and problems in monitoring urinary phencyclidine (PCP) is presented. Problems may be related to impurities of ingested material and/or metabolites, and methods that are not sensitive enough to detect PCP in the nanogram/ml amounts which may be present in blood or urine. Possible false positives found with some methods are discussed. Most complicated of all is the unpredictable excretion of PCP which can result in negative urines followed by urines which test positive for PCP without necessity of any further ingestion of PCP. A set of guidelines for use in monitoring and interpreting PCP values is included.
Adv Alcohol Subst Abuse 1984
PMID:Critical interpretation of urinary phencyclidine monitoring. 649 33

Rats (N=6) were trained to discriminate 3.0 mg/kg i.p. phencyclidine (PCP) from saline in a 2-lever fixed-ratio 32 operant discrimination procedure for food presentation. Generalization tests were conducted with other doses of PCP as well as with various doses of the stereoisomers of dioxadrol. Dose-dependent PCP-like discriminative stimulus effects were obtained with dexoxadrol but not with levoxadrol, however overall rates of responding were decreased to a comparable extent by 30 mg/kg of both compounds. PCP was 3.6 times more potent than dexoxadrol in producing stimulus control of responding. These data provide some evidence for stereoselectivity of action for dioxadrol, however nonPCP-like effects of levoxadrol are present at doses only 3 times greater than those doses of dexoxadrol that result in PCP-lever responding. Therefore, absolute stereospecificity beyond 3-fold cannot be demonstrated by these data.
Subst Alcohol Actions Misuse
PMID:Phencyclidine-like discriminative stimulus properties of the stereoisomers of dioxadrol. 654 61

In view of potential ability of calcium entry blockers to affect Ca2+ fluxes in neurons, the effects of nisoldipine on phencyclidine (PCP) and apomorphine (APO) induced stereotyped behavior have been examined in 3 and 4 week old rats. The rats (3 and 4 weeks old) were pretreated with either 0.2 ml of saline + ethanol mixture (10:1 v/v) or nisoldipine (25 mg/kg) i.p., 5 min before the i.p. administration of PCP (5 mg/kg) or APO (10 mg/kg). While nisoldipine pretreatment significantly blocked the PCP induced stereotypy in 3 and 4 week old rats, the APO induced stereotypy was not altered. These preliminary data suggest that nisoldipine specifically blocks PCP induced stereotypy probably by antagonizing it effects at the presynaptic level. The significance of this finding in relation to mechanism of action of PCP and calcium entry blockers is discussed.
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PMID:The influence of nisoldipine--a "calcium entry blocker" on drug induced stereotyped behavior in rats. 668 13

Twenty-three blood constituents were analyzed in rats chronically injected with phencyclidine (PCP, angel dust). After receiving three injections weekly for an average of 9 months the only analyte to significantly change was creatine phosphokinase (CPK), which showed a threefold elevation over the saline injected controls.
Subst Alcohol Actions Misuse 1983
PMID:Effect of chronic phencyclidine administration upon blood biochemical profiles in rats. 668 96


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