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)

PCP is again becoming a popular drug of abuse in the United States, particularly among the young. A variety of medical, psychiatric and pathologic effects make PCP both appealing and profoundly dangerous to naive and chronic drug users. Pharmacologic intervention is helpful in PCP-induced acute intoxication and psychosis. Effective long-term treatment is available in addiction programs.
 ...
PMID:PCP: a dangerous drug. 304 73

As phencyclidine hydrochloride (PCP) has become one of the more frequently abused drugs in the United States, there has been increasing interest in its effect on the fetus and neonate of the pregnant abuser. Two groups of women enrolled in a comprehensive perinatal addiction program were studied: 7 women abused PCP prior to and during pregnancy, and these women were compared to a group of 27 drug-free women. No differences between the two groups were seen in maternal age, gravidity, gestational age or Apgar scores. At birth, there was no difference in birth weight, length, or head circumference between the two groups of neonates. The most characteristic features of the PCP-exposed infants were the sudden outbursts of agitation and rapid changes in level of consciousness, similar to responses described in adults intoxicated with PCP. Scores on the Brazelton Neonatal Behavioral Assessment Scale revealed a significant increase in lability of states and poor consolability in PCP-exposed infants. 3-month scores on the Bayley Scales of Infant Development revealed no significant difference between the two groups of infants.
 ...
PMID:Phencyclidine: effects on the fetus and neonate. 664 70

Patterns of neural degeneration were compared following continuous administration of four drugs of addiction, each of which induces model psychoses in chronic addicts. D-amphetamine (D-Amph), cocaine (Coc), or phencyclidine (PCP) were administered continuously over a 5-day period. Both D-Amph and Coc induced pronounced degeneration in fasciculus retroflexus, but only D-Amph further induced substantial degeneration in striatum. Continuous PCP produced entirely different degeneration largely confined to the posterior entorhinal cortex, ventral dentate gyrus, and cingulate cortex. Methamphetamine (Meth) administered in the very high dose but less prolonged drug regimen often employed in studies of dopamine toxicity induced pronounced degeneration in striatum, but widespread degeneration in many other regions as well. These results indicate that drugs of abuse with psychotomimetic properties induce distinctively different patterns of neural degeneration, a finding with implications for theories of addiction and psychosis. They predict two different anatomical loci for alterations in psychosis: fasciculus retroflexus and ventral parahippocampus and hippocampus.
 ...
PMID:Dissimilar patterns of degeneration in brain following four different addictive stimulants. 828 Aug 52

This article is an exploration of the National Institute on Drug Abuse (NIDA) Technical Review on the role of glutamatergic systems in the development of opiate addiction. The effects of "glutamate antagonist" medications on opioid tolerance and withdrawal are examined. In rodents, mu opioid tolerance can be inhibited by noncompetitive N-methyl D-aspartate (NMDA) receptor antagonists [MK801, dextromethorphan (DM), ketamine, phencyclidine (PCP)], competitive NMDA receptor antagonists (LY274614, NPC17742, LY235959), partial glycine agonists (ACPC), glycine antagonists (ACEA-1328), and nitric oxide synthase (NOS) inhibitors [L-NNA, L-NMMA, methylene blue (MB)]. Similarly, some of the symptoms of opioid withdrawal observed in opioid-dependent rodents also can be inhibited by noncompetitive NMDA receptor antagonists (MK801, DM, ketamine), competitive NMDA receptor antagonists (LY274614), glycine antagonists (felbamate), and NOS inhibitors (L-NNA, L-NMMA, L-NAME, L-NIO, 7-NI, MB). There are some serious toxicological effects associated with the administration of some of the noncompetitive NMDA receptor antagonists in rodent but not in squirrel monkey brain, and some medications induce PCP-like behavioral effects. The medications with the most immediate clinical appeal are those that could be coadministered with methadone to decrease mu opioid tolerance and dependence; they include DM, MB, 7-NI, ACPC, and ACEA-1328.
 ...
PMID:The effects of NMDA receptor antagonists and nitric oxide synthase inhibitors on opioid tolerance and withdrawal. Medication development issues for opiate addiction. 874 52

Phencyclidine (PCP) is a drug that has been widely abused in the past two decades. PCP produces place aversion, but not preference, in the place conditioning test. The present study examined PCP-induced place conditioning behavior in rats treated with PCP repeatedly. In naive rats, PCP (2-8 mg/kg i.p.) dose dependently produced place aversion, but did not produce any effect in rats treated with PCP (10 mg/kg i.p.) for 14 days. indicating that tolerance developed to PCP-induced place aversion on repeated PCP treatment. In rats treated with PCP (10 mg/kg i.p.) for 28 days, PCP (2-8 mg/kg i.p.) dose dependently produced place preference. These findings suggest that some changes in neuronal function induced by the repeated PCP treatment may play an important role in the addiction to this drug.
 ...
PMID:Acute phencyclidine induces aversion, but repeated phencyclidine induces preference in the place conditioning test in rats. 900 5

Seventy-seven college students varying in degree of drug use experience rated the perceived similarities of all possible combinations of 16 drugs classes (cigarettes, other tobacco, alcohol, marijuana, barbiturates, minor and major tranquilizers, amphetamines, amphetamine derivatives, cocaine, heroin, opiates, hallucinogens, inhalants, PCP, anti-depressants). Multi-dimensional scaling (INDSCAL) and network models (PFNET) indicated that abstainers had only one pharmacological category involving sedatives/depressants, and that they attached more importance to whether drugs were licit vs. illicit than to whether they were depressants vs. stimulants. Conceptions became more coherent, differentiated and based on pharmacological properties for more experienced drug users. In line with previous work, groups with greater experience with drugs had more sophisticated conceptions not only about the drugs they had used, but also about drugs they had not used. These findings suggest that early on in drug behavior sophisticated and interrelated concepts are developing that should be taken into account when designing interventions and information campaigns.
Addiction 1997 Jul
PMID:Concepts of drugs: differences in conceptual structure across groups with different levels of drug experience. 929 44

Although the mechanism of action of ibogaine, a hallucinogen that may be useful in the treatment of addiction, remains unknown, receptor binding studies suggest that ibogaine produces its effects via interactions with multiple receptor types. In addition to serotonergic receptors, which have been studied previously with respect to ibogaine, likely candidates include opiate, sigma (sigma), and phencyclidine (PCP) binding sites. In an attempt to determine which of these receptor interactions are involved in the in vivo effects of ibogaine, ligands for sigma, PCP, and opiate receptors were assessed for their ability to substitute for or to antagonize the ibogaine-induced discriminative stimulus (10 mg/kg I.P., 60 min presession) in Fischer-344 rats. Intermediate levels of generalization were observed with the subtype nonselective sigma ligands 3-(3-hydroxyphenyl)-N-(1-propyl)-piperidine [(+)-3-PPP] (69.0%) and 1,3-di(2-tolyl)guanidine (DTG) (73.5%) but not with the sigma1-selective agents (+)-N-allylnormetazocine [(+)-SKF 10,047] and (+)-pentazocine. These findings, along with observations that ibogaine has appreciable affinity for sigma2 receptors, suggest that these receptors may be involved in the ibogaine discriminative stimulus. With regard to opiate receptors, neither morphine, the prototypic mu agonist, nor kappa selective agonists (bremazocine,and U-50488) substituted for ibogaine. However, intermediate levels of generalization were observed with the mixed action opiates (-)-SKF 10,047 (78.9%), (+/-)-pentazocine (73.9%), nalorphine (70.4%), and diprenorphine (75.0%) indicating a potential role for opiate receptors in the ibogaine stimulus. Partial substitution was also observed with naltrexone (55.6%) but not with naloxone or the selective kappa antagonist nor-binaltorphimine (nor-BNI). These agents were largely ineffective as antagonists of the ibogaine cue, although naloxone produced a moderate but statistically significant antagonism (69.8%). In addition, naloxone produced complete antagonism of the ibogaine-appropriate responding elicited by both (-)-SKF 10,047 (19.7%) and nalorphine (25.8%), whereas the ibogaine-appropriate responding produced by diprenorphine was only partially antagonized (44.4%). The latter observations taken together with the finding that both nalorphine (>100 microM) and diprenorphine (30 microM) have extremely low affinity for sigma2 receptors, suggest that the ibogaine-appropriate responding produced by these agents is not mediated by sigma2 receptors. These findings imply that opiate effects may be involved in the ibogaine stimulus. In contrast to sigma2 and opiate receptors, ibogaine's reported interactions with NMDA receptors do not appear to be involved in its discriminative stimulus, as neither PCP nor MK-801 produced a significant level of ibogaine-appropriate responding. Thus, the present study offers evidence that unlike NMDA receptors, both sigma2 and opiate receptors may be involved in the ibogaine discriminative stimulus.
 ...
PMID:The effects of sigma, PCP, and opiate receptor ligands in rats trained with ibogaine as a discriminative stimulus. 947

Place conditioning paradigms are widely used for determining the motivational properties of drugs. Phencyclidine (PCP) has been a common drug of abuse during the past two decades and has a rewarding effect in animals. However, PCP produces place aversion in the conditioned place preference (CPP) task in animals. Here, we report the possible neuronal mechanisms of PCP-induced place aversion and preference in the CPP task in rodents. In naive rats and mice, PCP dose-dependently produced place aversion and PCP had a significant effect at the doses of 4 and 8 mg/kg in rats and mice, respectively. The aversive effect of PCP (4 mg/kg) in rats was significantly attenuated by ritanserin (3 and 10 mg/kg), a serotonin 15-HT2) receptor antagonist whereas the lesion of serotonergic (5-HTergic) neurons by 5,7-dihydroxytryptamine (100 micrograms i.c.v.) and alpha-methyl-rho-tyrosine (AMPT; 100 mg/kg), a tyrosine hydroxylase inhibitor, did not affect the aversive effect of PCP. In rats pretreated with PCP (10 mg/kg/day) for 14 days, tolerance was developed to PCP (4 mg/kg)-induced place aversion. In rats and mice pretreated with PCP (10 mg/kg/day) for 28 days, however, PCP dose-dependently produced place preference but not aversion. The preferred effect of PCP (8 mg/kg) in mice preteated with PCP (10 mg/kg/day for 28 days) was significantly attenuated by AMPT (100 mg/kg) and 6-hydroxydopamine (100 micrograms i.c.v.) a dopaminergic (DAergic) neurotoxin, but not by DSP-4 (30 mg/kg), a noradrenergic neurotoxin and ritanserin. In mice pretreated with methamphetamine (1 mg/kg/day) for 14 days, PCP (8 mg/kg) produced place preference. These findings suggest that 5-HTergic and DAergic systems are involved in the PCP-induced place aversion and preference, respectively, and some changes in the neuronal systems including DAergic systems, induced by repeated PCP treatment play a critical role in the addiction of PCP.
 ...
PMID:Neuronal mechanisms of phencyclidine-induced place aversion and preference in the conditioned place preference task. 981 6

The results of the studies described here support the hypothesis that ibogaine produces its effects via selective interactions with multiple receptors. It appears that 5-HT2A, 5-HT2C, and sigma 2 receptors are involved in mediating the stimulus effects of ibogaine. In addition, opiate receptors may also be involved. In contrast, sigma 1, PCP/MK-801, 5-HT3, and 5-HT1A receptors do not appear to play a major role. Ibogaine's hallucinogenic effects may be explained by its interactions with 5-HT2A and 5-HT2C receptors, while its putative antiaddictive properties may result from its interactions with sigma 2 and opiate receptors. Alternatively, the possibility that ibogaine's hallucinogenic properties underlie its antiaddictive effects, as previously suggested (34), would support a role for 5-HT2 receptors in mediating the reported therapeutic effects of ibogaine. Certainly many questions remain regarding ibogaine's mechanism of action. Although drug discrimination will be useful for answering some of those questions, the true potential of this technique is realized whin it is combined with other techniques. The next few years promise to be fruitful with respect to our understanding of this agent. Reasons supporting this belief include advances in the study of sigma receptors, interest in ibogaine's effects on second messenger systems, and the development of ibogaine congeners such as 18-methoxycoronaridine (35). In conclusion, the aforementioned studies should serve to guide further endeavors. Pertinent questions have been generated: What is the role of sigma receptors in the effects of ibogaine, especially with regard to addiction? How does ibogaine affect opiate neurotransmission? What effects, if any, do the Harmala alkaloids have on addiction phenomena? What is the mechanism of action of harmaline? Can 10-hydroxyibogamine serve as a discriminative stimulus and, if so, what receptor interactions mediate its stimulus effects? Does the ibogaine-trained stimulus generalize to novel agents, including 18-methoxycoronaridine?
 ...
PMID:Drug discrimination studies with ibogaine. 1170 17

Chemical substance abuse has tormented mankind throughout history. A number of chemical approaches have been employed in an attempt to treat chemical addiction. Unfortunately, most of these have proven unsuccessful though several chemical entities have been shown to be moderately effective. The naturally occurring alkaloid ibogaine has been reported to interrupt the cravings for alcohol, cocaine and opiates. Other alkaloids from Tabernanthe iboga, such as ibogamine and tabernanthine, provide insight into the structure activity relationship at the different receptors believed to be involved in addiction. The synthetic iboga alkaloid congener, 18-MC, also shows potential as an anti-addictive agent without the hallucinogenic effects of ibogaine. Additionally, acamprosate, BP 897, GBR12909, lofexidine and memantine have shown promising results in the treatment of addiction. All of these leads provide a start for the medicinal chemist to design anti-addictive agents, since currently no drugs are approved in the U.S. for the treatment of addictions to cocaine, methamphetamine, other stimulants or PCP.
 ...
PMID:A review of chemical agents in the pharmacotherapy of addiction. 1236 79


1 2 3 Next >>