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)

Use of phencyclidine is a diverse phenomenon with wide variations in both the amount taken and the frequency of use. There is a large group of persons who have tried PCP once or twice and discontinued using. One of the key distinctions pointed out by this exploratory study relates to the feelings of control persons have over the effects of the drug. The PCP user who is not bothered by the lack of control is more likely to feel good and party with others when using and is more likely to have high use patterns. Feelings of control over the effects of PCP indicate an important individual difference in understanding reactions to PCP use and further research should systematically examine this phenomenon. There has been a discrepancy between our conceptions of PCP use and the actual patterns of use found in the United States. It appears that at this time most persons in the drug abuse field are willing to accept the fact that PCP is a drug of choice among young people and that some as yet unspecified proportion of users is able to use PCP and avoid major problems. While there remains much speculation about the motivation for use and the effects of such use, it would apper that we are ready to engage in research which systematically looks at the spectrum of users.
NIDA Res Monogr 1978 Aug
PMID:Patterns of phencyclidine use. 10 67

Electrophilic and photoactivated agents have proven to be useful as receptor-selective irreversible probes. These compounds are generally derivatives of selected ligands that may be chemically modified in such a way as to retain high receptor affinity and selectivity while permitting covalent bonding to the receptor protein. The receptor systems described in this chapter are associated with a variety of classes of abused drugs. These irreversible agents are allowing the isolation and purification of these drug receptors to improve our understanding of their physiological and pharmacological properties and to aid us in better design of agents with therapeutic value without abuse or physical dependence liability. In the opioid field, beta-FNA and SUPERFIT have been successfully used to elucidate structure and function of the mu-, kappa-, and delta-receptors, respectively. Recently, the delta- and kappa-subtype selective irreversible ligands naltrindol and UPHIT have been introduced for receptor subtype studies that are designed to further clarify the physiological function of these sites. The PCP recognition site on the NMDA receptor complex and the sigma receptors have been characterized in part by the use of irreversible agents. These receptors, although sharing similar pharmacological properties, are clearly different systems and the irreversible agents described will allow their further characterization. The central-type benzodiazepine receptors have been labeled with irreversible agents; and, now, receptor subsites that differentially recognize beta-carbolines and benzodiazepines have been discovered through studies using a beta-carboline photoaffinity probe. The associated chloride ionophore has been studied with electrophilic irreversible ligands, as well as the pharmacologically distinct peripheral-type benzodiazepine receptors. Physiological function of the latter receptor system has been implicated through the photoaffinity ligand PK 14105, which is highly selective for these sites. Receptor subtype selective irreversible ligands also have been prepared for both the dopamine and sertonin receptors systems in hopes of clarifying their physiological roles in the CNS. It is clear that more selective irreversible compounds with higher affinity will continue to be in demand for further receptor characterization. In addition, radioligands with higher specific activity will continue to be important for molecular weight determination of receptor proteins and autoradiographic studies key to neuroanatomical localization of these sites.
NIDA Res Monogr 1991
PMID:Irreversible ligands as probes for drug receptors. 166 79

Quantitative autoradiographic distribution patterns of sigma/PCP and NMDA receptors show striking similarities but not in all brain areas. We have identified an endogenous ligand of brain PCP receptors which noncompetitively antagonizes NMDA-induced neurotransmitter release from brain slices. These data support the concept that the sigma/PCP receptor ligands may exert their unique behavioral effects by indirect modulation of NMDA-mediated transmission.
NIDA Res Monogr 1986
PMID:Modulation of brain NMDA receptors: common mechanism of sigma/PCP receptors and their exogenous and endogenous ligands. 282 62

Using preparative HPLC, Sephadex G-25 and analytic HPLC, we obtained an active peak inhibiting (3H) PCP receptor binding, with a molecular weight of 3,000 daltons. Another isolation process included acetic acid extraction, Toyopearl HW gel filtration, Sephadex G-10 chromatography and analytic HPLC. An active peak was also observed, which was consistent with that from the first isolation process.
NIDA Res Monogr 1986
PMID:An endogenous ligand for phencyclidine receptors: isolated from human brains. 282 63

A fraction which potently and specifically competed with 3H-PCP binding to rat membranes was isolated from human CSF. This substance ran just before the salts in Sephadex G-25 column and was eluted with low concentrations of acetonitrile in reverse phase HPLC, predicating that it may be a small hydrophilic compound with a MW. of less than 1,000 daltons.
NIDA Res Monogr 1986
PMID:An endogenous ligand from human CSE for the phencyclidine receptor. 282 64

Radio-binding assay, bioassay and HPLC detection were used to observe the antagonistic effects of dextrorphan on PCP's actions. Dextrorphan displayed high affinity to PCP receptors and it had weak PCP-like bioactivity, but could antagonize PCP's action dose-dependently in vitro and shift the dose-response curve to the right. PCP increased the contents of norepinephrine in bath medium, which was reversed by dextrorphan. Thus, the results suggest that dextrorphan is a partial antagonist for PCP receptors.
NIDA Res Monogr 1986
PMID:Dextrorphan: an antagonist for phencyclidine receptor. 282 65

1-[1-(3-Hydroxyphenyl)cyclohexyl]piperidine (PCP-3-OH) is one of the most potent analogs of phencyclidine (PCP). In the present study we describe the binding properties of 3H-PCP-3-OH to guinea pig brain membranes. Scatchard analysis of saturation binding studies revealed the existence of high (0.44nM) and low (17nM) affinity binding components. High affinity binding sites were completely blocked in the presence of (+)SKF 10047 (50nM). In competition studies PCP analogs compete for 3H-PCP-3-OH specific binding in a monophasic manner whereas psychotomimetic opioid ligands compete for this binding in a biphasic manner. Results from both saturation and competition experiments suggest the existence of a common high affinity binding site for psychotomimetic opioid ligands and PCP analogs and a low affinity binding component primarily for phencyclidines.
NIDA Res Monogr 1986
PMID:High and low affinity psychotomimetic opioid binding sites: characterization by a novel 3H-PCP-analog. 282 67

The low energy conformation of MK801. (+)-N-allyl-N-normetazocine, dexoxadrol, etoxadrol and ketamine was found to possess the unique pharmacophore geometry of a PCP pharmacophore hypothesis recently reported by Carroll et al. (1988). Moreover, the union of the volumes of these compounds in their proposed receptor bound conformation locked together such that equivalent groups were superimposed showed that none of the compounds extended into the binding site volume above and below the aromatic ring and along the nitrogen vector.
NIDA Res Monogr 1988
PMID:Phencyclidine (PCP) and phencyclidine-like compounds: a molecular graphics-molecular mechanics study. 285 51

This discussion has highlighted only some of the areas of behavioral pharmacology research with PCP, focusing largely on studies in our laboratories. Some of the areas touched upon lightly have been much more extensively investigated (e.g., PCP-like properties of psychotomimetic opioids). Some areas, such as the search for a PCP antagonist, have been studied with relatively little success so far. Two other areas, among many that are worthy of mention, are the extensive series of studies of the effects of PCP on complex learning procedures, starting with the studies by Moerschbaecher and Thompson (1980a, Moerschbaecher and Thompson 1980b), and an elegant series of studies on the determinants of oral PCP self-administration, beginning with the study by Carroll and Meisch (1980). Much progress has been made on the clinical implications of behavioral research with PCP, and we are in a much better position to respond effectively to this public health problem than we were when it emerged, only a little over 10 years ago. The impetus behind PCP research has come from two directions--from the emergence of PCP as a drug of abuse with the pressing practical questions raised by this epidemic, and from the potential that PCP research has for a fuller understanding of the brain and behavior. Although this discussion has focused on the former, progress toward the latter goal has been equally, if not more, substantial, and may have long-term health implications far beyond those presented by problems of PCP abuse.
NIDA Res Monogr 1986
PMID:Clinical implications of behavioral pharmacology research on phencyclidine. 308 31

These cases illustrate some of the complex issues associated with PCP-related litigation. The concept that malice is implied when an experienced drug user commits a crime while under the influence of the drug is not held in most states, at the present time. The authors have now reviewed in detail four cases of unexpected death following the use of neck holds in PCP-intoxicated individuals. In all of the cases, multiple carotid compression holds had been attempted, according to the history. Skin abrasions, hemorrhage into the soft tissues of the neck, and fractures of the hyoid bone and thyroid cartilage provide structural evidence of the application of substantial force to the neck. On autopsy, there has been no evidence of lethal injuries to the bronchial tree, brain, or heart. Drugs related to PCP are known to alter the carotid sinus reflex. Mechanical stimulation of the carotid sinus in the neck normally results in a slowing of heart rate and a decrease in blood pressure. Carotid sinus stimulation, coupled with the effects of PCP on blood vessels, might result in a marked fall in the blood pressure that could lead, ultimately, to death. Individuals intoxicated with PCP may be at a higher risk to complications of carotid compression neck holds. Hence, additional cases would be expected to become medicolegal issues.
NIDA Res Monogr 1986
PMID:Legal issues associated with PCP abuse--the role of the forensic expert. 308 37


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