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Current Opinion in Pharmacology Feb 2005Phencyclidine has attracted the attention of neuroscientists for many years because of its ability to produce, in humans, a range of symptoms remarkably similar to those... (Review)
Review
Phencyclidine has attracted the attention of neuroscientists for many years because of its ability to produce, in humans, a range of symptoms remarkably similar to those of patients suffering from schizophrenia. The main action of phencyclidine is as a non-competitive antagonist of the NMDA class of glutamate receptor. In the past few years, dramatic advances have been made in our understanding of the neuroanatomical and pathological basis of schizophrenia. In turn, these have allowed assessment of the ability of phencyclidine to produce equivalent changes in the rodent CNS. It has now become clear that chronic intermittent low doses of phencyclidine produce a pattern of metabolic and neurochemical changes in the rodent brain that mirror those observed in the brains of schizophrenic patients with impressive precision. This should be of enormous benefit in the search for new anti-psychotic drugs with improved efficacy against the full range of schizophrenic symptoms.
Topics: Animals; Hallucinogens; Humans; Models, Biological; Phencyclidine; Phencyclidine Abuse; Receptors, N-Methyl-D-Aspartate; Schizophrenia
PubMed: 15661633
DOI: 10.1016/j.coph.2004.08.008 -
Drug Metabolism and Disposition: the... 1987The phencyclidine iminium ion (PCP-Im+), a potentially reactive 2,3,4,5-tetrahydropyridinium species, is formed by the cytochrome(s) P-450-catalyzed alpha-carbon...
The phencyclidine iminium ion (PCP-Im+), a potentially reactive 2,3,4,5-tetrahydropyridinium species, is formed by the cytochrome(s) P-450-catalyzed alpha-carbon oxidation of phencyclidine (PCP), a commonly abused psychotomimetic agent. Incubation of PCP-Im+ with liver microsomes obtained from phenobarbital-induced rabbits resulted in over 50% loss of microsomal N-demethylase activity and 30% reduction in cytochrome(s) P-450 content. These effects were concentration-dependent, irreversible, and exhibited pseudo-first order kinetics, characteristics of a mechanism-based enzyme inactivation process. Incubation of 3H-PCP-Im+ with liver microsomes resulted in covalent binding of radioactive material to macromolecules by a process that also was NADPH-dependent. PCP-Im+ was metabolized by liver microsomes in the presence of NADPH and this metabolism was inhibited by SKF 525A and carbon monoxide. HPLC analysis has led to the preliminary characterization of an oxidized metabolite of PCP-Im+ which also is formed from PCP. These results support the proposal that this tetrahydropyridinium metabolite of PCP is biotransformed in a cytochrome(s) P-450-catalyzed reaction to form reactive species capable of covalent interactions with biomacromolecules.
Topics: Animals; Biotransformation; Cytochrome P-450 Enzyme Inhibitors; In Vitro Techniques; Male; Microsomes, Liver; NADP; Oxidoreductases, N-Demethylating; Phencyclidine; Rabbits
PubMed: 2888621
DOI: No ID Found -
Proceedings of the National Academy of... Jan 1986Phencylidine (PCP) is a major drug of abuse in the United States. It produces a toxic confusional psychosis in man. We show here that nanomolar to micromolar...
Phencylidine (PCP) is a major drug of abuse in the United States. It produces a toxic confusional psychosis in man. We show here that nanomolar to micromolar concentrations of PCP and behaviorally active congeners selectively block voltage-regulated noninactivating (or very slowly inactivating) presynaptic K channels in the brain. The rank order of potency for blockage of these K channels parallels both the relative ability of these agents to produce characteristic behavioral deficits in rats and their ability to displace [3H]PCP from its high-affinity binding sites in brain. In view of the enhanced voltage-gated Ca influx that would be expected to accompany blockage of presynaptic K channels, this mechanism could explain the excessive neurotransmitter release that is characteristic of PCP intoxication.
Topics: Animals; Brain; Calcium; Cell Membrane Permeability; Dose-Response Relationship, Drug; Ion Channels; Phencyclidine; Potassium; Radioisotopes; Rats; Rubidium; Synaptosomes
PubMed: 2417237
DOI: 10.1073/pnas.83.1.189 -
JACEP Feb 1979Phencyclidine (PCP) is a potent sympathomimetic and hallucinogenic dissociative anesthetic agent. As an abused street drug, it is most often smoked, thus allowing the...
Phencyclidine (PCP) is a potent sympathomimetic and hallucinogenic dissociative anesthetic agent. As an abused street drug, it is most often smoked, thus allowing the user to titrate the dose. The clinical signs of PCP intoxication can be viewed in three dose-related stages, but waxing and waning of signs through the three stages is not uncommon. Treatment protocols for each stage address drug therapy and both clinical and psychological supportive measures.
Topics: Adolescent; Behavior; Classification; Diazepam; Emergencies; Female; Humans; Intubation, Intratracheal; Male; Middle Aged; Phencyclidine; Propranolol; Respiration
PubMed: 439546
DOI: 10.1016/s0361-1124(79)80040-4 -
Biochimie Sep 1985
Topics: Adolescent; Adult; Behavior; Child; Humans; Illicit Drugs; Phencyclidine; Receptors, Neurotransmitter; Receptors, Phencyclidine; Substance-Related Disorders; United States; Violence
PubMed: 3002498
DOI: 10.1016/s0300-9084(85)80279-0 -
Biomedical Mass Spectrometry Feb 1978Phencyclidine was determined by gas chromatography selected ion monitoring in six dogs and seven monkeys. Aliquots of venous blood were taken over 4 h in the monkey...
Phencyclidine was determined by gas chromatography selected ion monitoring in six dogs and seven monkeys. Aliquots of venous blood were taken over 4 h in the monkey after 1.1 mg kg-1 and over 24 h in the dog after 1.0 mg kg-1 of phencyclidine i.v. Pentadeuterated phencyclidine was used as the internal standard. In the electron impact mode the most abundant fragments in the mass spectrum of phencyclidine were m/e 91 and 200, and 96 and 205 in the [2H5]phencyclidine spectrum. These fragments were used to quantitate the amount of phencyclidine present. In both species, a complex exponential decline of plasma phencyclidine was found in most animals that fit a two compartment open model. In monkeys, the mean half-life (beta phase) was 2.36 h and in the dog it was 2.86 h. Compared with the monkey, the dog considerable emergence delirium. The two species had rather different pharmacokinetics which may be relevant to the observed differences in degree of anesthesia and recovery.
Topics: Animals; Chromatography, Gas; Dogs; Gas Chromatography-Mass Spectrometry; Haplorhini; Kinetics; Mass Spectrometry; Phencyclidine
PubMed: 415768
DOI: 10.1002/bms.1200050203 -
Journal of Forensic Sciences Jul 1981Phencyclidine (PCP) can be detected in human hair wih commercially available radioimmunoassay regents. hair samples of all subjects admitting PCP use were positive,...
Phencyclidine (PCP) can be detected in human hair wih commercially available radioimmunoassay regents. hair samples of all subjects admitting PCP use were positive, while thin-layer chromatographic urine analyses were positive in only one of seven cases. Presumably the drug is incorporated into the hair during periods of drug use and then retained in that particular section of the hair for its lifetime. Earlier results in this laboratory in a more detailed study of opiate retention in hair indicated not only that nanogram levels of the drug could be measured in a single strand of hair, but also that sectional analysis of the strand could indicate the time of drug use. The PCP results again suggest that the hair sample could serve as a valuable tool in the determination of drug abuse histories. The sample accessibility and stability and the long-term retention of the drugs in hair exemplify the potential advantages of the hair sample over the body fluid sample.
Topics: Hair; Humans; Phencyclidine; Radioimmunoassay
PubMed: 7252470
DOI: No ID Found -
European Neurology 2001
Topics: Administration, Inhalation; Amaurosis Fugax; Brain; Diagnosis, Differential; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Phencyclidine; Phencyclidine Abuse
PubMed: 11528160
DOI: 10.1159/000050772 -
Life Sciences Jun 1986The dissociative anaesthetics, phencyclidine and ketamine, block excitation of central neurones by N-methylaspartate. Using the technique of microelectrophoresis on rat...
The dissociative anaesthetics, phencyclidine and ketamine, block excitation of central neurones by N-methylaspartate. Using the technique of microelectrophoresis on rat spinal neurones in vivo Metaphit, a phencyclidine receptor acylating agent, was tested to see whether it would antagonise this effect of dissociative anaesthetics. The predominant effect of Metaphit was, however, to reduce N-methylaspartate induced excitation. It is concluded that Metaphit has mixed agonist/antagonist effects at the phencyclidine receptor.
Topics: Action Potentials; Animals; Aspartic Acid; Depression, Chemical; Drug Interactions; Kainic Acid; Ketamine; N-Methylaspartate; Neurons; Oxadiazoles; Phencyclidine; Quisqualic Acid; Rats; Receptors, Opioid; Receptors, sigma; Spinal Cord
PubMed: 3014248
DOI: 10.1016/0024-3205(86)90614-4 -
Postgraduate Medicine Nov 1980Phencyclidine (PCP) is a dissociative anesthetic whose abuse is a growing problem. Historically, its effects have been considered remarkably like those of the...
Phencyclidine (PCP) is a dissociative anesthetic whose abuse is a growing problem. Historically, its effects have been considered remarkably like those of the schizophrenic state, but in vitro and in vivo neuropharmacologic data are somewhat inconsistent with the dopaminergic hypothesis of schizophrenia. The physiologic and psychiatric manifestations of PCP intoxication are diverse and somewhat dose dependent. Urine acidification may hasten drug excretion.
Topics: Humans; Nervous System; Phencyclidine; Phencyclidine Abuse
PubMed: 7433300
DOI: 10.1080/00325481.1980.11715603