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Clinical Toxicology 1976The results of the animal experiment demonstrate that oxidative hydroxylation is the major mode of metabolism of phencyclidine. It is evident that this process takes...
The results of the animal experiment demonstrate that oxidative hydroxylation is the major mode of metabolism of phencyclidine. It is evident that this process takes place in all three rings of the molecule. Hydroxylation of the piperidyl moiety probably also accounts for the formation of the N-dealkylated metabolites. Metabolism of phencyclidine in humans appears, at least in part, to be similar to that in the rat. Hydroxylation is still the principal mode in the case of humans though of a lesser extent. Metabolites hydroxylated in the phenyl moiety as well as dihydroxy derivatives of phencyclidine have so far not been observed in humans. Furthermore, most of the monohydroxy metabolites exist as conjugates in the human urine. It should also be pointed out that no metabolites have yet been detected in human blood samples.
Topics: Animals; Chromatography, Gas; Hydroxylation; Phencyclidine; Rats
PubMed: 975754
DOI: 10.3109/15563657608988160 -
Pharmazie in Unserer Zeit Feb 1994
Review
Topics: Animals; Designer Drugs; Humans; Phencyclidine
PubMed: 8159775
DOI: 10.1002/pauz.19940230129 -
Archives of Neurology May 1982
Topics: Adult; Diagnosis; Humans; Male; Methods; Phencyclidine
PubMed: 7073558
DOI: 10.1001/archneur.1982.00510170058019 -
Clinical Toxicology 1976This study was performed to provide knowledge of the tissue distribution of phencyclidine and has demonstrated the lipophilic nature of the drug. The distribution of...
This study was performed to provide knowledge of the tissue distribution of phencyclidine and has demonstrated the lipophilic nature of the drug. The distribution of phencyclidine in blood, brain, and adipose tissue of rats has been determined at various time intervals during a 48-hr period. The affinity of phencyclidine for adipose tissue and the demonstration of the presence of this drug in brain tissue long after it is no longer detectable in blood provides some correlation between the tissue distribution of phencyclidine and its clinical manifestations occuring 24-48 hr after administration.
Topics: Adipose Tissue; Animals; Chromatography, Gas; Phencyclidine; Rats; Time Factors
PubMed: 975753
DOI: 10.3109/15563657608988159 -
Psychopharmacology 1986The amnesic action of phencyclidine (PCP) was investigated in mice using a passive avoidance- and escape-learning method. PCP (10-30 mg/kg) administered immediately...
The amnesic action of phencyclidine (PCP) was investigated in mice using a passive avoidance- and escape-learning method. PCP (10-30 mg/kg) administered immediately after the training test dose-dependently shortened and prolonged the step-down latency and escape latency, respectively in the retention test. There was a significant inverse relationship between the step-down and escape latencies, indicating that PCP had induced amnesia. The amnesic actions of PCP were retrograde, being observed when mice were given PCP within 10 min but not more than 30 min after the training test. The amnesic effects of PCP on both variables were antagonized significantly by physostigmine and naloxone, whereas cyproheptadine and haloperidol had no effect. None of these drugs by themselves affected passive avoidance- or escape-learning performance. These results suggest that the retrograde amnesic actions of PCP were produced via either the cholinergic or the opioidergic systems or both, but not through the serotonergic and the dopaminergic systems.
Topics: Amnesia; Amnesia, Retrograde; Animals; Avoidance Learning; Brain; Cholinergic Fibers; Cyproheptadine; Endorphins; Male; Mice; Phencyclidine; Physostigmine; Retention, Psychology
PubMed: 3088659
DOI: 10.1007/BF00174370 -
NIDA Research Monograph 1988The low energy conformation of MK801. (+)-N-allyl-N-normetazocine, dexoxadrol, etoxadrol and ketamine was found to possess the unique pharmacophore geometry of a PCP... (Review)
Review
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.
Topics: Animals; Dibenzocycloheptenes; Dizocilpine Maleate; Molecular Conformation; Molecular Structure; Phencyclidine; Receptors, Neurotransmitter; Receptors, Phencyclidine; Structure-Activity Relationship
PubMed: 2855851
DOI: No ID Found -
Mini Reviews in Medicinal Chemistry Jan 2014Phencyclidine (PCP, I) and many of its derivatives have demonstrated many pharmacological effects. They interact with a number of neurotransmitter systems within the... (Review)
Review
Phencyclidine (PCP, I) and many of its derivatives have demonstrated many pharmacological effects. They interact with a number of neurotransmitter systems within the central nervous system. For example, Phencyclidine is a noncompetitive antagonist of the N-methyl-d-aspartate (NMDA) subtype of the glutamate receptor, and it causes the release and inhibits the reuptake of monoaminergic neurotransmitters, including dopamine, serotonin and norepinephrine. In this study, new thienyl (TCP, II), as well as benzothiophen (BTCP, III) derivatives (IV-VII) were synthesized. The acute and chronic pain activities of these drugs were studied using the tail immersion and formalin tests on mice and the results were compared with PCP, TCP and control groups at dosage of 10 mg/kg. The results indicated that the drug VII produced more analgesic effects on acute chemical pain in formalin test compared with other drugs. In addition, this analgesic effect was remarkably seen for drugs II, VI and VII in chronic pain in the mentioned test in comparison with other drugs. Also, the results showed that acute thermal pain could be diminished by drugs VI, II and I compared with other drugs in tail immersion test. It can be concluded that more analgesic effects of new BTCP analogues (VI and VII) may be concerned with antinociception activities of benzothiophene group and also with binding to cocaine site on the dopamine transporter receptor which seems to be more potent than PCP receptor in decreasing pain.
Topics: Analgesics; Animals; Male; Mice; Pain; Phencyclidine
PubMed: 24251803
DOI: 10.2174/1389557513666131119203551 -
Chemistry (Weinheim An Der Bergstrasse,... Feb 2021We report investigations of the use of cucurbit[8]uril (CB[8]) macrocycles as an antidote to counteract the in vivo biological effects of phencyclidine. We investigate...
We report investigations of the use of cucurbit[8]uril (CB[8]) macrocycles as an antidote to counteract the in vivo biological effects of phencyclidine. We investigate the binding of CB[8] and its derivative Me CB[8] toward ten drugs of abuse (3-9, 12-14) by a combination of H NMR spectroscopy and isothermal titration calorimetry in phosphate buffered water. We find that the cavity of CB[8] and Me CB[8] are able to encapsulate the 1-amino-1-aryl-cyclohexane ring system of phencyclidine (PCP) and ketamine as well as the morphinan skeleton of morphine and hydromorphone with K values ≤50 nm. In vitro cytotoxicity (MTS metabolic and adenylate kinase cell death assays in HEK293 and HEPG2 cells) and in vivo maximum tolerated dose studies (Swiss Webster mice) which were performed for Me CB[8] indicated good tolerability. The tightest host⋅guest pair (Me CB[8]⋅PCP; K =2 nm) was advanced to in vivo efficacy studies. The results of open field tests demonstrate that pretreatment of mice with Me CB[8] prevents subsequent hyperlocomotion induction by PCP and also that treatment of animals previously dosed with PCP with Me CB[8] significantly reduces the locomotion levels.
Topics: Animals; Bridged-Ring Compounds; HEK293 Cells; Hep G2 Cells; Humans; Imidazoles; Locomotion; Mice; Phencyclidine
PubMed: 33206421
DOI: 10.1002/chem.202004380 -
American Journal of Obstetrics and... May 1982Phencyclidine (PCP) is a dangerous and unpredictable drug which is widely abused among young people. Acute placental transfer of this drug was studied in pregnant...
Phencyclidine (PCP) is a dangerous and unpredictable drug which is widely abused among young people. Acute placental transfer of this drug was studied in pregnant rabbits and mice where it was shown to cross the placenta readily. Rabbit fetal levels of radioactivity reached their peak 2 hours after parenteral administration of PCP to the doe. In the mouse, where actual PCP levels were determined, there was a tenfold higher concentration of PCP in fetal tissue than in maternal blood. In lactating mice, the drug was found to cross rapidly into breast milk where it reached concentrations which were 10 times that of plasma. As PCP may be teratogenic and has been shown to be harmful to the infant during the postnatal period, those treating pregnant women should be aware to these possible routes of exposure for the developing infant and should counsel their patients accordingly.
Topics: Animals; Female; Half-Life; Lactation; Maternal-Fetal Exchange; Mice; Mice, Inbred ICR; Milk; Phencyclidine; Pregnancy; Rabbits
PubMed: 7081325
DOI: 10.1016/0002-9378(82)90643-3 -
Clinical Pharmacology and Therapeutics May 1982[3H]-Phencyclidine (PCP) hydrochloride was given in intravenous (0.1 or 1 mg) or oral (1 mg) doses to male subjects. After 1 mg IV, drug and metabolites were recovered...
[3H]-Phencyclidine (PCP) hydrochloride was given in intravenous (0.1 or 1 mg) or oral (1 mg) doses to male subjects. After 1 mg IV, drug and metabolites were recovered in urine (72.8 +/- 4.0% of dose), feces (4.7 +/- 0.9%), and perspiration. Fecal excretion was low (3.4 +/- 0.4%) after oral dosing and oral bioavailability was estimated at 72%. PCP comprised 16% of urinary radioactivity with 31% consisting of enzymatically hydrolyzable conjugates of hydroxylated metabolites. Both cis and trans isomers of 4-phenyl-4-(1-piperidinyl)cyclohexanol were found. Maximum average plasma PCP concentrations of 2.7 to 2.9 ng/ml were observed after oral and intravenous 1-mg doses. Blood/plasma ratios were approximately 1.0 and plasma binding was about 65%. Parent drug was found in saliva. Apparent terminal phase half-lifes averaged 21 +/- 3 hr (harmonic mean 17 hr, range 7 to 46 hr). The volume of distribution averaged 6.2 +/- 0.3 l/kg. Renal clearances were variable, but the average was 9% of the total clearance. Thus, PCP is cleared principally by metabolism.
Topics: Administration, Oral; Adult; Blood Proteins; Female; Humans; Hydrogen-Ion Concentration; Injections, Intravenous; Kinetics; Male; Phencyclidine; Protein Binding; Saliva
PubMed: 7075111
DOI: 10.1038/clpt.1982.87