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)

Water-deprived rats were given daily opportunities (2.0-hr sessions) to take water or a sweet solution (20% or 24% sugar-water). After stable intakes of each fluid were achieved, the effects of phencyclidine hydrochloride (PCP), delta-9-tetrahydrocannabinol (THC), ethanol (E), and morphine (M) on intakes were tested. PCP, THC, and M all enhanced intake of the sweet solution, while E produced varying effects across doses tested. With other rats, nearly the same procedure was used except that the test solution presented with water was 0.9% sodium chloride. Doses of PCP enhanced intake of the salty solution. These data, combined with the data from similar studies of the effects of opioids and benzodiazepines, indicate that a wide variety of agents that are self-administered also modify intake of ingesta.
Pharmacol Biochem Behav 1988 Dec
PMID:PCP, THC, ethanol, and morphine and consumption of palatable solutions. 285 70

Biochemical and electrophysiological studies have provided evidence that a complex comprising the N-methyl-D-aspartate (NMDA)-type excitatory amino acid (EAA) receptor and the phencyclidine (PCP) recognition site exists in mammalian brain. This complex, which has been compared to that established for the inhibitory amino acid, gamma-aminobutyric acid, and the benzodiazepine anxiolytic, diazepam, is sensitive to the effects of the divalent cation Mg2+, which has suggested the presence of a third, ion channel component. Using a radioreceptor assay for the PCP receptor, L-glutamate (L-Glu) produced a concentration-dependent increase in the binding of [3H]thienyl cyclohexylpiperazine ([3H]TCP) in well washed membranes from rat forebrain. The EAA produced a maximal increase in specific binding of 400%, with an EC50 value of 340 nM. The ability of L-Glu to enhance [3H]TCP binding was 10-fold more potent in the presence of 30 microM Mg2+, which inhibits NMDA-evoked responses in intact tissue preparations and produces a 50% increase in [3H]TCP binding on its own. Analysis of saturation curves indicated that the effect of both L-Glu and Mg2+ could be attributed to an increase in receptor affinity as well as increases in the proportion of a high affinity state of the PCP-binding site. Assessment of the effect of a number of EAAs on basal [3H]TCP binding (well washed membranes in the absence of either L-Glu or Mg2+) showed that the EAA recognition site involved in the effects of L-Glu was the NMDA subtype. Further studies examined a series of compounds thought to interact with either the NMDA or PCP components of the receptor complex under four binding conditions: basal, +Mg2+; +L-Glu; and +Mg2+/L-Glu. These results showed that dissociative anesthetics, such as dexoxadrol and PCP, as well as the novel anticonvulsant MK-801, selectively interact with the high affinity state of the PCP receptor. NMDA antagonists, such as CPP, were also found to inhibit binding to the high affinity state of the PCP receptor, although not as potently as the dissociative anesthetics. Interestingly, the NMDA antagonists did not inhibit any of the binding to the low affinity state of the receptor. The sigma ligands (+/-)-SKF 10,047 and haloperidol recognized two components of [3H]TCP binding only in the presence of L-Glu. The results of the present study are consistent with the finding that agonists of the NMDA receptor induce a high affinity state of the PCP receptor.
Mol Pharmacol 1987 Dec
PMID:Interaction of L-glutamate and magnesium with phencyclidine recognition sites in rat brain: evidence for multiple affinity states of the phencyclidine/N-methyl-D-aspartate receptor complex. 289 25

The effects of ethylketocyclazocine (EKC) on the stereotyped behaviors induced by intraperitoneal injection of phencyclidine (PCP) or N-allylnormetazocine (SKF 10,047) were examined. EKC markedly antagonized PCP-induced stereotyped behaviors such as sniffing, head-weaving, turning and backpedalling. On the other hand, EKC failed to antagonize SKF 10,047-induced stereotyped behaviors, which are PCP-like stereotyped behaviors, except sniffing and head-weaving at 0-15 min after the SKF 10,047 injection. PCP-induced turning and backpedalling were potentiated by pretreatment with SKF 10,047, while PCP-induced sniffing and head-weaving were not. EKC failed to affect the enhancing effect of SKF 10,047 on PCP-induced turning and backpedalling. These results suggest that part of the PCP- and SKF 10,047-induced stereotypy may be mediated by different neuronal mechanisms.
Pharmacol Biochem Behav 1987 Dec
PMID:Different effects of ethylketocyclazocine on phencyclidine- and N-allylnormetazocine-induced stereotyped behaviors in rats. 289 89

This study was designed to test whether phencyclidine (PCP)-induced turning behavior and locomotor stimulation result from the action of this drug on functionally different neuronal systems and different sites of the brain. PCP produced turning behavior towards the drug injection side with unilateral injection of PCP (50-100 micrograms) into the globus pallidus, but not the nucleus accumbens and the caudate nucleus. This turning behavior was strongly attenuated by a gamma-aminobutyric acid (GABA) antagonist, bicuculline, and by pimozide which reduces dopaminergic transmission in non-injection sites. Turning behavior induced by intraperitoneal injection of PCP (7.5 mg/kg) was enhanced by a GABA agonist, baclofen, and attenuated by GABA antagonists (bicuculline, picrotoxin). On the other hand, PCP produced significant locomotor stimulation, sniffing, rearing and forward locomotion with unilateral injection of 25-100 micrograms into the nucleus accumbens and the caudate nucleus. These behaviors were strongly antagonized by intraperitoneal injection of pimozide. The locomotor stimulation induced by intraperitoneal injection of PCP (5 mg/kg) was markedly enhanced by a small dose of methamphetamine and, by contrast, attenuated by reserpine, 6-hydroxydopamine, haloperidol, pimozide and a low dose of apomorphine which inhibits the release of dopamine by the stimulation of presynaptic receptors. These results suggest that PCP-induced turning behavior may be produced through stimulation of GABAergic transmission in the globus pallidus, although PCP-induced locomotor stimulation, sniffing, rearing and forward locomotion may be produced by increasing dopaminergic transmission in the nucleus accumbens and the caudate nucleus.
J Pharmacobiodyn 1986 Dec
PMID:Role of dopaminergic and GABAergic mechanisms in discrete brain areas in phencyclidine-induced locomotor stimulation and turning behavior. 303 92

Phencyclidine (PCP) abuse has diminished since PCP's intrusion into American culture in the late 1970s. One of its legacies is the assumption that it provokes violent behavior in humans with predictable regularity. This assumption is so accepted that ingestion of the drug both accidentally and knowingly prior to committing a crime has been used as a defense in criminal trials. We reviewed 81 clinical reports of toxicity in humans published chiefly in North American medical journals. We searched for descriptions of violent behavior in these reports and subjected them to the following questions: (1) Was the violent behavior corroborated or only self-reported? (2) Was the presence of PCP confirmed by analysis of bodily fluids or postmortem tissue? (3) Was the presence of other drugs excluded by similar analysis of bodily fluids? We had planned to examine the reports to see whether clinicians sought evidence of previous violent behavior, but such an inquiry was rarely conducted. Of the hundreds of patients described, only three satisfied these criteria. Further, some of the papers offered evidence that reports of violence were exaggerated. These findings plus the pre-1970 prospective evaluation of thousands of patients with PCP, in which violence was never reported, led us to conclude that clinical and forensic assumptions about PCP and violence are not warranted.
J Clin Psychopharmacol 1988 Dec
PMID:Phencyclidine and violence: clinical and legal issues. 306 80

The effects of prenatal administration of phencyclidine (PCP) on the learning and memory processes of rat offspring were investigated at doses below the level for producing malformations. The offspring prenatally treated with PCP (10 or 20 mg/kg) on days 7 to 17, as well as on days 7 to 21 of gestation, showed disruption of the acquisition of passive avoidance response and pole-climbing avoidance response at the ages of 4 and 7 weeks, respectively. The brain weight of the offspring prenatally treated with PCP was significantly decreased. These results suggest that prenatal PCP administration impairs learning and memory processes of passive and active avoidance tasks and that more attention should be given to the developmental toxicity of PCP.
J Pharmacobiodyn 1988 Dec
PMID:Effects of prenatal administration of phencyclidine on the learning and memory processes of rat offspring. 315 Dec 13

Five rhesus monkeys were trained to self-administer orally-delivered phencyclidine (PCP) and water under concurrent fixed-ratio (FR) 8 schedules. Liquid deliveries were contingent upon lip-contact responses on solenoid-operated drinking spouts, and food pellet delivery was contingent upon responses on a centrally-located lever. Food was available during three 1-hr periods each day under an FR 64 or FR 80 schedule. The liquids were available during three 6.5-hr periods after each food component. In the first experiment caffeine (4 or 8 mg) was added to each 6-g food pellet, and after responding stabilized, noncaffeinated pellets were substituted for the caffeinated pellets for eight days. There were no differences in food-, water- or PCP-maintained behavior due to caffeine concentration (4 vs. 8 mg/pellet) although the monkeys consumed twice as much caffeine at the higher concentration. Food-maintained responding was reliably reduced by 25-50 percent the first day of caffeine removal, and there was a recovery of responding characterized by intermittent cycles of low response rates over the next 7 days. Water and PCP intake were not systematically disrupted when caffeine access was terminated. In the second experiment the monkeys were tested with caffeinated (6 mg/pellet) and noncaffeinated pellets under conditions of PCP removal (water substitution) and reinstatement. Under both food conditions, when PCP access was terminated, pellet deliveries decreased by about 50 percent and gradually recovered over the 8-day water substitution phase. However, behavioral disruptions were more severe under conditions in which monkeys received caffeinated pellets, suggesting an interactive effect due to termination of PCP access and decreased caffeine intake. These results indicate that disruptions in operant baselines are sensitive indicators of the effects of discontinuing caffeine access; however, the severity and time course of behavioral disruptions due to caffeine removal are considerably less than after termination of PCP access.
Pharmacol Biochem Behav 1988 Dec
PMID:Behavioral dependence on caffeine and phencyclidine in rhesus monkeys: interactive effects. 325 84

In extensively washed preparations of rat cortical membranes, N-methyl-D-aspartate (NMDA) increases the specific binding of [3H]TCP by over 4-fold in a concentration dependent manner (EC50 = 3.1 microM). Glycine (1 microM) potentiates the maximal effect of NMDA by a factor of 1.7. The effect of glycine is concentration dependent (EC50 = 380 nM) and strychnine insensitive. These data are discussed with reference to the recently reported effects of glycine on the NMDA operated cation channel and the relationship between the PCP and NMDA receptors.
Neurosci Lett 1987 Dec 29
PMID:Glycine potentiates N-methyl-D-aspartate-induced [3H]TCP binding to rat cortical membranes. 332 17

The effects of phencyclidine (PCP; 0.5, 1,5, 10 mg/kg, i.v.) on local cerebral glucose utilization (LCGU) in the rat were studied with the 2-deoxy-D-[1-14C]glucose method. Significant findings were obtained in 41 of 87 brain regions of PCP-treated rats (25-270% of control). Rates of LCGU increased throughout the limbic system, except the habenula. Although LCGU increased in most sensory structures, it decreased in specific layers of the somatosensory and auditory cortices and the inferior colliculus. Evidence was seen for dissociation between LCGU responses of specific thalamic relay areas and their terminal fields in the cortex. Increases in LCGU occurred throughout the motor system, manifesting a striking pattern of columnar activity in the motor cortex. However, LCGU was reduced in the frontal cortical pole. Elevated LCGU was observed in the pontine nuclei and the nuclei and the nucleus solitarius. Effects of 5 mg/kg PCP diminished with time although 8 regions maintained a metabolic alteration at 180 min. PCP induced several behaviors, including stereotypies, which varied with the dose and time after drug administration. The results demonstrate a PCP-induced activation of various functional circuits in the brain, especially the limbic system, and may provide a physiological basis for PCP's psychotomimetic properties.
Brain Res 1987 Dec 01
PMID:Alterations in local cerebral glucose utilization induced by phencyclidine. 342 57

The behavioral effects of phencyclidine (PCP) and ketamine administered alone and in combination with naloxone, atropine, methyl atropine, chlorpromazine and d-amphetamine were studied in squirrel monkeys trained to press a response lever under a fixed-ratio 30 schedule maintained by the termination of a stimulus associated with electric shock presentation. Under non-drug conditions, a period of high-rate responding in the presence of the stimulus associated with shock presentation was followed by a period of no responding during a 40-s timeout scheduled between fixed-ratio components. Mean rates of responding during fixed-ratio components decreased monotonically as PCP dose increased from 0.1 to 0.56 mg/kg, and doses of 3.0 and 5.6 mg/kg ketamine produced decreases in mean response rate comparable to doses of 0.3 and 0.56 mg/kg PCP. The dose-effect functions revealed that ketamine was approximately one-tenth as potent as PCP. The present data also characterized the time-course effects of PCP and ketamine, with the former having effects that were slower in onset yet more persistent in time. None of the drugs studied in combination with PCP and ketamine provided evidence of a pharmacological antagonism of the behavioral effects of the latter two drugs. Rather, the data indicated an enhancement of behavioral effects when certain drug combinations were studied.
Eur J Pharmacol 1987 Dec 15
PMID:Behavioral effects of phencyclidine and ketamine alone and in combination with other drugs. 344 Apr 79


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