Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.16.2 (PCP)
3,761 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Six cases of PCP intoxication in young children age 5 years and younger seen at UCLA Medical Center recently and 10 other cases from the literature are described and their clinical findings summarized. PCP intoxication should be suspected in young children and infants presenting with rapid onset of lethargy or coma, strange behavior, staring spells, ataxia, and nystagmus. Other findings less frequent but still suspect are opisthotonos, hypertension, tachypnea or hyperpnea, miosis, hyperreflexia, hypertonia, and rigidity. Once suspected, the diagnosis is most easily made by finding PCP in the urine. Proper diagnosis of PCP intoxication is important to ensure that rapid, appropriate treatment is given, costly diagnostic workups are avoided, and family evaluations are instituted. One case strongly suggests that intoxication in infants may result from accidental inhalation when near individuals who are smoking PCP.
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PMID:PCP intoxication in young children and infants. 738 38

The influence of cholecystokinin (CCK), bilaterally injected into the rostral nucleus accumbens, on the EEG and behavioural effects induced by phencyclidine (PCP) has been studied in rats. CCK (10 ng) significantly inhibited PCP-induced EEG effects (increase of spectral power with respect to pre-drug tracing; increase of relative power distribution in the slowest frequency bands), and behavioural effects (circling and ataxia). The inhibitory effects of CCK were completely antagonized by 1 ng PD 135-158, a selective CCKB receptor antagonist, but not by lorglumide (1 microgram), a selective CCKA receptor antagonist. Since the effects induced by PCP in rodents have been proposed to be an experimental correlate of the psychotic symptoms it induces in humans, these results indicate that CCK may act as a neuroleptic. They also suggest that CCKB receptors located in the rostral nucleus accumbens may be involved in the neuroleptic-like activity of CCK.
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PMID:The stimulation of cholecystokinin receptors in the rostral nucleus accumbens significantly antagonizes the EEG and behavioural effects induced by phencyclidine in rats. 748 May 47

Phencyclidine (PCP), in a dose of 15 mg/kg, produced delayed cognitive dysfunction (at 24 h) in rats subjected to water maze tasks. At 24 h after PCP administration, ataxia, hyperlocomotion and stereotyped behavior were not induced. NE-100, N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]-enthylamine monohydrochloride, a selective and potent sigma receptor ligand, was administered orally 10 min after PCP administration or 15 min before the first trial (24 h after PCP administration). In both cases, NE-100 dose-dependently attenuated the delayed cognitive dysfunction induced by PCP. As these findings show that ingestion of PCP led to delayed cognitive dysfunction similar to the cognitive signs of psychosis seen in humans, NE-100 is being further studied for possible treatment of subjects with schizophrenia.
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PMID:Effect of NE-100, a novel sigma receptor ligand, on phencyclidine- induced delayed cognitive dysfunction in rats. 760 28

Behavioral and in vitro receptor binding methods were used to evaluate and compare the effects of FR115427 ((+)-l-methyl-1-phenyl-1,2,3,4-tetrahydroisoquinoline hydrochloride) with those of MK801, a non-competitive NMDA antagonist. FR115427 inhibited NMDA-induced convulsions in mice by intracerebroventrical(ICV) and systematic injection. FR115427 was found to be about ten times less potent than MK801. Furthermore, the inhibitory effect of FR115427 and MK801 on NMDA-induced convulsions was evaluated in time course studies in mice. MK801 exhibited a more sustained anticonvulsive activity than FR115427. In addition, PCP-like behaviors were examined in mice after ICV injection of these compounds. At the lowest dose FR115427 significantly increased locomotor activity, although the effect of this compound was about hundred times less potent than that of MK801. At higher dose a more complex pattern of behavior, e.g. head-movement and eventually ataxia was observed. In binding assays with rat brain membranes, FR115427 inhibited the binding of (3H)TCP (IC50 = 0.249 microM) and (3H)MK801 (IC50 = 0.312 microM) but did not inhibit the binding of (3H)CPP or (3H)glycine. These results suggest that FR115427 is a novel non-competitive NMDA antagonist that acts on a binding site located within the NMDA receptor associated ion channel.
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PMID:Behavioral studies on FR115427, a novel selective N-methyl-D-aspartate antagonist. 775 64

The N-methyl-D-aspartate (NMDA) subtype of excitatory amino acid receptors are involved in the electrical and behavioural generalization of epileptiform activity within the brain. In rats, both competitive and non-competitive NMDA antagonists induce three dose-dependent stages of EEG patterns: 1) increase in cortical desynchronization periods; 2) increase in amplitude of cortical high frequency (20-30 Hz), low voltage (30-50 microV) background activity; 3) appearance of cortical slow (2-3 Hz) wave-sharp wave complexes. These EEG changes are accompanied by stimulatory-depressive behavioural effects such as stereotypy (circling, head weaving) and ataxia. In the present study, the influence of the prototypic anticonvulsant diphenylhydantoin (DPH) has been tested on the EEG and behavioural effects induced by the non-competitive NMDA antagonists phencyclidine (PCP) and dizocilpine (MK-801) and by the competitive NMDA antagonist cis-4-phosphonomethyl-2-piperidine-carboxylic acid (CGS 19755). Even though DPH (up to 100 mg/kg IP) did not markedly affect basal cortical EEG activity, at doses of 10-100 mg/kg IP it potentiated all the EEG effects induced by the NMDA antagonists. These data support involvement of NMDA neurotransmission in the pharmacological effects of DPH.
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PMID:Diphenylhydantoin potentiates the EEG and behavioural effects induced by N-methyl-D-aspartate antagonists in rats. 786 61

SDZ EAA 494 (D-CPPene) was characterized as a competitive NMDA antagonist, having a pA2 value against NMDA depolarizations in frog spinal cord and rat neocortex of 6.7-6.8 and a pKi of 7.5 in a [3H]CGP39653 binding assay, with no action on other receptors or amine reuptake. The compound was orally active in rodent maximal electroshock models with an ED50 of around 16 mg/kg, was protective in rats even 24 hours after oral application and had an oral therapeutic index of around 8. Muscle relaxation, ataxia, flattened body posture and reduced acquisition of a passive avoidance task, suggesting potential effects on memory formation, occurred at supra-anticonvulsant doses in rodents, with PCP-like stimulatory effects produced only by high i.p. doses or constant i.v. infusions. This favourable profile is discussed in relation to the negative outcome of a recent trial of the compound in patients with intractable epilepsy. The conclusion is drawn that standard models for screening new anticonvulsants are inappropriate to seeking drugs active in patients with a protracted convulsive history. The anti-ischaemic action of SDZ EAA 494 encourages further testing in brain trauma, in which the anticonvulsant action of the compound may be an added benefit.
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PMID:The pharmacology of SDZ EAA 494, a competitive NMDA antagonist. 789 35

Intracerebroventricular injection of the D-forms of alanine (Ala; 2-200 micrograms/rat) and serine (Ser; 20-2000 micrograms/rat) caused a dose-dependent inhibition of the ability of 10 mg/kg of phencyclidine (PCP; given i.p.) to increase automatically quantitated locomotor counts and cumulated scores of locomotion, stereotypy and ataxia for 90 min after PCP administration. D-Ala and D-Ser were found to be more potent than the corresponding L-isomers in attenuating the PCP-induction of these behavioral abnormalities. Although L-, but not D-Ser, at moderate doses (400 micrograms/rat) produced a slight decrease in cumulative ataxia scores after a 10-mg/kg PCP administration, D-, but not L-Ser, reduced the behavioral scores at large doses (more than 1000 micrograms/rat). Similarly, bilateral i.c.v. infusion of D-Ala (140 micrograms/rat) reduced the increasing effects of a lower dose of PCP (5 mg/kg i.p.) on locomotion, stereotypy and ataxia scores, whereas the L-form of Ala (140 micrograms/rat) lacked the inhibitory influence. The stereo-selectivity of the antagonism by Ala and Ser of PCP-induced abnormal behavior parallels that of the potencies of these amino acids as agonists for the strychnine-insensitive glycine site linked to the N-methyl-D-aspartate type excitatory amino acid receptor. Furthermore, the decreasing effects of D-Ala (200 micrograms/rat i.c.v.) and D-Ser (2000 micrograms/rat i.c.v.) on PCP-induced hyperactivity were antagonized by i.c.v. application of 5,7-dichlorokynurenate and 7-chlorokynurenate which are selective antagonists of the glycine modulatory site.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Stereoselective antagonism by enantiomers of alanine and serine of phencyclidine-induced hyperactivity, stereotypy and ataxia in the rat. 801 48

Locomotor activity, ataxia, and stereotypy were assessed in the open field after administration of NMDA and AMPA antagonists acting by different mechanisms. The interaction with glutamatergic receptors was confirmed in the binding assay. (+)MK-801 and phencyclidine (PCP) produced similar changes in horizontal activity, i.e., a strong increase from the beginning of the test. Ketamine, and to a lesser extent, memantine, enhanced horizontal activity at the later observation periods only. Amantadine and NBQX produced a slight inhibition, while GYKI-52466, d-cycloserine, (+R)-HA-966, CGP-37849, and dextromethorphan were ineffective. Vertical activity (rearings) were inhibited by most agents except GYKI-52466 and gly-B partial agonists. At higher doses ataxia was seen after: MK-801, PCP, ketamine, memantine, amantadine, CGP-37849, dextromethorphan, and GYKI-52466. Hence, the inhibition of NMDA and AMPA receptors by agents acting at different recognition sites produces qualitatively different behavioral consequences.
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PMID:Glutamate antagonists have different effects on spontaneous locomotor activity in rats. 802 81

Phencyclidine (PCP)-induced psychosis is a useful animal model for studies on schizophrenia. N, N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)-phenyl]- ethylamine monohydrochloride (NE-100) had no effect on conditioned avoidance responses (CAR) in rats, whereas, the PCP-induced impairment of avoidance inhibition was attenuated by NE-100. The PCP-induced ataxia or decreased attention in rhesus monkeys was to some extent overcome by NE-100. In dogs, PCP-induced either head-weaving behavior or ataxia, effects which were blocked by NE-100. Administration of PCP led to an increase in beta-2 and a decrease in delta relative power (RP) activity in cortical background spectral electroencephalographics (ECoG) in dogs. While NE-100 in itself showed no significant change in beta-2 and delta RP, NE-100 did block the PCP-induced beta-2 increase and delta decrease. These findings indicate that NE-100 attenuates the effect of PCP in experimental animals. This drug is being considered as a therapeutic for the treatment of patients in the schizophrenia.
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PMID:NE-100, a novel sigma receptor ligand: effect on phencyclidine-induced behaviors in rats, dogs and monkeys. 804 Dec 25

Some non-competitive antagonists of N-methyl-D-aspartate (NMDA) were evaluated for potency to antagonize audiogenic seizures in genetically epilepsy-prone rats, following intraperitoneal administration. Phencyclidine (PCP), dizocilpine (MK-801), ketamine, ifenprodil and dextromethorphan, displayed anticonvulsant activity at doses similar to those which impaired performance in the rotarod equilibrium procedure. The noncompetitive NMDA receptor antagonists, at doses which slightly overlapped with the doses required for a full anticonvulsant protection against audiogenic seizures in genetically epilepsy-prone rats, induced profound untoward behavioural effects. This behavioural syndrome was characterized by marked ataxia, hyperactivity, stereotypes and wet dog shakes. In contrast, the effective anticonvulsant dose of 3-(2-carboxypiperazin-4-yl)propenyl-1-phosphonic acid (CPPene) was less than that required to impair rotarod performance and did not produce the PCP-like syndrome. A potential use in antiepileptic therapy, of CPPene or other new selective NMDA antagonists, with fewer neurotoxic effects but not for non-competitive antagonists such as MK-801, is suggested.
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PMID:Anticonvulsant properties of non-competitive antagonists of the N-methyl-D-aspartate receptor in genetically epilepsy-prone rats: comparison with CPPene. 809 34


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