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

---

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

A behavioural study on the effects of D1 and D2 dopamine receptor antagonists (SCH 23390 and sulpiride respectively) and of an A1 adenosine receptor agonist (N6-L-phenylisopropyladenosine, L-PIA) against phencyclidine (PCP)-induced effects was assessed in adult male rabbits. SCH 23390 (0.003-0.01 mg/kg i.v.) and sulpiride (12.5 mg/kg i.v.) were able to significantly prevent PCP-induced stereotypy. Ataxia was reduced by SCH 23390 (0.003 mg/kg i.v.), while it was potentiated by sulpiride (12.5 mg/kg i.v.). Given alone at 12.5 mg/kg, sulpiride induced some EEG and behavioural effects in rabbits, while SCH 23390 (0.003 and 0.01 mg/kg) did not. L-PIA prevented both PCP-induced stereotypy and ataxia at the dose (0.1 mg/kg i.v.) devoid of behavioural or EEG effects by itself. Our results suggest that D1 dopamine receptors might play a more important role than D2 receptors in the expression of PCP-induced behaviour. They also propose that A1 adenosine receptors might be involved (e.g. via an influence on the dopamine release) in the behavioural effects of PCP.
...
PMID:Evidence of the involvement of D1 dopamine receptors in PCP-induced stereotypy and ataxia in rabbits. 218 22

Thirty-seven arylcyclohexylamines including phencyclidine (PCP) and derivatives, N[1-(2-thienyl)cyclohexyl]piperidine (TCP) and derivatives and N-[1-(2-benzo(b)thiophenyl)cyclohexyl]piperidine (BTCP) were assessed for their ability to inhibit [3H]PCP binding and [3H]dopamine ([3H]DA) synaptosomal uptake. Their pharmacological property (ataxia) was measured by means of the rotarod test. A very good correlation was observed between the inhibition of [3H]PCP binding and the [3H]DA uptake only for arylcyclohexylamines bearing an unmodified phenyl group. Conversely the comparison between the inhibition of [3H]PCP binding and the activity in the rotarod test shows a good correlation with arylcyclohexylamines having any aromatic group (phenyl, substituted phenyl and thienyl rings). This study outlined a new compound (BTCP) without ataxic effect, which is one of the more potent inhibitors of the [3H]DA uptake (IC50 = 8 nM) and which seems very specific since it has a low affinity for [3H]PCP receptors (IC50 = 6 microM). These data show that the aromatic group of the compounds leads to molecules that bind differently to the PCP receptor and to the DA uptake complex. They also suggest that the behavioral properties of arylcyclohexylamines revealed by the rotarod test occur essentially as a result of an interaction with the sites labeled with [3H]PCP and that TCP is more selective than PCP itself in this recognition.
...
PMID:Role of the aromatic group in the inhibition of phencyclidine binding and dopamine uptake by PCP analogs. 254 5

The selective non-competitive NMDA receptor antagonist, MK-801, potently blocked convulsions induced in the mouse by N-methyl-DL-aspartic acid (NMDLA) with an i.v. ED50 dose of 0.2 mg/kg. Similar doses of MK-801 were also effective in blocking seizures induced by pentylenetetrazol (PTZ), electroshock and by sound in audiogenic seizure-prone animals. Other less selective non-competitive NMDA receptor antagonists including phencyclidine (PCP), thienylcyclohexylpiperidine (TCP), (+)-N-allylnormetazocine [+)-NANM, (+)-SKF 10,047) and ketamine also blocked NMDLA-induced seizures with a rank order of potency of MK-801 greater than PCP greater than TCP = (+)-NANM greater than ketamine. The competitive NMDA receptor antagonist, 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) blocked NMDLA-induced seizures with an ED50 of 4.5 mg/kg, 22- and 560-fold more potently than the competitive antagonists, 2-DL-amino-7-phosphonoheptanoic acid (2-APH) and 2-DL-amino-5-phosphonovaleric acid (2-APV), respectively. MK-801 was the most potent of the non-competitive antagonists to induce a motor syndrome including head weaving, body rolling, increased locomotion and ataxia, characteristic of the behavioural response to PCP in the mouse. The syndrome was also present following injection of the competitive NMDA receptor antagonists, although they were generally less potent (probably a reflection of poor brain penetration) and less efficacious than the non-competitive antagonists. For all compounds except CPP, the anticonvulsant ED50 dose was close to the minimum effective dose to induce motor stimulation: CPP was 5- to 10-fold more potent as an anticonvulsant.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:The behavioural effects of MK-801: a comparison with antagonists acting non-competitively and competitively at the NMDA receptor. 255 Feb 53

The behavioral and biochemical effects of the noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801 [+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate) were compared with those of phencyclidine (PCP). In the dose range used in this study, MK-801 (0.125-0.5 mg/kg i.p.) produced ataxia and other behavioral responses which were similar to PCP (5-10 mg/kg i.p.). However, turning and backpedalling induced by MK-801 were not dose-dependent and less intense at the dose producing approximately the same level of ataxia as PCP. Neurochemically, MK-801 (0.5 mg/kg i.p.) increased dopamine turnover in the cortex and striatum, but had no effect on 5-HT systems. It was also 3.4 times less potent in inhibiting 5-HT uptake than PCP. These results suggest that the behavioral responses induced by MK-801 involve primarily the PCP receptor and the dopamine system, and that the differences from PCP reflect a reduced effect on the 5-HT neuronal system.
...
PMID:Comparison of the behavioral and biochemical effects of the NMDA receptor antagonists, MK-801 and phencyclidine. 255 33

The role of metabolism in the in vivo actions of phencyclidine (PCP) was examined by comparing deuterium-substituted drug with drug of normal isotopic abundance. PCP elicits two responses that differ in their time course, ataxia, which is observable immediately after dosage, and hypothermia, which peaks approximately 90 to 120 min after drug administration. The role of metabolism in these responses was determined by comparing bioavailabilities of deuterium enriched (d10) and normal (d0) PCP with the two responses. Plasma concentration was determined after the i.v. and i.p. administration of d10 and d0 drug and the bioavailability of the d10 was found to be 1.3 to 1.5 times the d0. The clearance of the d10 was also smaller than the d0. The d10, which is pharmacologically equivalent in vitro, is metabolized more slowly than the d0 in vitro. The pharmacokinetic and pharmacodynamic bioavailabilities exhibited comparable isotope effects, indicating that both responses are due to the actions of the parent drug.
...
PMID:Pharmacokinetic and pharmacodynamic evaluation of phencyclidine and its decadeutero variant. 274 98

Either phencyclidine hydrochloride (PCP) (5, 10, or 20 mg/kg) or saline was administered by subcutaneous injection to gravid CF-1 mice during either Mid (E6-15) or Late (E12-18) gestation. A nontreated control group (UTC) was left undisturbed during pregnancy. All treated and control litters were fostered at birth to untreated dams. Although postnatal challenge of PCP increased motor activity and ataxia in a dose-related manner, prenatal PCP had no effect on postnatal motor activity, ataxia or 3H-PCP binding. However, treatment period did have a significant effect on ataxia and 3H-PCP binding. In response to challenge doses of 5.0 and 7.5 mg/kg PCP, ataxia scores of the Late gestation offspring were significantly greater than the UTC offspring which in turn were significantly greater than the ataxia scores of the Mid gestation group. The results are discussed in relation to other animal and clinical reports of prenatal PCP exposure.
...
PMID:Effects of prenatal phencyclidine on 3H-PCP binding and PCP-induced motor activity and ataxia. 279 92

The purpose of this study was to examine the binding and behavioral effects mediated by PCP and sigma receptors in the rat. From the radioreceptor assays, it was possible to characterize two binding sites that interact with PCP and sigma ligands. The two sites, a PCP and sigma receptor, could be differentiated based on drug selectivity and potency. In the behavioral assays, MK-801, which bound preferentially to the PCP receptor, and 1,3-di-0-tolylguanidine, which bound preferentially to the sigma receptor, induced sniffing, rearing, circling, backpedaling, and weaving behavior. These results indicate that there are distinct PCP and sigma receptors that are both involved in mediating stereotyped behavior and ataxia in the rat.
...
PMID:Biochemical and behavioral effects of sigma and PCP ligands. 285 Jun 29

Pigeons were trained to discriminate either a fixed dose of PCP (1 mg/kg; n = 3) or a progressively decreasing dose (1-0.56-0.32 mg/kg; n = 4) from saline. Lowering of the training dose shifted the dose-effect curve for PCP's discriminative stimulus effects about 5-fold to the left, in a parallel manner, but did not decrease the accuracy of the discrimination performance and did not significantly increase the extent to which pentobarbital and chlordiazepoxide produced PCP-appropriate responding. Dose-effect curves based on binary generalization data were evaluated statistically with new methods that may be more appropriate than those used previously. Metaphit, a proposed PCP-receptor acylator, and 2-amino-5-phosphonovalerate (AP5), an N-methyl-D-aspartate (NMDA) antagonist, produced complete PCP-appropriate responding in the high training dose group only at doses that suppressed the rate of responding and that produced ataxia. However, 4-fold lower doses of metaphit and AP5, which did not produce directly observable behavioral effects, were found to substitute completely for PCP in the low training dose group. These data support the notion that PCP, metaphit, and AP5 have a common discriminative effect in pigeons.
...
PMID:Phencyclidine (PCP)-like discriminative stimulus effects of metaphit and of 2-amino-5-phosphonovalerate in pigeons: generality across different training doses of PCP. 289 14

Rats were used for comparing the behavioral response profiles of phencyclidine (PCP) and d,1-N-allylnormetazocine (NANM), two drugs that are proposed to exert their effects through the "PCP/sigma" receptor. Phencyclidine (1.0-5.0 mg/kg) and NANM (2.5-10.0 mg/kg) induced dose-related increases in locomotion, sniffing, repetitive head movements, non-object directed mouth movements, and ataxia. Both drugs also increased food and water consumption during the latter portion of the drug response. Ingestive behaviors induced by PCP (2.5 mg/kg), as with eating and drinking stimulated by the mu-opiate morphine (2.0 mg/kg), were blocked by a relatively low dose of the opiate antagonist naloxone (0.5 mg/kg). Multiple injections of PCP (2.5 mg/kg for 4 days) or NANM (10.0 mg/kg for 4 days) augmented several measures of behavioral activation, including horizontal locomotion, rearing, and nonfocused sniffing, but did not significantly change stereotyped behaviors or ataxia. Reciprocal cross-sensitization of locomotor activation is indicated by the finding that the response to a challenge injection of PCP (2.5 mg/kg) or to NANM (10.0 mg/kg) after 4 days of treatment with the other drug closely resembled the enhanced locomotor response observed after the chronic treatment. Phencyclidine and NANM thus appear to exert many of their effects on unconditioned behavior through common mechanisms, including interaction with sigma receptors. In addition, these findings are consistent with previous suggestions that a mu-opiate receptor system may modulate some effects of PCP.
...
PMID:Evidence for multiple opiate receptor involvement in different phencyclidine-induced unconditioned behaviors in rats. 300 79

Metaphit, a derivative of phencyclidine (PCP), binds irreversibly to PCP sites and appears to act as an antagonist of PCP under some conditions and as a PCP-like agonist under other conditions. To describe further these conditions, the authors investigated the behavioral effects of metaphit by using different routes of administration, behavioral procedures and species. In pigeons, metaphit induced PCP-like catalepsy after i.c.v. administration and, after i.m. administration, produced PCP-like discriminative stimulus effects and stereotyped operant responding. In rhesus monkeys, metaphit produced ataxia and convulsions but did not induce catalepsy, anesthesia or PCP-like discriminative stimulus effects. None of the effects of PCP-type drugs [i.e., PCP, ketamine or (+/-)-SKF 10,047] in pigeons or rhesus monkeys was antagonized by metaphit. Metaphit potentiated the discriminative stimulus effects of PCP and of SKF 10,047 in pigeons. These results suggest that metaphit acts not as an antagonist of PCP but as a PCP-like agonist under these conditions. Metaphit's potentiation of behavioral effects of PCP may be related to the presumed ability of metaphit to acylate PCP receptors. The extent to which metaphit produces PCP-like behavioral effects in part may be species dependent.
...
PMID:Metaphit, a proposed phencyclidine receptor acylator: phencyclidine-like behavioral effects and evidence of absence of antagonist activity in pigeons and in rhesus monkeys. 300 81


<< Previous 1 2 3 4 5 6 7 8 9 Next >>

---