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)

Vigabatrin and (S)-4-allenylGABA (MDL 72483), two anticonvulsant GABA-T inhibitors, partially antagonize phencyclidine (PCP)-induced hyperactivity in mice at doses that do not affect spontaneous motor activity. The PCP antagonism is related to whole-brain GABA concentrations. The results indicate the potential use of GABA-T inhibitors in the therapy of PCP intoxications and perhaps also in the treatment of certain forms of endogenous psychoses.
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PMID:Antagonism of phencyclidine-induced hyperactivity in mice by elevated brain GABA concentrations. 158 40

The electrophysiological effects of phencyclidine (PCP) were measured intracellularly in guinea pig hippocampal CA1 neurons in vitro. At all doses tested (0.2 microM - 10 mM), PCP increased the width of action potentials (APs). Doses of 10 microM and higher were associated with decreased action potential amplitude. PCP decreased inhibitory postsynaptic potentials and excitatory postsynaptic potentials but did not alter responses to focally applied GABA. At the lowest dose (0.2 microM), PCP decreased the input resistance (Rin), while at all other doses Rin was increased. PCP decreased post-spike train afterhyperpolarizations at low and medium doses. PCP effects persisted in low calcium medium and also in medium containing 10(-6) M tetrodotoxin. It is concluded that in these central neurons, PCP primarily blocks potassium conductances at all doses and, at anesthetic doses, depresses sodium-dependent spikes.
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PMID:Phencyclidine actions measured intracellularly in hippocampal CA1 neurons. 207 27

The purpose of this experiment was to investigate the interactions of norepinephrine with PCP (phencyclidine) and sigma receptor agonists--modulated GABA (gamma aminobutyric acid) response in the cerebellum. Drugs were directly applied to a single cerebellar Purkinje neuron of urethane-anesthesitized rat through a multibarrel pipette. (+)PCMP [1-(-1-phenylcyclohexyl)-3-methyl piperidine], a PCP receptor agonist, and dexoxadrol, a sigma receptor agonist, significantly enhanced GABA induced inhibition. In norepinephrine-depleted animals, however, both (+)PCMP and dexoxadrol did not modulate GABA's effect. In conclusion, our findings indicated that the PCP/sigma-induced facilitation of GABA reactions were mediated through noradrenergic system in the cerebellum.
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PMID:Facilitation of GABA-induced depression with PCP and sigma receptor agonists was mediated through catecholaminergic pathways. 217 28

The effects of non-NMDA receptor agonists were tested on endogenous GABA and [3H]GABA release from highly purified striatal neurons differentiated in primary culture. Kainate (KA), glutamate (Glu) and quisqualate (QA) stimulated [3H]GABA release with EC50S = 85 +/- 20 (n = 6), 6.21 +/- 1.42 (n = 3) and 0.135 +/- 0.035 (n = 3) microM, respectively. KA was the most potent (in term of efficacy) agonist (maximal response at 10 mM: 935 +/- 51% (n = 6) increase over basal release) followed by Glu (at 100 microM: 404 +/- 34% (n = 5) increase) and QA (at 10 microM: 91 +/- 6% (n = 6) increase). Phencyclidine (PCP), which was without effect on QA- and KA-evoked GABA release, inhibited the Glu response by about 50%. QA totally inhibited KA (50 microM)-evoked GABA release with an IC50 = 0.39 +/- 0.11 (n = 4) in a competitive manner (Ki = 0.39 +/- 0.07 microM (n = 3]. Competitive inhibition of the KA response was also observed with the other agonists of the quisqualate receptor, Glu and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), suggesting that Glu, QA and AMPA act as partial agonists at the KA receptor. gamma-D-Glutamylaminomethylsulfonic acid (GAMS) also inhibited (IC50 = 2.1 mM) the KA response competitively. However the inhibition by GAMS and QA was not additive. The response to QA was rapidly inactivated (no response after 3 min stimulation) in contrast to the KA-evoked GABA release which remained maximal for at least 3 min. When neurons were first exposed to concanavalin A (con A), a lectin known to inhibit Glu receptor desensitisation on insect muscles, the QA response remained maximal for at least 6 min. Con A greatly enhanced the maximal responses to QA and AMPA and decreased their apparent affinities. The KA-evoked GABA release (but not the veratridine and NMDA effects) was also augmented (no change in the EC50 value) by con A. It is proposed that QA, AMPA and KA act at the same receptor-channel complex (termed G2 receptor) which is desensitised more rapidly when stimulated by QA or AMPA than when stimulated by KA.
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PMID:Complex interaction between quisqualate and kainate receptors as revealed by measurement of GABA release from striatal neurons in primary culture. 254 Oct 1

1. The effects caused by the dissociative anaesthetic drugs (PCP, KT), the sigmaopiates (SKF 10.047, cyclazocine), and the mixed excitatory amino acid antagonist CCP on the electrical activity of the red nucleus in rabbits were compared with PB. 2. Ketamine (10 mg/kg, i.v.) induced the appearance of a pentobarbital-like EEG synusoidal rhythm characterized by an increase in amplitude and a decrease in frequency of the basal electrical activity at the red nucleus level. 3. Both pentobarbital and ketamine induced rhythms were blocked by the GABA-antagonist pentylenetetrazol at the subconvulsant dose of 10 mg/kg, i.v. 4. Phencyclidine, SKF 10.047, cyclazocine, and the mixed excitatory amino acid antagonist CCP failed to affect the basal electrical activity of the red nucleus. 5. These data indicate an interaction of ketamine on the GABA neurotransmission at the level of cerebello-rubral pathways which the other PCP/sigma opiates did not present.
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PMID:Pentobarbital-like electroencephalographic rubral rhythm induced by ketamine in rabbits. 254 79

1. Convulsions were induced reproducibly by intracerebroventricular injection of N-methyl-D-aspartic acid (NMDA) to conscious mice. 2. Competitive (carboxypiperazine-propylphosphonic acid, CPP; 2-amino-7-phosphonoheptanoic acid, AP7) and non-competitive (MK801; phencyclidine, PCP; thienylcyclohexylpiperidine, TCP; dextrorphan; dextromethorphan) NMDA antagonists prevented NMDA-induced convulsions. 3. Benzodiazepine receptor agonists and partial agonists (triazolam, diazepam, clonazepam, Ro 16-6028), classical anticonvulsants (diphenylhydantoin, phenobarbitone, sodium valproate) and meprobamate were also found to prevent NMDA-induced convulsions. 4. Flumazenil (a benzodiazepine receptor antagonist) and the GABA agonists THIP and muscimol (up to subtoxic doses) were without effect. 5. Flumazenil reversed the anticonvulsant action of diazepam, but not that of MK801. 6. Results obtained in this model differ somewhat from those described in a seizure model with systemic administration of NMDA. An explanation for this discrepancy is offered. 7. This model is a simple test for assessing the in vivo activity of NMDA antagonists and also expands the battery of chemically-induced seizure models for characterizing anticonvulsants not acting at NMDA receptors.
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PMID:Convulsions induced by centrally administered NMDA in mice: effects of NMDA antagonists, benzodiazepines, minor tranquilizers and anticonvulsants. 257 61

The purpose of this experiment was to investigate the interaction of GABA (gamma aminobutyric acid) with PCP (phencyclidine) and sigma receptor agonists in the cerebellum. Drugs were applied directly to a single cerebellar Purkinje neuron of urethane-anesthetized rats, through a multibarrel pipette. The PCP receptor agonist, (+)PCMP [1-(-1-phenylcyclohexyl)-3-methyl piperidine], significantly enhanced GABA-induced inhibition. On the other hand, its stereoisomer, (-)PCMP, had no such modulatory effect. Dexoxadrol, a sigma receptor agonist, similar to (+)PCMP, potentiated GABA-induced depression. Its stereoisomer, levoxadrol, although inhibiting the spontaneous firings of Purkinje neurons, did not alter the effect of GABA. In conclusion, the findings indicate that the electrophysiological mechanisms of PCP-induced facilitation of GABA-induced reactions are similar to those triggered by sigma agonists in the cerebellum.
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PMID:Facilitation of gamma-aminobutyric acid-induced depression by (+)PCMP and dexoxadrol in the cerebellar Purkinje neurons of the rat. 274 47

An automated technique for the continuous analysis of different frequency bands of the electrocorticogram (ECoG) of the rat has been used to quantify the actions of phencyclidine (PCP) and various other stimulant drugs. It has been demonstrated that phencyclidine, etoxadrol and LY154045 produced similar changes in the individual frequency bands whereas amphetamine and apomorphine had different profiles of activity. The phencyclidine-like compounds exhibited extremely strong stimulation of the ECoG with very large increases recorded in high frequency (15-50 Hz) activity and reductions in all other frequency bands. Various compounds have been used in an attempt to antagonise the changes in the ECoG. Chlorpromazine caused a slight shift in the dose-response curves as did chlordiazepoxide when used with phencyclidine. The GABA agonists, THIP and muscimol, had no effect on the stimulation of the ECoG. In contrast another presumed GABA agonist, baclofen, proved to be the most effective agent for blocking the stimulation induced by phencyclidine. The role of the GABAB receptor in the action of phencyclidine is discussed.
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PMID:Quantitative electrocortical changes in the rat induced by phencyclidine and other stimulants. 286 May 91

The inhibition of [3H]TCP binding to rat cortical membranes by substances of the PCP/sigma-opiate type was compared with effects of the same compounds on N-methyl-D-aspartate (NMDA) responses in cultured mouse cortex neurons. A new technique of excitatory amino acid-induced [3H]GABA (gamma-amino-butyric acid) release in a continuous superfusion model was used for the purpose. A similar rank order of potencies was found for the substances whether as inhibitors of [3H]TCP binding (MK 801 greater than PCP greater than ketamine-cyclazocine) or as antagonists of NMDA (20 microM)-stimulated [3H]GABA release in the cultured neurons (phencyclidine = MK 801 greater than ketamine greater than cyclazocine).
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PMID:Phencyclidine analogues inhibit NMDA-stimulated [3H]GABA release from cultured cortex neurons. 331 51

The ability of intracisternal insulin-like growth factor II (IGF II) to inhibit gastric acid secretion was studied in rats. Centrally-administered IGF II dose-dependently inhibited acid secretion stimulated by pentagastrin. The effect was abolished by vagotomy. IGF II did not inhibit acid secretion stimulated by histamine or PCP-GABA.
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PMID:Central nervous system inhibition of pentagastrin-stimulated acid secretion by insulin-like growth factor II. 338 94


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