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)

The effects of phencyclidine (PCP) on the dynamics of brain histamine (HA) were examined in the mouse brain. PCP (2-10 mg/kg i.p.) dose-dependently elevated the level of tele-methylhistamine (t-MH), a predominant metabolite of brain HA, without altering the HA level. PCP also enhanced the accumulation of t-MH after administration of pargyline hydrochloride (80 mg/kg i.p.). PCP at 5 mg/kg facilitated the HA depletion produced by (S)-alpha-fluoromethylhistidine markedly (50 mg/kg i.v.), a specific inhibitor of histidine decarboxylase. Metoprine (10 mg/kg i.p.), an inhibitor of HA-N-methyltransferase, decreased the t-MH level and increased the HA level. In the metoprine-treated mice, PCP at 10 mg/kg had no significant effect on the t-MH level, whereas it significantly increased the HA level. The increase in the t-MH level after administration of PCP (5 mg/kg) was observed in various brain regions except the pons-medulla oblongata. These results suggest that, in mice, PCP increases the brain HA turn-over possibly by facilitating the release of HA.
J Pharmacol Exp Ther 1985 Dec
PMID:Phencyclidine and the dynamics of mouse brain histamine. 407 33

Rats trained to discriminate intraperitoneally injected phencyclidine (PCP) from saline in a two-lever operant procedure distributed most of their responses on the phencyclidine lever after administration of 150 or 300 micrograms of phencyclidine into a lateral ventricle. This demonstrated that the discriminative stimulus properties of phencyclidine were centrally mediated. On the other hand, the potency of phencyclidine was increased by no more than about 7-fold from intraperitoneal to intraventricular administration. This suggests that either periventricular sites are not involved in mediating the discriminative stimulus properties of phencyclidine or that absorption of phencyclidine to relevant sites in the brain is not markedly enhanced by intraventricular administration.
Neuropharmacology 1985 Dec
PMID:A comparison of the discriminative stimulus properties of phencyclidine, given intraperitoneally or intraventricularly in rats. 409 54

The results of experiments are described in which attempts have been made to use the multi-site ligand (d,l)3H-SKF10047 to define a binding site that may be the opioid sigma site. This was attempted by using highly selective blocking agents to eliminate binding at the other opioid sites. The remaining bound 3H-SKF10047, approximately 20% of total specific bound, was then characterized using competitive binding studies with different types of opioids. Under these conditions, a binding site was identified which is highly selective for the benzmorphans and certain morphinans known to cause dysphoria. The kappa selective agent (l)U-50488 did not demonstrate high activity for this site and neither did several mu opioids, PCP or the (d) enantiomers of two opioid benzmorphans. The carefully defined site may be the putative opioid sigma receptor.
Neuropeptides 1984 Dec
PMID:3H-SKF10047 receptor binding studies. Attempts to define the opioid sigma receptor. 609 85

Phencyclidine (PCP) elicits some behavioral and biochemical effects in rodents which resemble the effects of other central nervous system stimulants. Because an indirect dopaminergic agonist role has been proposed for PCP, we have compared the dopamine (DA)-releasing properties of PCP, amphetamine and certain nonamphetamine stimulants (methylphenidate, nomifensine, amfonelic acid). Striatal slices from male albino Sprague-Dawley rats were incubated with [3H]DA (10 nM) and then superfused in microperfusion chambers with a modified Tyrode's buffer (pH 7.4). Drug effects on [3H]DA release during depolarizing (40 mM KCl) and nondepolarizing (basal) conditions were determined by comparison with drug-free DA release rates in each preparation. PCP (3-100 microM) and all central nervous system stimulants tested produced a concentration-dependent increase of basal [3H]DA release (potency order: amfonelic acid, amphetamine greater than nomifensine, methylphenidate greater than PCP). At higher concentrations, PCP and the nonamphetamine stimulants also enhanced stimulated [3H]DA release. The effect of PCP on basal release was unchanged by the removal of extracellular calcium, addition of tetrodotoxin (1 microM) or pretreatment of rats with reserpine. Nomifensine (1 microM) enhanced the DA releasing actions of PCP and other nonamphetamine stimulants, but antagonized the DA releasing action of amphetamine. PCP, at concentrations which did not affect basal DA release (less than 1 microM), also antagonized the action of amphetamine. From these results, it appears that PCP enhances DA release in a manner similar to the nonamphetamine class of central nervous system stimulants.
J Pharmacol Exp Ther 1982 Dec
PMID:Similar dopamine-releasing effects of phencyclidine and nonamphetamine stimulants in striatal slices. 612 3

To evaluate [3H]phencyclidine ([3H]PCP)as a probe for the ionic channel of the nicotinic receptor, the characteristics of its binding to electric organ membranes od Torpedo ocellata and its effects on frog sartorius muscle were studied. Similar to PCP, [3H]PCP depressed the peak amplitude of endplate current, caused nonlinearity in the voltage-current relationship at negative potentials, accelerated the decay time of the end-plate current, and shortened the channel lifetime. Thus, [3H]PCP interacted with the ionic channel of the nicotinic receptor, although there were a few differences between its effect and that of PCP. Binding of [3H]PCP to Torpedo membranes was to sites on the ionic channel of acetylcholine (AcCho) receptor because it was saturable, dependent upon protein concentration, and inhibited by drugs that interact with the ionic channel, and the initial rate of binding was potentiated by receptor agonists. Equilibrium binding of [3H]PCP to Torpedo membranes was with two affinities, but in the presence of AcCho, [3H]PCP binding was with a single affinity. The affinities of channel drugs obtained by inhibition of binding of [3H]PCP and [3H[perhydrohistrionicotoxin to Torpedo membranes were different, with correlation coefficients of 0.52 and 0.82 in the absence and presence of a receptor agonist, respectively; this suggests differences in their binding sites on the ionic channel of the AcCho receptor.
Proc Natl Acad Sci U S A 1980 Dec
PMID:[3H]Phencyclidine: a probe for the ionic channel of the nicotinic receptor. 626 Dec 60

The action of phencyclidine [1-(1-phenylcyclohexyl)piperidine; PCP] and its behaviorally active analog (m-amino-PCP) and of two behaviorally inactive analogs [m-nitro-PCP and 1-piperidinocyclohexanecarbonitrile (PCC)] were examined in this study. In a test of spatial alternation performance in rats, PCP and m-amino-PCP were much more potent behavior modifiers than were PCC and m-nitro-PCP. We studied the effects of the drugs on the ionic channels of the electrically excitable membrane and of the nicotinic acetylcholine (AcCho) receptors at the neuromuscular junction of frog skeletal muscle. All four compounds blocked the indirectly elicited muscle twitch and depressed the amplitude and rate of rise of directly elicited muscle action potentials. They also caused a voltage- and concentration-dependent decrease in the peak amplitude of the endplate current but did not react with the nicotinic AcCho receptor. These observations indicate that the four compounds have comparable blocking effects on the ionic channels associated with the nicotinic AcCho receptor. In contrast, the behaviorally active agents could be distinguished from behaviorally inactive ones by their effects on K+ conductance. PCP and m-amino-PCP blocked delayed rectification in frog sartorius muscles, prolonged the muscle action potential more than 2-fold, and markedly potentiated the directly elicited muscle twitch. The behaviorally active compound also blocked depolarization-induced 86Rb+ efflux from rat brain synaptosomes (presumably a measure of K+ conductance) and increased quantal content at the frog neuromuscular junction. In these actions, m-nitro-PCP was much less effective, and PCC was relatively ineffective. Because PCP and m-amino-PCP are much more potent behavior modifiers than PCC and m-nitro-PCP, we suggest that the behavioral effects of PCP and m-amino-PCP, may be due to a block of K+ conductance and enhancement of transmitter release at central neurons.
Proc Natl Acad Sci U S A 1981 Dec
PMID:The behavioral effects of phencyclidines may be due to their blockade of potassium channels. 627 89

The immune response of lymphocytes to subcutaneously administered pneumococcal vaccine was studied in five patients without spleens and in five healthy subjects. Seven days after immunisation circulating B cells synthesising IgG antipneumococcal capsular polysaccharides (anti-PCP) appeared in both groups. Twenty one days after vaccination this B cell population had disappeared and a B cell subset which secreted IgM and IgG anti-PCP in the presence of pokeweed mitogen was detected in the normal but not in the splenectomised subjects. In the splenectomised group polyclonal IgM synthesis induced by pokeweed mitogen was defective. It was concluded that the early events of the immune response to PCP may be mediated by lymph nodes but that, later, the spleen acquires a central role in producing lymphocyte subsets capable of synthesising specific antibodies and that this might explain the increased sensitivity of splenectomised subjects to pneumococcal infection.
Br Med J (Clin Res Ed) 1983 Dec 17
PMID:Role of spleen in immune response to polyvalent pneumococcal vaccine. 642 35

The effects of perinatal exposure to phencyclidine (PCP) on the reflex development of the offspring of mothers given PCP during gestation and/or lactation were determined. ICR Swiss mice received daily injections of either PCP (5, 10, 20 mg/kg, PO) or saline during gestation and/or lactation. Thus, four groups of animals were studied; those exposed only prenatally, postnatally, both pre- and postnatally, or control. After birth, these offspring were observed daily until weaning for the appearance of certain reflexes, using a modification of the Fox battery. There was a delay in the disappearance of the cross extensor reflex and delayed appearance of reflexes, such as walking, crawling, vibrissal placement and vibrissal stroking in the offspring of PCP-treated mothers. Treated animals also showed slower righting times than control animals. Growth rate was decreased in PCP-exposed animals beginning at 3 days of age and continuing through 15 days of age. These results indicate that PCP exposure during gestation or nursing adversely affects the development of behavioral reflexes in mice and suggest that regular observation of reflex ontogeny in neonates may be a sensitive indicator of behavioral teratology.
Teratology 1983 Dec
PMID:Phencyclidine exposure and the developing mouse: behavioral teratological implications. 666 32

Phencyclidine (PCP) and several behaviorally active or inactive structural analogs were administered i.v. to urethane-anesthetized rats in order to determine their effects on CA1 pyramidal cell discharges elicited by contralateral CA3 (cCA3) stimulation. PCP and the behaviorally active m-amino derivative (m-NH2 PCP) depressed, in a dose-dependent manner, the amplitude of the population spike evoked in CA1 by a cCA3 stimulation (ED 50s: 0.9 mg/kg for PCP, 0.5 mg/kg for m-NH2 PCP). However, the behaviorally inactive derivatives m-nitro (m-NO2 PCP) and PCP methyliodide (PCP CH3I) were ineffective up to 10 mg/kg. PCP (0.1-0.3 mg/kg i.v.) also decreased the duration of inhibition of CA1 discharges in a paired-stimulus paradigm; this was in contrast to the effects of thiopental and diazepam. In midcollicular-transected, urethane-anesthetized rats, the inhibitory effect of PCP on cCA3-CA1 transmission was not observed but the drug was still as effective as in intact rats in the paired-stimulus paradigm. In animals subjected to 6-hydroxydopamine lesions of the hippocampal noradrenergic innervation (average 85%) decrease in NE content), the potency of PCP in inhibiting cCA3-CA1 transmission was the same as in a group of sham-operated controls. These results suggest the following conclusions: (i) PCP exerts at least 2 separate types of effects in CA1, both of which result from a central action of the drug; (ii) PCP decreases the monosynaptic excitation of CA1 pyramidal cells and this action requires the integrity of brainstem afferents; (iii) PCP may decrease recurrent inhibition or afterhyperpolarization in CA1 via a mechanism which is independent of these connections and, therefore, could result from a direct action of the drug at the level of the hippocampus; (iv) finally, no evidence was found to suggest that the noradrenergic innervation of the hippocampus is critically involved in the action of PCP on CA1 discharges.
Brain Res 1982 Dec 09
PMID:Effect of phencyclidines on hippocampal pyramidal cells. 681 48

Extent and determinants of use of alcohol, marijuana, inhalants, and PCP were explored in a group of 339 Mexican American youths from the East Los Angeles Housing projects. Results from this study were compared to those from a similar survey carried out in the same area 2 years ago. Use of inhalants has declined markedly compared with prevalence reported in the previous report. However, use of alcohol and marijuana have increased across all age and sex cohorts. Prevalence of PCP use, explored for the first time in this report, was shown to be extremely high. Use of all drugs was generally predicted by age, sex, and number of peers reporting use. Self-concept factors, especially one's self-evaluation with respect to others, were also significant predictors to use of marijuana, inhalants, and PCP. However, alcohol use was not related to any self-concept factors. Language (Spanish-English) used both in the home and with peers was related to use of all substances studied. Limitations in the generalization of this study as a result of sampling problems are discussed.
Am J Community Psychol 1980 Dec
PMID:Correlates and changes over time in drug and alcohol use within a barrio population. 697 Oct 53


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