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)

Intraperitoneal administration of phencyclidine (PCP, 2.5-20 mg/kg) produced a dose-related inhibition of the increase in serum PRL concentrations produced by alpha-methylparatyrosine (AMPT) or reserpine, but not morphine. Phencyclidine was more potent in antagonizing the PRL-releasing effect of reserpine than that of AMPT, suggesting a greater effect of PCP on the cytoplasmic than the storage dopamine (DA) pool. Phencyclidine had no effect on PRL release from rat pituitary glands in vitro. Intravenous administration of PCP (10 mg/kg) to anesthetized male rats produced a two-fold increase in pituitary stalk (DA) concentrations, suggesting that PCP inhibits rat serum PRL by increasing the release of DA from the tuberoinfundibular neurons, and possibly by blocking its reuptake as well.
 ...
PMID:Phencyclidine-induced inhibition of rat prolactin secretion: increased portal blood dopamine. 400 50

Phencyclidine (PCP) disposition kinetics has been examined in dogs as a function of dose and after i.v. and p.o. administration. Intravenous doses ranged from a tracer quantity of [3H]PCP to 5 mg/kg of unlabeled PCP. The elimination half-life of intact PCP was relatively short with harmonic mean values of 2.7, 5.4 and 3.9 hr for the tracer, 1- and 5-mg/kg doses, respectively. In contrast, measurement of total radioactivity gave a much longer half-life (35-52 hr) suggesting slower metabolite elimination. The drug has a large apparent volume of distribution (weighted mean of 20 liters/kg) and a systemic clearance (which is primarily metabolic) that approaches estimates of liver blood flow in the dog. Renal clearance of intact PCP represents a small fraction of total clearance. Percentage of the [3H]PCP dose recovered as total radioactivity was 49% in urine and 12% in feces. Several metabolites of PCP were determined in urine and they account for about 30% of the dose with the aminopentanoic acid derivative being present in the greatest amount. One of the hydroxylated metabolites is present in cis- and trans-forms, with the latter predominating. Three animals received an i.v. dose of [3H] PCP and a p.o. dose of unlabeled PCP at the same time to determine absolute bioavailability. Approximately 25% of the dose is absorbed intact. The p.o. (intrinsic) clearance of PCP is about four times greater than systemic clearance suggesting a blood flow-dependence in clearance and substantial first-pass hepatic metabolism.
 ...
PMID:Phencyclidine (PCP) disposition kinetics in dogs as a function of dose and route of administration. 403 85

Phencyclidine has a wide range of deleterious effects. Drug users may not even know that they have taken PCP since it is so easily disguised. Physicians should look for decreased reality testing, erythema, dry skin and other manifestations. The varied signs and symptoms of acute intoxication can be dealt with quickly and effectively. Management strategies include acidification of the urine and diuresis, as well as more specific antidotes, depending on the neurotransmitter system most affected.
 ...
PMID:Management of PCP intoxication. 407 64

Phencyclidine [(l-phenylcyclohexyl) piperidine] (PCP) is known to increase the basal efflux of striatal dopamine (DA) in vitro and to enhance haloperidol (HAL)-induced striatal DA metabolism in vivo. This study compared these activities of PCP to several representatives of the arylcyloalkylamine, benzomorphan and substituted dioxolane classes whose behavioral similarities to PCP have been well studied. The affinity of these drugs for the PCP/sigma opiate receptor also was estimated by determining the concentration of these drugs required to inhibit the specific binding of 10 nM [3H]PCP to rat cortical membranes by 50%. Of the arylcycloalkylamines tested on the basal efflux of [3H]DA, we found the rank-order effectiveness to be as follows: PCP greater than 1-[l-(napthyl)cyclohexyl]piperidine HCl (m-amino-PCP) greater than ketamine greater than or equal to 1-[l-(m-nitrophenyl)cyclohexyl]piperidine HCl (m-nitro-PCP) greater than N-ethyl-l-phencyclohexylamine (PCE). However, in vivo we found that PCP, m-amino-PCP and PCE significantly elevated HAL-induced DA metabolism, whereas ketamine and m-nitro-PCP were without effect. Although each of the benzomorphans tested [N-allylnormetazocine (NANM) and ethylketocyclazocine (EKC)] slightly enhanced the basal efflux of [3H]DA from striatal slices, concentrations of 10 to 30 microM were required to elicit the same magnitude of [3H]DA release caused by 3 microM PCP. Quantitatively similar responses were produced by the substituted dioxolanes tested (etoxadrol, dexoxadrol and levoxadrol). Neither (+)-NANM, (-)-NANM, (+/-)-NANM, etoxadrol nor dexoxadrol had any effect on HAL-induced DA metabolism. On the other hand, both levoxadrol and EKC significantly decreased the ratio of HVA/DA after HAL administration.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:A comparison between classes of drugs having phencyclidine-like behavioral properties on dopamine efflux in vitro and dopamine metabolism in vivo. 609 11

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.
 ...
PMID:Similar dopamine-releasing effects of phencyclidine and nonamphetamine stimulants in striatal slices. 612 3

The effect of phencyclidine (PCP) on the release and synthesis of [3H]-dopamine ( [3H]-DA) newly synthesized from [3,5-3H]-L-tyrosine was studied under both basal and potassium-stimulated conditions in slices from the rat striatum. Phencyclidine (3-100 microM) stimulated the release of [3H]-DA during superfusion with low level potassium (4.5 mM) buffer, but had no effect on the release of [3H]-DA elicited by superfusion with buffer containing 40 mM potassium. On the other hand, phencyclidine had no effect (except at 100 microm) on the spontaneous release of [3H]-H2O (formed as a result of the hydroxylation of [3,5-3H]-L-tyrosine), but inhibited the increase in formation of [3H]-H2O normally associated with potassium-induced depolarization. These data are discussed in relation to results obtained with phencyclidine on other in vitro and in vivo models of dopaminergic function.
 ...
PMID:Effects of phencyclidine on the release and synthesis of newly formed dopamine. 613 82

Phencyclidine (PCP) produces some neurochemical and behavioral effects in rats similar to those produced by the indirectly acting dopamine (DA) agonists amphetamine and amfonelic acid. In view of these findings, the effects of PCP, d-amphetamine and amfonelic acid on the release of DA in the rat striatum were examined by in vivo voltammetry. Drug effects on DA release were determined using newly developed electrodes selective for catecholamines. PCP (5 and 10 mg/kg IP) produced a dose-dependent decrease in the electrochemical signal that lasted for approximately 4 hr. In contrast, d-amphetamine (2.5 mg/kg, IP) and amfonelic acid (5.0 mg/kg, IP) both caused marked increases in electrochemical signals. The data provide evidence that PCP at the doses tested alters dopaminergic neurotransmission in a manner different from that of amphetamine and the non-amphetamine central nervous system stimulants by decreasing DA release from dopaminergic nerve terminals.
 ...
PMID:A comparison of CNS stimulants with phencyclidine on dopamine release using in vivo voltammetry. 615 66

Phencyclidine (PCP) at high doses causes both excitation and depression in the rat. The visual evoked potential (VEP) was measured in rats following PCP administration in doses ranging from 1 mg/kg to 56 mg/kg. Consistent lengthening of VEP latencies suggests that PCP has an unusual inhibitory effect on visual function in the presence of the excitatory signs of bilaterally synchronous cortical spiking. The epileptogenic properties of PCP are quite evident in rats.
 ...
PMID:Phencyclidine-induced alterations of rat electrophysiology. 626 54

[3H]Phencyclidine ([3H]PCP) binds specifically to an apparently single class of binding sites on slide-mounted sections of rat olfactory bulb (Kd = 46 nM; Bmax = 10.5 fmol per slice). Bound [3H]PCP can be displaced by nonradioactive PCP and a series of its analogs with relative potencies that correlate closely (P less than 0.001) with values determined in a rat discrimination test that utilized PCP as a cue. Although morphine, naloxone, and opiate peptides do not displace bound [3H]PCP, psychotomimetic benzomorphans, classed as "sigma opiates," are quite potent displacers in vitro and have PCP-like behavioral properties in vivo. These results suggest that phencyclidine and the sigma opiates act at the same sites. [3H]PCP binding sites were visualized by using tritium-sensitive LKB film analyzed by computerized densitometry and color coding. The [3H]PCP binds most densely to cortical areas, diffusely in neocortex, and somewhat heterogeneously in the laminae of the hippocampal formation and dentate gyrus. Most of the brainstem and spinal cord show low specific [3H]PCP binding, with gray matter generally showing more binding than white.
 ...
PMID:Phencyclidine (angel dust)/sigma "opiate" receptor: visualization by tritium-sensitive film. 627 22

Phencyclidine (PCP) and its 3-hydroxy derivative (PCP-3-OH) caused a dose-dependent, naloxone reversible inhibition of the response of the guinea pig ileum to electrical stimulation. Unlike PCP, PCP-3-OH exerted an opioid antagonistic effect in the mouse vas deferens bioassay. Whereas both compounds displayed a high affinity in displacing [3H]SKF-10047 binding to rat brain membranes, PCP-3-OH displayed a high affinity to [3H]morphine receptors also. The mediation of alpha- and mu-receptors in the opioid effects of these drugs is discussed.
 ...
PMID:On the opioid nature of phencyclidine and its 3-hydroxy derivative. 627 87


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>