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)

The peripheral administration of the psychotomimetic drug phencyclidine (1-(phenylcyclohexyl) piperidine hydrochloride) (PCP) induces a dose-related ipsilateral rotation in unilateral substantia nigra electrolytically-lesioned rats. The intensity of this rotation can be modulated by administration of various dopaminergic and cholinergic agents. Injection of alpha-methylparatyrosine methylester (125 mg/kg) or haloperidol (1 mg/kg) inhibited the ipsilateral circling behavior. Pimozide (1 mg/kg) also inhibitied the rotation, but to a lesser extent. The injection of the anticholinergic agent trihexyphenidyl (5 mg/kg) potentiated, and the cholinomimetic drug arecoline (5 mg/kg), depressed the rotation induced by PCP (7.5 mg/kg), It is probable that PCP possesses significant dopaminergic and anticholinergic properties. The capacity of PCP to induce rotation in this model may be related to its effects on dopaminergic and cholingergic neurons in the rat striatum. Thus, PCP may induce rotational behavior by potentiating dopaminergic transmission, by blocking cholinergic activity, or both; both of these effects have been demonstrated to be important in the generation of circling behavior in rats with nigrostriatal lesions.
Pharmacol Biochem Behav 1976 Dec
PMID:Phencyclidine-induced rotational behavior in rats with nigrostriatal lesions and its modulation by dopaminergic and cholinergic agents. 1 84

To understand the mechanism of the action of ATP on the in vitro transport of the rapidly-labeled RNA from isolated nuclei, the fate of ATP during the incubation as well as the effect of ATP, its analogues and other ribonucleoside triphosphates on the transport was examined and the following results were obtained. (1) More than 97% of added ATP remained acid soluble. No polyadenylation of the rapidly-labeled RNA in the released fraction by added ATP occurred although new polyadenylate segments smaller than 10 S were synthesized. (2) The addition of an ATP-generating system to the reaction mixture restored the initial rate of the release of the rapidly-labeled RNA from isolated nuclei. (3) Among the ribonucleoside triphosphates tested, ATP was most effective in stimulating the release. GTP was about 2/3 as effective as ATP. UTP showed some effect, but CTP showed no effect. EDTA was also non-effective. (4) When no ATP-generating system was added to the reaction mixture, AMP failed to mimic the effect of ATP. However, the combination of AMP and pyrophosphate could take the place of ATP. (5) Both AMP-CPP and AMP-PCP, the ATP analogues, showed the equal degree of their effect on the release, regardless of the position of the methylene bond. From these results, the principal role of ATP in the in vitro transport systems seemed to be its interaction with isolated nuclei to dissociate a structure which retains the rapidly-labeled RNA in the nucleus.
Biochim Biophys Acta 1978 Dec 21
PMID:The role of ATP in the transport of rapidly-labeled RNA from isolated nuclei of rat liver in vitro. 10 29

Violence associated with chronic phencyclidine (PCP) abuse was investigated by administering a structured interview to 16 chronic PCP abusers. A more intensive study was done of another individual who committed murder and self-mutilation under the influence of PCP. The results suggest that there is no consistent association between PCP-related violence and a history of violence not related to drug or alcohol abuse. The author defines four types of violence associated with chronic PCP abuse.
Am J Psychiatry 1979 Dec
PMID:Violence associated with phencyclidine abuse. 50 11

The effects of acute IP administration of phencyclidine (PCP), d-amphetamine (AMPH) and pentobarbital (PB) were determined in 10 mice trained to lever press on a differential reinforcement of low rate 10 sec schedule of sweetened milk presentation. The effects of PCP were highly consistent, with large response rate increases (and a corresponding shift toward shorter interresponse times) at doses of 1 and 3 mg/kg. Higher doses generally decreased response rates and resulted in a bimodal interresponse time distribution. The effects of AMPH were similar to PCP but less consistent. Although some of the subjects showed substantial response rate increases at doses between 0.3 and 10 mg/kg, half of the subjects did not show increased response rates at any dose. The effects of AMPH on the interresponse time distribution were similar to PCP. The effects of PB were least like those of PCP. The effect in most subjects was to produce a dose-related decrease in response rate and a flattening of the interresponse time distribution. Occasional small response rate increases were observed with PB.
Pharmacol Biochem Behav 1979 Dec
PMID:Effects of phencyclidine, d-amphetamine and pentobarbital on spaced responding in mice. 53 50

The abuse of phencyclidine [1(1-phencylohexyl)piperidine, PCP], commonly referred to as angel dust or hog, is rapidly reaching epidemic proportions. PCP users often appear violent and increases in PCP-implicated homicides and suicides have been reported. In animal studies PCP has been demonstrated in brain up to 48 h after administration, long after blood levels become undetectable. However, there is little further information on the distribution of PCP within the central nervous system with regard to the possible sites of action. Recently, Sokoloff and associates described a new technique which can be used to visualise possible sites of drug action. The technique is based on the premise that neuronal activity is closely related to energy metabolism. Therefore, by directly monitoring 2-deoxy-D-glucose consumption before and after a pharmacological stimulus, we can obtain autoradiographic evidence of changes in neuronal activity in discrete areas brain as a response to that stimulus. Using this procedure, we now report that PCP causes dramatic changes in glucose metabolism in very specific regions of the rat brain.
Nature 1979 Dec 06
PMID:Localisation of phencyclidine-induced changes in brain energy metabolism. 55 Dec 94

The novel semirigid derivatives (+)-cis-1-[2-phenyl-2-bicyclo[3.1.0]hexyl]piperidine [(+)-8], its enantiomer (-)-8, and (+-)-trans-1-[2-phenyl-2-bicyclo[3.1.0]hexyl]piperidine [(+/-)-9] were synthesized as probes to investigate the mode of interaction of phencyclidine (PCP) with its binding site on the N-methyl-D-aspartate receptor complex. Each target compound was obtained in five steps starting from cyclopent-2-enone. (+)- and (-)-8 were obtained in greater than 98% optical purity through three recrystallizations from ethanol of the (S)-(+)- and (R)-(-)-mandelate salts of intermediate (+-)-cis-2-phenyl-2-bicyclo[3.1.0]hexylamine ([(+/-)-16]. Crystallization of the (R)-(-)-mandelate salt afforded (1R,2R,5S)-(-)-16, whereas the (S)-(+)-mandelate salt afforded (1S,2S,5R)-(+)-16; the absolute configuration was determined by single-crystal X-ray analysis of (-)-16.(R)-(-)-mandelate. Single-crystal X-ray analysis of (+/-)-9-picrate confirmed its trans configuration and provided conformational data. (+)- and (-)-8 and (+/-)-9 were examined for their ability to interact with PCP and sigma binding sites in vitro using [3H]TCP and [3H]pentazocine as radioligands. The binding was compared with that of PCP and contrasted with the rigid symmetrical phencyclidine derivatives cis- and trans-1-[3-phenyl-3-bicyclo[3.1.0]hexyl]piperidines (6 and 7). The results of the study indicated that the conformations of PCP represented by 6-9 are not optimal for potent interaction at either of these sites. Affinities ranged from 582 nM [(+/-)-9] to 29,000 nM [(+)-8] at PCP binding sites and from 1130 nM [(-)-8] to 16,300 nM (7) at sigma sites. In this assay, PCP exhibited affinities of 64.5 nM at PCP and 1090 nM at sigma sites. Qualitative correlation between the sigma and PCP binding data suggests some similarities between these binding sites. An axial phenyl and equatorial piperidine ring with the nitrogen lone pair of electrons antiperiplanar to the phenyl ring has been postulated as the receptor-active conformation of PCP-like ligands at the PCP binding site. Comparison of the binding data of 7-9 with that of the previously described methylcyclohexyl-PCP derivatives allowed its rationalization in terms of this model. It is likely that the lowered affinity in this bicyclo[3.1.0]hexane series is a consequence of nonoptimal geometry (pseudoequatorial phenyl or pseudoboat) for binding as opposed to the presence of steric bulk which proved deleterious in the methylcyclohexyl-PCP derivatives.
J Med Chem 1992 Dec 11
PMID:Synthesis, configuration, and activity of isomeric 2-phenyl-2-(N-piperidinyl)bicyclo[3.1.0]hexanes at phencyclidine and sigma binding sites. 146 99

The non-competitive NMDA receptor antagonists, PCP (phencyclidine), MK801, and ketamine produce psychosis in humans and abnormal vacuoles in posterior cingulate and retrosplenial rat cortical neurons. We show that PCP (> or = 5 mg/kg), MK801 (> or = 0.1 mg/kg), and ketamine (> 20 mg/kg) induce hsp70 mRNA and HSP70 heat shock protein in these vacuolated, injured neurons, and PCP also induces hsp70 in injured neocortical, piriform, and amygdala neurons. The PCP, MK801, and ketamine drug induced injury occurs in 30 day and older rats, but not in 0-20 day old rats, and is prevented by prior administration of the antipsychotic drugs haloperidol and rimcazole. Since haloperidol and rimcazole block dopamine and sigma receptors, and since M1 muscarinic cholinergic receptor antagonists also prevent the injury produced by PCP, MK801, and ketamine, future studies will be needed to determine whether dopamine, sigma, M1, or other receptors mediate the injury.
J Neurosci Res 1992 Dec
PMID:Haloperidol prevents induction of the hsp70 heat shock gene in neurons injured by phencyclidine (PCP), MK801, and ketamine. 148 94

The psychotomimetic effects of certain cycloalkyls and benzomorphans that interact with sigma receptors has led to the hypothesis that these sites may be important in the etiology of schizophrenia. DuP 734 [1-(cyclopropylmethyl)-4-(2'-(4''-fluoro-phenyl)-2'-oxoethyl) piperidine HBr] is a novel sigma receptor ligand. The receptor binding specificity and neuroanatomical distribution of [3H]DuP 734-labeled sigma receptors in guinea pig brain were examined using quantitative autoradiography. [3H]DuP 734 binding (10 microM haloperidol displaceable) to slide-mounted sections of guinea pig brain was saturable and of high affinity (Ki = 3.9 nM). Competition studies, under conditions identical to those used to visualize the receptor, yielded the following rank order of potency: DuP 734 > haloperidol > (+)-pentazocine > (-)-butaclamol > DTG > (+)-SKF 10,047 > (+)-3-PPP > (-)-pentazocine > (+)-butaclamol > U50,488H > (-)-SKF 10,047 > cinanserin > PCP >> MK801, sulpiride. High densities of [3H]DuP 734 binding sites displaceable by haloperidol were present in the limbic system, in particular the dorsal and ventral bands of Broca as well as the ventral pallidum. Within the hippocampus, the pyramidal layers were sparsely labeled, while higher densities of binding sites were evident in the dentate gyrus. The frontal cortex, the mammillary complex of the hypothalamus, the central gray and red nucleus of the midbrain, the pontine reticular nucleus, the Purkinje cell layer of the cerebellum and dorsal and ventral horns, as well as the central gray matter of the spinal cord, all showed enrichments of [3H]DuP 734 binding sites. Lower levels of binding were present in the other regions of the cerebral cortex including parietal, pyriform, occipital, cingulate cortex, as well as the basal ganglia, and negligible specific binding was present in the white matter tracts. The kinetic and pharmacological characteristics and distribution of [3H]DuP 734 binding sites in brain are similar to those previously reported for sigma receptors.
Brain Res 1992 Dec 11
PMID:Autoradiographic identification and characterization of sigma receptors in guinea pig brain using [3H]1(cyclopropylmethyl)-4-(2'-(4''-fluorophenyl)-2'-oxoethyl) piperidine ([3H]DuP 734), a novel sigma receptor ligand. 148 5

Wall climbing behavior is an age-specific behavior that is elicited during postnatal Days 7 through 17 by various stimuli that include heat, odors, shock, and the catecholaminergic agonists apomorphine, amphetamine, and clonidine. In a previous study, a significant amount of wall climbing behavior was observed during ataxia and activity testing following phencyclidine (PCP) administration in Day 19 but not Day 40 rat pups. The present study describes the ontogeny of PCP-induced wall climbing behavior and locomotor activity. Frequency and duration of wall climbing bouts and locomotor activity were recorded on Days 5, 12, 19, 26, 33, or 40 following PCP treatment. On Day 12, all doses of PCP induced significant amounts of wall climbing behavior. A similar pattern of results was observed on Day 5 although these effects were not statistically significant. After Day 12, PCP-induced wall climbing behavior declined precipitously. PCP increased locomotor activity at all ages tested with maximum activities observed on Day 19. These results demonstrate that PCP-elicited wall climbing behavior follows an ontogenetic profile similar to that previously reported for other stimuli and that there are robust ontogenetic differences in the locomotor response to PCP.
Dev Psychobiol 1992 Dec
PMID:The ontogeny of phencyclidine-induced wall climbing and locomotor activity. 148 84

As the AIDS epidemic progresses, the number of ED patients with HIV-related illness will continue to increase. As reviewed in this article, much of the existing clinical research in HIV-related illness has an impact on the diagnostic and management issues that arise in the ED. Many of the patterns of disease, subtleties of diagnosis, and therapies unique to AIDS patients have already been greatly elucidated. However, as the recognition of this disease goes into only its second decade, many questions remain. Further studies are needed, for example, to improve physician assessment of HIV risk, to further identify discriminators of PCP and bacteremia, and to optimize strategies for disposition and outpatient management. In the future, in the areas of research and clinical care, emergency medicine will play an increasing important role in the front-line attack on this modern epidemic.
Ann Emerg Med 1991 Dec
PMID:The management of HIV-related illness in the emergency department. 166 Jun 80


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