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)

This study was designed to determine the action sites of phencyclidine (PCP) involved in the development of behaviors such as head-weaving, immobility, turning and backpedalling in relation to dopaminergic and serotonergic neuronal functions. Injection of PCP into the caudate nucleus or prefrontal cortex dose-dependently produced head-weaving, although the injection of PCP into the nucleus accumbens failed to produce head-weaving. The intensity of head-weaving induced by injection of PCP into the prefrontal cortex was relatively high when compared to that induced by injection of PCP into the caudate nucleus or lateral ventricle. Pretreatment with p-chlorophenylalanine (300 mg/kg), a serotonin (5-HT) synthesis inhibitor, attenuated head-weaving induced by injection of PCP into the prefrontal cortex. Injection of PCP (50-100 micrograms) into the prefrontal cortex also produced immobility for 5 min post-injection. Rats pretreated with pimozide (1 mg/kg), a dopamine (DA) antagonist, also produced immobility after the injection of PCP into the prefrontal cortex and this effect was attenuated by pretreatment with ritanserin, a 5-HT2 receptor antagonist. On the other hand, pretreatment with methamphetamine attenuated PCP (5 and 7.5 mg/kg)-induced turning and backpedalling but not head-weaving. Pretreatment with large doses of apomorphine, a DA agonist, also greatly attenuated PCP (7.5 mg/kg)-induced behaviors, i.e. head-weaving, turning and backpedalling. These effects of DA agonists were prevented by haloperidol (0.25 mg/kg), a DA antagonist. These results suggest that PCP-induced turning and backpedalling may be mediated by reducing dopaminergic transmission, although PCP-induced head-weaving and immobility may be produced by increasing serotonergic transmission in the prefrontal cortex.
J Pharmacobiodyn 1986 Dec
PMID:Role of dopaminergic and serotonergic neuronal systems in the prefrontal cortex of rats in phencyclidine-induced behaviors. 357 18

The effects of chronic phencyclidine (PCP) or ketamine (KET) on their respective acute behavioral and anticonvulsant actions were investigated. Female rats were treated for 15 days with twice daily i.p. injections of saline, 20 mg/kg PCP or 40 mg/kg KET. Subjects treated chronically with PCP were challenged with either 10 mg/kg or 20 mg/kg i.p. PCP, while subjects treated chronically with KET were challenged with 40 mg/kg i.p. KET only. Neither chronic drug treatment induced tolerance to the acute anticonvulsant effect, nor to hyperlocomotion and stereotypy as measured by automated activity monitors. However, evidence of tolerance to the stereotypy induced by acute KET was obtained when an observer-based rating scale was employed. In addition, tolerance occurred to the ataxia induced by KET and the 10 mg/kg, but not 20 mg/kg, dose of PCP. Thus, tolerance occurs to some of the acute behavioral effects of PCP and KET while the anticonvulsant action of these compounds remains unaffected.
Behav Brain Res 1986 Dec
PMID:The anticonvulsant and behavioral effects of phencyclidine and ketamine following chronic treatment in rats. 379 Feb 47

In rats trained to discriminate the prototypic sigma receptor agonist, (+)-N-Allylnormetazocine [(+)-N-Allylnormetazocine [(+)-NANM/SKF 10,047], from saline, the (+)- but not the (-)-isomer of 3-(3-hydroxyphenyl)-N-(1-propyl)piperidine (3-PPP) produced (+)-NANM-like discriminative stimuli. (+)-3-PPP binds stereo selectively to the (+)-NANM binding site, but not to the phencyclidine binding site. Additionally, phencyclidine was found to produce (+)-NANM-like discriminative stimuli. Although the 3-PPP isomers were shown to produce changes in central dopaminergic activity (Hjorth et al. Life Sci 37, 673, 1985), the discriminative stimulus properties of (+)-3-PPP are apparently not mediated via the dopaminergic system. This hypothesis is supported by the fact that apomorphine did not produce (+)-NANM-like discriminative stimuli. These stimuli are thus non-dopaminergic and may be due to the (+)-3-PPP actions at the sigma binding site. However, it is possible that (+)-NANM, PCP, and (+)-3-PPP may have common non-sigma pharmacologic properties that account for the similar discriminative stimulus properties of these compounds.
Life Sci 1986 Dec 29
PMID:(+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine [(+)-3-PPP] but not (-)-3-PPP produces (+)-N-allylnormetazocine-like (SKF 10,047) discriminative stimuli. 379 7

Five infants and two young children were treated at a large children's hospital for phencyclidine intoxication. The clinical symptoms and signs were mostly neurologic, including diminished response to tactile and verbal stimuli (100%), ataxia (71%), nystagmus (57%), constricted pupils (57%), depressed sensorium, and stupor associated with a blank, expressionless stare (57%). Notably absent were the behavioral aberrations such as aggression, which are usually seen with PCP intoxication in older children and adults. The possibility of drug intoxication was denied by most of the parents or surrogate parents accompanying these small children and infants for treatment. It is suggested that a systematic investigation for possible PCP exposure, including a urine toxicology screen for PCP (preferably by immunoassay methods), be conducted whenever an infant or child is brought for emergency treatment of unresponsiveness, bizarre behavior, dyskinesis, dystonic posturing, atypical oculomotor and pupil findings, or evidence of hallucinations.
Pediatr Emerg Care 1986 Dec
PMID:PCP intoxication in seven young children. 379 69

Amphetamine (1.0-7.0 mg/kg), cocaine (5.0-40.0 mg/kg) and phencyclidine (1.0-7.0 mg/kg) increased acoustic startle responding in mice. These drugs, however, had varying effects on habituation of the startle response after repeated exposure to the auditory stimulus. The primary effect of phencyclidine was to disrupt the habituation process, whereas increased startle responding after cocaine developed without modification of the habituation curve. Amphetamine facilitated acoustic startle at all doses, and after administration of 3.0 mg/kg a significant response sensitization as a function of repeated stimulus presentation was evident. Consistent with previous reports the excitatory effects of cocaine and amphetamine on acoustic startle were blocked by pretreatment with haloperidol. Haloperidol, which decreased startle responding, attenuated the facilitating effects of PCP on acoustic startle as well. Chronic exposure to amphetamine, cocaine and phencyclidine had differential effects on startle responding. The facilitating effects of amphetamine on startle were further enhanced after long-term exposure to the drug and the sensitizing effect of repeated amphetamine exposure was observed only when animals were tested with amphetamine. In contrast, tolerance developed after chronic exposure to both cocaine and phencyclidine, and the response attenuation was evident when animals were tested for acoustic startle after cocaine, amphetamine and phencyclidine.
Pharmacol Biochem Behav 1986 Dec
PMID:Sensitization to amphetamine and tolerance to cocaine and phencyclidine stimulation in mice. 380 18

The enthalpy changes that occur in the self-assembly of tubulin into microtubules were examined by adiabatic differential heat capacity microcalorimetry and by isothermal batch microcalorimetry. Tubulin solutions at concentrations between 7 and 17 mg/mL were heated from 0 to 40 degrees C at heating rates of 1 or 2 deg/min in pH 6.8 or 7.0 assembly buffers containing 20 mM MES, 100 mM glutamic acid, 5 mM MgCl2, 3.4 M glycerol, and either 0.5 mM GMP-PCP or 1 mM GTP. The assembly reaction in the presence of GTP was characterized by a complex heat-uptake pattern consisting of a broad endotherm with a sharper exotherm superimposed on it, similar to assembly in a GTP phosphate buffer [Hinz, H.-J., Gorbunoff, M.J., Price, B., & Timasheff, S.N. (1979) Biochemistry 18,3084]. Replacement of GTP by the nonhydrolyzable analogue resulted in a pattern typical for an endothermic reaction only. These results have permitted the assignment of the endothermic process to microtubule assembly and of the exothermic process to the resultant GTP hydrolysis. In these studies equilibration was found to be slow, several hours of cooling being required for the system to return to its original state. Turbidity scans also revealed hysteresis between consecutive scans and a displacement of the depolymerization transition midpoint to a lower temperature than that of assembly. The disassembly of microtubules was examined in batch calorimetry experiments in pH 7.0 phosphate, 1 mM GTP, 16 mM MgCl2, and 3.4 M glycerol, in which tubulin assembled into microtubules was diluted to below the critical concentration.(ABSTRACT TRUNCATED AT 250 WORDS)
Biochemistry 1986 Dec 16
PMID:Enthalpy changes in microtubule assembly from pure tubulin. 381 84

With regard to Starling's equation, two factors are important for fluid regulation in pulmonary tissue: colloid osmotic pressure (COP) and hydrostatic pressure (PCP). The purpose of the study was to evaluate the relationship between COP, COP-PCP-gradient and extravascular lung water (EVLW) immediately after extracorporeal circulation (ECC). 39 consenting patients undergoing elective aorto-coronary bypass surgery received 1000 ml washed erythrocytes (w.e.; cell saver) +400 ml fresh frozen plasma (FFP) after ECC. Additionally, group I (n = 15) received 300 ml albumin 20%, group II (n = 13) 500 ml plasmaexpander (3% HES 200/0.5) and group III (n = 11) no more volume. At three different times, measurement of EVLW was performed by using double-indicator-dilution technique with indocyanine green and a microprocessed lung water computer: 15 minutes after ECC (before infusion), 45 minutes after ECC (after infusion), five hours after ECC. Application of 20% albumin led to a significant increase in COP (+67%) which was less pronounced in group II (+40%) and group III (+41%). Simultaneously, the most pronounced increase in EVLW could be observed in group I (+25%) as well. Pulmonary gas exchange in group I was more compromised (PaO2 -72 mmHg) than in group II (-38 mmHg) and group III (-50 mmHg). No correlation between EVLW and COP-PCP-gradient could be observed. In spite of a significant elevation of COP by using 20% albumin solution, EVLW increased with subsequent deterioration of pulmonary gas exchange. The presented data demonstrate no advantage of albumin 20%; if volume substitution is necessary after ECC, low concentrated plasmaexpanders (up to 10 ml/kg b.w.) may be preferred for several reasons.
Herz 1985 Dec
PMID:[Colloid osmotic pressure and extravascular lung water following extracorporeal circulation]. 387 22

Newborn Holstein bull calves were fed either analytical pentachlorophenol (aPCP) or technical pentachlorophenol (tPCP) for 6 wk to establish and compare the clinical and pathologic manifestations of toxicity. Four groups of three calves/group were each fed either 1 or 10 mg X (kg body weight)-1 X d-1 of either aPCP or tPCP. A fifth group served as control. Dosages of both PCP preparations were normalized to contain equal concentrations of PCP. Toxic effects were observed only at the 10 mg/kg dose in the tPCP-treated calves. These effects included decreased body weight gain, anorexia, decreased serum protein concentration, elevated serum gamma glutamyl transferase, and decreased triiodothyronine (T3) and thyroxine (T4) concentrations. Histologic lesions included cortical atrophy in the thymus and squamous metaplasia and hyperkeratous changes in the Meibomian gland of the eyelid. Thyroid function, which was assessed in vivo by measuring the rate of T3 and T4 production over 4 h after thyrotropin-releasing hormone (TRH)-challenge, was not impaired suggesting an extrathyroidal site of toxic action. Although serum chemistry indicators were suggestive of hepatic injury there were no discernable lesions. Organ weight analyses were inconclusive but there was a tendency toward enlargement of liver, kidneys and thyroid and decreased weight of lungs, spleen and thymus. A toxic effect clearly related to PCP and not its contaminants was depressed active transport of p-aminohippurate measured in kidney slices in vitro. Steady state concentrations of PCP in serum were about 40 and 90 ppm for the 1 and 10 mg/kg groups, respectively. Concentrations of PCP among the major organs were comparable.
J Anim Sci 1985 Dec
PMID:Assessment of pentachlorophenol toxicity in newborn calves: clinicopathology and tissue residues. 393 33

The isolated perfused lung (IPL) of rats were used to examine the pulmonary disposition and metabolism of radiolabeled phencyclidine (PCP) and N-ethyl-1-phenylcyclohexylamine (PCE). The IPL removed PCP and PCE from the perfusate and converted them to free and conjugated metabolites. At the conclusion of a 1-h perfusion, the lung accumulated at least 20% of the administered radioactivity and metabolized more than 30% of the added drug. Pretreatment of rats with 3-MC or cigarette smoke enhanced significantly PCP and PCE metabolism by the IPL. The concentration of conjugated PCE metabolite in the perfusate of the IPL was increased significantly by both 3-MC and cigarette smoke pretreatments whereas the concentration of conjugated PCP metabolite was not affected by cigarette smoke exposure and increased only slightly after 3-MC pretreatment. Pretreatment of rats with 3-MC or cigarette smoke also altered the amount of radioactivity accumulated by the lung tissue at the conclusion of a 1-h perfusion. Inasmuch as PCP and PCE are often abused by humans via smoke inhalation, a significant amount of these drugs may be stored or metabolized by the lung.
Toxicology 1985 Dec
PMID:Effects of cigarette smoke and 3-methylcholanthrene on the disposition of phencyclidine and its N-ethylamine analogue in the isolated perfused lung of rats. 407 55

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.
Am Fam Physician 1985 Dec
PMID:Management of PCP intoxication. 407 64


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