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)

PCP-GABA, an analogue of the neurotransmitter amino acid, GABA, is as effective a stimulant of vagal centers and acid secretion as sham feeding. Insulin hypoglycemia, a test hitherto widely used for the cephalic phase, is unsafe and nonspecific because it also stimulates catecholamine release which affects gastrin secretion. PCP-GABA, unlike insulin, causes no tachycardia or hypoglycemia; however, the major advantage of PCP-GABA is that it can be used safely intraoperatively to assess completeness of vagotomy. Its muscle relaxant action is an additional advantage in this regard. As an intraoperative test, PCP-GABA is given intravenously shortly after induction of anesthesia to stimulate acid secretion and to reduce gastric mucosal pH, which is measured by an intraluminal combination electrode. The electrode can be moved around through the intact gastric wall to take measurements from multiple sites. When vagotomy is complete, gastric mucosal pH increases to over 6. This test works well in the dog. We hope to assess its clinical use in the near future.
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PMID:A new intraoperative test for completeness of vagotomy: the PCP-GABA (beta-parachlorophenol-gamma-aminobutyric acid) test. 636 46

In 1,000 cases of phencyclidine (PCP) intoxication evaluated at the time of first examination in an emergency department, the incidence of "typical" findings was found to be lower than has been reported previously. Nystagmus and hypertension occurred in only 57% of our cases; some patients had only one of these findings and many had neither. The incidence of violence was 35%; bizarre behavior, 29%; and agitation, 34%. Changes in sensorium consisted of coma, lethargy/stupor, and acute brain syndrome; however, 46% of patients were alert and oriented. Motor signs included grand mal seizures, generalized rigidity, localized dystonias, catalepsy, and athetosis. Profuse diaphoresis, hypersalivation, bronchospasm, and urinary retention occurred in less than 5%. A small percentage had severe disturbances in vital signs, including three cases (0.3%) of cardiac arrest and 28 cases (2.8%) of apnea. Hypoglycemia and elevated serum CPK, uric acid, and SGOT/SPGT were common. Urine PCP levels did not correlate with the severity of the clinical findings.
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PMID:Acute phencyclidine intoxication: incidence of clinical findings in 1,000 cases. 722 71

Substantiating evidence has raised the possibility that sigma ligands may have therapeutic potential as neuroprotective agents in brain ischemia. It has been suggested that the neuroprotective capacity of sigma ligands is related primarily to their affinity for the NMDA receptor complex and not to any selective action at the sigma binding site. However, sigma specific ligands, devoid of significant affinity for the NMDA receptor, are also neuroprotective via an inhibition of the ischemic-induced presynaptic release of excitotoxic amino acids. In the present study, we have investigated the potential neuroprotective effect of a comprehensive series of sigma ligands, with either significant (sigma/PCP) or negligible (sigma) affinity for the PCP site of the NMDA receptor, in order to delineate a selective sigma site-dependent neuroprotective effect. For this aim, we have employed two different neuronal culture toxicity paradigms implicating either postsynaptic-mediated neurotoxicity, (brief exposure of cultures to a low concentration of NMDA or Kainate) or pre- and postsynaptic mechanisms (exposure to hypoxic/hypoglycemic conditions). Only sigma ligands with affinity for the NMDA receptor [(+) and (-) cyclazocine, (+) pentazocine, (+) SKF-10047, ifenprodil and haloperidol] were capable of attenuating NMDA-induced toxicity whereas the sigma [(+)BMY-14802, DTG, JO1784, JO1783, and (+)3-PPP] and kappa-opioid [CI-977, U-50488H] ligands, with very low affinity for the NMDA receptor, were inactive. The rank order of potency, based on the 50% protective concentration (PC50) value, of sigma/PCP ligands against NMDA-mediated neurotoxicity correlates with their affinity for the PCP site of the NMDA receptor, and not with their affinity for the sigma site. In addition sigma/PCP, sigma or kappa-opioid ligands failed to attenuate kainate-mediated neurotoxicity. On the other hand, sigma/PCP, sigma and kappa-opioid ligands were potent inhibitors of hypoxia/hypoglycemia-induced neurotoxicity, although their neuroprotective potency did not correlate with their affinity for either the sigma or PCP binding sites. In conclusion, the ability of sigma and kappa-opioid ligands to attenuate hypoxia/hypoglycemia, but not NMDA or kainate-induced toxicity, suggests that these drugs exert their neuroprotective role by a predominantly presynaptic mechanism possibly by inhibiting ischemic-mediated glutamate release.
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PMID:Distinct neuroprotective profiles for sigma ligands against N-methyl-D-aspartate (NMDA), and hypoxia-mediated neurotoxicity in neuronal culture toxicity studies. 779 19

The mechanisms of sigma (sigma) receptor ligands-induced neuroprotective effects are controversial because both sigma receptors and phencyclidine (PCP) binding sites of the N-methyl-D-aspartate (NMDA) receptor channel complex have been reported to contribute to these neuroprotective effects. Thus, to clarify the role of sigma receptor in the neuroprotective effects, we examined the effects of 1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine dihydrochloride (SA4503), a novel sigma1 receptor agonist with negligible affinity for the NMDA/PCP receptor channel complex, on the hypoxia/hypoglycemia- and exogenously applied NMDA-induced neurotoxicity in the rat primary neuronal cultures. A selective sigma1 receptor agonist, SA4503, significantly suppressed the hypoxia/hypoglycemia-induced neurotoxicity in the cultures, whereas this agonist failed to inhibit the NMDA-induced neurotoxicity. Similarly, (+)-pentazocine ((+)-PTZ), a prototype sigma1 receptor agonist, inhibited the hypoxia/hypoglycemia-induced neurotoxicity, whilst it did not affect the NMDA-induced toxicity in the cultures. These neuroprotective effects of SA4503 and (+)-PTZ were partially blocked by N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]ethylamine monohydrochloride (NE-100), a putative sigma1 receptor antagonist. These results suggest that the sigma1 receptor subtype plays an important role in the sigma receptor ligands-induced neuroprotective effects via the regulation of excitatory amino acids (EAAs) release from the presynaptic sites.
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PMID:Activation of sigma1 receptor subtype leads to neuroprotection in the rat primary neuronal cultures. 959 56

The largely empirical dopamine theory has limited value in clarifying the pathogenesis of schizophrenia, due to its inability to explain consistent imaging findings, such as cortical grey matter loss, reduced frontal and thalamic activity, and, reduced D1 receptor load. Furthermore, the most effective drug for treating positive and negative symptoms - clozapine - has minimal dopaminergic activity. We present an alternative hypothesis centring on presumed deficits in membrane bound glucose transporter proteins GLUT 1 and GLUT 3, either in absolute numbers or functional capacity. In situations of high demand, intracellular hypoglycaemia in neurones and astrocytes will produce acute symptoms of misperceptions, misinterpretations, anxiety and irritability - the usual features of prodromal and first onset schizophrenia. Furthermore, reduced glucose uptake will disrupt production of glutamate--functionally similar to the schizophrenia-like syndrome produced by PCP, a glutamate antagonist. In the longer term, reduced neuronal growth and poor synaptic contacts will produce chronic cognitive difficulties and perpetuate acute symptoms. A backlog effect due to reduced brain uptake of glucose would produce systemic hyperglycaemia observed in drug nai ve subjects. Rat studies have shown that clozapine and similar compounds block GLUT proteins in the brain and peripherally, more so than selective dopamine blockers. By blocking GLUT proteins, clozapine would break malfunctioning circuits, resulting in the disappearance of cognitive and perceptual symptoms. Unfortunately, these drugs would also raise systemic glucose levels, increasing the risk of diabetes, as observed in longer term studies of clozapine in particular. We summarise potentially useful research strategies, including studying the genotype of GLUT proteins with respect to schizophrenia phenotypes, activation studies involving fMRI using deoxyglucose as a substrate, and investigating clinical features of schizophrenic patients prior to and following treatment for co-existing diabetes.
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PMID:Impaired neuronal glucose uptake in pathogenesis of schizophrenia - can GLUT 1 and GLUT 3 deficits explain imaging, post-mortem and pharmacological findings? 1612 30