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 several cerebroprotective and nootropic drugs on the function of excitatory amino acid (EAA) receptor subtypes expressed in Xenopus oocytes after injection of rodent brain poly(A)+ mRNA were investigated. The oocyte response to N-methyl-D-aspartate (NMDA) in the presence of glycine (Gly) was inhibited dose-dependently by bifemelane, indeloxazine, vinpocetine and vincamine while no effect was observed by idebenone, Ca hopantenate, aniracetam or piracetam. Bifemelane, indeloxazine and vinpocetine suppressed the maximum response of NMDA and Gly without affecting their EC50 values. Unlike Mg2+, they did not affect the current-voltage relationship of the NMDA response below 0 mV. On the non-NMDA-type responses of the injected oocytes to kainate (KA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) and quisqualate (QA), no significant effects were observed by these drugs at 100 microM. On the binding of [3H](+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imi ne (MK-801) to brain membranes, the estimated IC50 values were 88 microM for bifemelane, 102 microM for indeloxazine, and 115 microM for vinpocetine. The dissociation rate of [3H]MK-801 was significantly slowed by Zn2+ and vinpocetine, but not affected by bifemelane or indeloxazine. The Kd value for [3H]MK-801 binding was increased by bifemelane and indeloxazine while Bmax was unchanged. These results suggest that the inhibition of NMDA channels by vinpocetine shows a similarity to the action of Zn2+ which closes the gate of the NMDA channel. In contrast, bifemelane and indeloxazine may affect the phencyclidine (PCP)-site in the open channels and inhibit NMDA function.
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PMID:Effects of several cerebroprotective drugs on NMDA channel function: evaluation using Xenopus oocytes and [3H]MK-801 binding. 165 46

The kinetic and equilibrium binding of various tritiated phencyclidine (PCP)-like drugs to the N-methyl-D-aspartate (NMDA) receptor of rat brain cortex were analyzed and compared. The tested drugs showed the following rank order of affinity toward the receptor: [3H](+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imi ne maleate ([3H]MK-801) greater than [3H]-N-[1-(2-thienyl)cyclohexyl]piperidine ([3H]TCP greater than [3H]-N[1-(3-aminophenyl)cyclohexyl]piperidine ([3H]NH2PCP) greater than [3H]phencyclidine ([3H]PCP) greater than [3H]-N[1-(3-azidophenyl)cyclohexyl]piperidine ([3H]AZ-PCP) greater than [3H]-N-[1-(3-nitrophenyl)cyclohexyl]piperidine ([3H]NO2PCP) (Kd = 3, 10, 24, 35, 100 and 2500 nM, respectively). All of the labeled ligands were found to associate with and dissociate from the receptor; both processes occurred at relatively slow rates in the absence of added glutamate and its allosteric effector glycine (basal binding) but were markedly accelerated upon their addition. For each drug, the basal association rate was similar to the basal dissociation rate. However, the basal rates differed markedly among the different drugs tested, and their apparent time constants characterizing the first-order process of basal ligand binding (kb) correlated inversely with their equilibrium binding constants (KD). The recorded kb values (10(-3) min-1) were 2.3, 5.1, 12.4, 44 and 79 for [3H]MK-801, [3H]TCP, [3H]NH2PCP, [3H]PCP and [3H]AZ-PCP, respectively. The glutamate- and glycine-induced dissociation rates (characterized by the apparent time constant k-1) differed among the ligands and also correlated inversely with their KD values. Their induced association rates, however, were similar.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Distinctive structural requirement for the binding of uncompetitive blockers (phencyclidine-like drugs) to the NMDA receptor. 215 15

Early catheterisation was performed in 27 patients with an acute inferior myocardial infarction less than 3 days old complicated by signs of low output with right ventricular dysfunction. All patients had hemodynamic criteria of adiastole (PCP = 14.9 +/- 31 mmHg and LVEDP = 14.1 +/- 4.7 mmHg) with low cardiac output (CI = 1.41 +/- 0.32 l/min/m2). An atropine resistant bradycardia was characteristic (HR = 65 +/- 17.2/min) due to advanced or complete AV block (11 cases), sinoatrial block (3 cases, one with right atrial standstill) or sinus/parasinus rhythm (13 cases) inappropriate to the severity of their hemodynamic state. Although the prognosis based on the discriminating linear function FI = -0.427 + 0.00121 LVW - 0.00125 TPR was initially poor and predicted the death of 21 out of the 27 patients at one month, the outcome was usually favourable and only 8 patients died during the first month. Fifteen patients were treated by temporary endocavitary RV pacing. As the heart rate was increased from 53.8 +/- 11.2 to 92.4 +/- 4.9/min, the CI rose from 1.35 +/- 0.26 to 1.85 +/- 0.46 l/min/m2 (p less than 0.001) with a fall in SI from 26.7 +/- 8.3 to 20.1 +/- 5.6 ml/beat/m2 (p less than 0.005). The results were even further improved in 3 cases by sequential A-V pacing. The observed hemodynamic improvement continued during the period of pacing providing volumic expansion maintained LVEDP above 10 mmHg.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The value of temporary electrosystolic pacing for treating low output in posterior necrosis with adiastole]. 641 96

The pharmacological characteristics and the regional distribution of [3H]3-OH-PCP (1-[1(3-hydroxyphenyl)-cyclohexyl]piperidine) binding were investigated in rat brain by quantitative autoradiography. Kinetic analysis of [3H]3-OH-PCP binding revealed fast and slow components, in the association and dissociation studies. The regional distribution of binding closely corresponded to those of binding sites labeled by [3H]N-[l-(2-thienyl)-cyclohexyl]3,4-piperidine (TCP) and [3H](+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imi ne maleate (MK 801). High densities of [3H]3-OH-PCP binding sites were found in the stratum radiatum and orients of field CA1 in the hippocampus and in the outer layers of cerebral cortices. In contrast, low levels of binding were seen in the brain stem and the granular cell layer of the cerebellum. [3H]3-OH-PCP binding was strongly inhibited by MK 801 and 3-OH-PCP, while the potency of (+)-SKF 10047 in inhibiting [3H]3-OH-PCP binding was less in the cerebral cortex and hippocampus. The antagonists for the glutamate, glycine and polyamine recognition sites at the NMDA/PCP receptor complex displaced [3H]3-OH-PCP binding sites with a potency similar to that of [3H]MK 801. These findings suggest that the [3H]3-OH-PCP binding site is similar or identical to the PCP binding site labeled by [3H]TCP and [3H]MK 801.
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PMID:Autoradiographic study on the pharmacological characteristics of [3H]3-OH-PCP binding sites in rat brain. 888 23