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)

Computer-assisted molecular modelling techniques and electrostatic analyses of a wide range of phenycyclidine (PCP) and sigma ligands, in conjunction with radioreceptor studies, were used to determine the topographies of the PCP and sigma receptors. The PCP receptor model was defined using key molecules from the arylcyclohexylamine, benzomorphan, bridged benz[f]isoquinoline, and dibenzocycloalkenimine drug classes. Hypothetical receptor points (R1, R2) were constructed onto the aromatic ring of each compound to represent hydrophobic interactions with the receptor, along with an additional receptor point (R3) representing a hydrogen bond between the nitrogen atom and the receptor. The superimposition of these key molecules gave the coordinates of the receptor points and nitrogen defining the primary PCP pharmacophore as follows: R1 (0.00, 3.50, 0.00), R2 (0.00, -3.50, 0.00), R3 (6.66, -1.13, 0.00), and N (3.90, -1.46, -0.32). Additional analyses were used to describe secondary binding sites for an additional hydrogen bonding site and two lipophilic clefts. Similarly, the sigma receptor model was constructed from ligands of the benzomorphan, octahydrobenzo[f]quinoline, phenylpiperidine, and diphenylguanidine drug classes. Coordinates for the primary sigma pharmacophore are as follows: R1 (0.00, 3.50, 0.00), R2 (0.00, -3.50, 0.00), R3 (6.09, 2.09, 0.00), and N (4.9, -0.12, -1.25). Secondary binding sites for sigma ligands were proposed for the interaction of aromatic ring substituents and large N-substituted lipophilic groups with the receptor. The sigma receptor model differs from the PCP model in the position of nitrogen atom, direction of the nitrogen lone pair vector, and secondary sigma binding sites. This study has thus demonstrated that the differing quantitative structure-activity relationships of PCP and sigma ligands allow the definition of discrete receptors. These models may be used in conjunction with rational drug design techniques to design novel PCP and sigma ligands of high selectivity and potency.
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PMID:Receptor site topographies for phencyclidine-like and sigma drugs: predictions from quantitative conformational, electrostatic potential, and radioreceptor analyses. 284 51

The effects of NIK-247 [9-amino-2,3,5,6,7,8-hexahydro-1H-cyclopenta(b)-quinoline monohydrate hydrochloride] were studied on a model involving various types of drug- and electroconvulsive shock (ECS)-induced amnesia. The step-down type passive avoidance task in mice was used for comparison of the effects with those of tacrine, a 4-aminopyridine derivative which has an antiamnesic action. NIK-247 administered pre- and post-training or pre-retention test (24 h after training) prevented the disruption of memory induced by cycloheximide administered immediately after training. In addition, NIK-247 protected from the amnesia induced by treatment with ECS, phencyclidine and picrotoxin immediately after training. Tacrine failed to protect from ECS- and PCP-induced amnesia at the doses effective on cycloheximide-induced amnesia. The results indicate that NIK-247 improves cognitive functions at different phases of the learning and memory processes such as acquisition, consolidation, and retrieval in drug- and ECS-induced amnesia. NIK-247 may produce its antiamnesic effects via the cholinergic and GABAergic neuronal systems.
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PMID:Effects of the novel compound NIK-247 on impairment of passive avoidance response in mice. 323 81

The capacity of human liver S9 and hepatocytes to metabolically activate 2-amino-3-methylimidazo (4,5-f) quinoline (IQ) in Salmonella mutagenicity assays more closely resembles that of preparations from Aroclor-induced rat than control rat. The extent to which hepatocyte conjugating enzymes contribute to activation in these assays has been studied. Omission of sulphate or addition of a 'specific' sulphotransferase inhibitor (2,6-DCNP) did not significantly reduce mutagenicity, nor did PAPS enhance S9-mediated bacterial mutagenicity. Conversely, mutagenicity was significantly inhibited by PCP (an inhibitor of both sulphotransferase and acetyltransferase) and an acetylation-deficient Salmonella (TA98/1,8DNP6) was unresponsive to the mutagenicity of IQ. These data suggest that acetylation but not sulphation is important in IQ bacterial mutagenesis. The addition of acetyl CoA, PAPS-generating system or ATP paradoxically reduces the mutagenicity of IQ in S9/Salmonella TA98 assays. Therefore, activation by esterification in hepatocytes does not contribute to the mutagenicity of IQ in Salmonella typhimurium possibly due to restricted access of conjugates into the bacterial cell.
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PMID:Activation of 2-amino-3-methylimidazo (4,5-f) quinoline in rat and human hepatocyte/Salmonella mutagenicity assays: the contribution of hepatic conjugation. 333 2