Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A group of original symmetrical and asymmetrical piperazine compounds containing ester function have been synthesized and pharmacologically characterized. All compounds are pharmacologically active. Some relationships between their chemical structure and biological activity are discussed. Analgesic and coronary dilatory and especially spasmolytic effects are marked for all asymmetrical esters. A number of the compounds are interesting for further investigations relative to their possible application in medical practice.
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PMID:Pharmacological study of the activity of a group of piperizine esters and changes in action relative to their chemical structure. 60 96

The neuronal dopamine transporter/uptake site can be covalently labeled with the photoaffinity probe 1-(2-[bis-(4-fluorophenyl) methoxy]ethyl)-4-[2-(4-azido-3-[125I]iodophenyl)ethyl]piperazine [( 125I]FAPP) and visualized following sodium dodecyl sulfate polyacrylamide gel electrophoresis and autoradiography. Upon photolysis, [125I]FAPP specifically incorporated into a polypeptide of apparent Mr = 62,000 in membranes from both the putamen and the caudate nucleus of control, Alzheimer's, schizophrenia, and Huntington's diseased brain, and following complete deglycosylation, migrated as an Mr approximately 48,000 polypeptide. In parkinsonian postmortem putamen, however, there was no detectable photoincorporation of [125I]FAPP into the ligand binding subunit of the dopamine transporter. [125I]FAPP did specifically label the Mr 62,000 polypeptide of parkinsonian caudate, although with efficiencies of 20-50% of control. The asymmetrical loss of the dopamine transporter in Parkinson's diseased striatum was confirmed in reversible receptor binding experiments using [3H]GBR-12935 (3H-labeled 1-[2-(diphenylmethoxy) ethyl]-4-(3-phenylpropyl)piperazine). In parkinsonian putamen, mazindol competitively inhibited the binding of [3H]GBR-12935 with an estimated affinity (Ki approximately 2,000 nM) 10 times lower than in controls (Ki approximately 30 nM), while the affinity of maxindol for [3H]GBR-12935 binding in the caudate was equal to that seen with controls (Ki approximately 50 nM). The proportion of [3H]GBR-12935 binding sites recognized by mazindol with high affinity in Parkinson's diseased caudate was, however, reduced by 50-80%.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The dopamine transporter is absent in parkinsonian putamen and reduced in the caudate nucleus. 198 18

Recent evidence indicates that when 1-(3-trifluoromethylphenyl)piperazine (TFMPP) is used as a training drug in the drug discrimination paradigm it produces a stimulus effect that is site-selective at the 5-HT1B receptor. The present study sought to employ this procedure in order to assess the similarity of novel agents to TFMPP. First, rats were trained to reliably discriminate between the stimulus properties of intraperitoneally administered 1.0 mg/kg TFMPP and its vehicle. Following the acquisition of this discrimination, administration of various doses of TFMPP produced a typical dose-response relationship with an ED50 of 0.27 mg/kg. Rats were subsequently tested with another 5-HT1B specific agonist 1-(3-chlorophenyl)piperazine (mCPP) and a 5-HT releasing agent norfenfluramine and both produced TFMPP-like discriminative responding in a dose-dependent manner. In contrast, the 5-HT2 agonist 4-iodo-1-(2,5-dimethoxyphenyl)-2-aminopropane (DOI) did not generalize from TFMPP. Other drugs, previously trained in other rats and shown to generalize to TFMPP, viz., ethanol, tetrahydro-beta-carboline (THBC) and 3,4-methylenedioxymethamphetamine (MDMA) did not produce TFMPP-like responding. These results provide further evidence for the 5-HT1B receptor acting as the site for the discriminative effects of TFMPP. In addition, the transfer of discrimination between TFMPP and either ethanol, THBC or MDMA appears to be asymmetrical. Reasons for this one-way generalization are suggested.
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PMID:Use of TFMPP stimulus properties as a model of 5-HT1B receptor activation. 325 60

The ethanol-like discriminative stimulus effects of N-methyl-D-aspartate (NMDA) antagonists that act at the NMDA recognition site [(D)-4-(3-phosphonoprop-2-enyl)piperazine-2-carboxylic acid (CPPene) and cis-4-phosphonomethyl-2-piperidine carboxylic acid] or within the NMDA associated cation channel [phencyclidine (PCP) and dizocilpine] were evaluated in rats trained to discriminate ethanol or PCP from vehicle in a two-lever discrimination procedure. Three groups of rats were trained to discriminate 1.0, 1.5 or 2.0 g/kg of ethanol from water and one group was trained to discriminate 1.5 mg/kg of PCP from saline. In the ethanol-trained groups, both PCP (1.0-5.6 mg/kg; i.p.) and dizocilpine (0.03-0.3 mg/kg; i.p.) completely substituted for ethanol in every rat tested, although the dizocilpine resulted in only partial substitution in rats trained to discriminate 1.0 g/kg of ethanol. As the training dose of ethanol increased, the potency of PCP and dizocilpine to substitute for ethanol increased. In contrast, CPPene (1-17 mg/kg; i.p.) and cis-4-phosphonomethyl-2-piperidine carboxylic acid (5.6-17 mg/kg; i.p.) resulted in partial substitution for ethanol, with lower amounts of ethanol-appropriate responding as the training dose of ethanol increased. These data indicate that uncompetitive antagonism of NMDA neurotransmission at sites within the cation channel produce discriminative stimulus effects that are similar to those of ethanol, particularly to higher ethanol doses. Neither ethanol (0.5-1.5 g/kg; i.p.) nor CPPene (5.6 and 10 mg/kg) completely substituted for the discriminative effects of PCP. The asymmetrical generalizations between ethanol and PCP are discussed in terms of the mixed discriminative effects of ethanol.
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PMID:Discriminative stimulus effects of ethanol: effect of training dose on the substitution of N-methyl-D-aspartate antagonists. 845 Apr 61