Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1323099 (sympathomimetic)
 2,957 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Papaverine is believed to relax smooth muscle by reducing transmembrane calcium transport and cyclic nucleotide phosphodiesterase activity. The present study characterizes the different relaxing effects of papaverine on isolated muscle strips of rat bladder dome. Compared to histamine, norepinephrine and serotonin, carbachol and high potassium induced the most prominent contractions in rat bladder strips. For this reason both agents were used as stimulants. High-potassium-induced muscle contractions were reduced by a lower concentration of papaverine than carbachol-induced muscle concentrations. Compared to verapamil, papaverine, especially in low concentrations, was less potent on both kinds of induced muscle contractions. These tension responses correspond to a difference in 45Ca uptake, suggesting a nonspecific blocking property of papaverine on transmembrane calcium channels. The beta-sympathomimetic effects of isoprenaline on carbachol-induced contractions were not enhanced by verapamil. In contrast, papaverine increased this tension response of isoprenaline on carbachol-induced contraction. From these results it is possible that part of the papaverine action seems to be related to an intracellular mechanism probably to cAMP.
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PMID:Effects of papaverine on tension and 45Ca-uptake in isolated urinary bladder. 165 18

Dose-dependent responses to L-isoprenaline of spontaneous activity and plateau height in Purkinje fibres can be mimicked closely by the PDE-inhibitor IBMX. Simultaneous applications of sympathomimetic amines and IBMX result in potentiated responses. The results support the hypothesis that cyclic-AMP is the common mediator of positive chronotropic and inotropic effects induced by beta-sympathomimetic amines.
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PMID:The effects of beta-sympathomimetic amines and phosphodiesterase inhibitors on electrophysiological parameters in Purkinje fibres. 615 87

Quantitative structure-activity relationships (QSARs) of different cardiotonic agents are presented. A critical analysis of all QSARs provides a very vivid picture of the mechanisms of varying cardiotonic agents. The cardiotonics can be broadly put into 2 categories: cardiac glycosides and nonglycoside cardiotonics, which include phosphodiesterase of type III (PDE III) inhibitors, sympathomimetic (adrenergic) stimulants, A1-selective adenosine antagonists, Ca2+ channel activators and vasopressin antagonists. For cardiac glycosides, QSARs reveal that the position of carbonyl oxygen in their lactone moiety and shifting of the lactone ring from its original position or its replacement by another group would be crucial for their activity. The carbonyl group or its isostere like CN is indicated to be the sole binding entity and the hydrogen bonding through this group is considered to be the most likely binding force. For nonglycoside cardiotonics that include PDE III inhibitors and A1-selective antagonists, a five-point model has been established for their activity, the salient features of which are: (1) the presence of a strong dipole, (2) an adjacent acidic proton, (3) a methyl-sized lipophilic space, (4) a relatively flat overall topography and (5) a basic or hydrogen-bond acceptor site opposite to the dipole. For Ca2+ channel activators, the importance of steric, electrostatic, lipophilic and hydrogen-bonding properties of molecules is indicated, while for vasopressin antagonists the lipophilic and electronic properties are suggested to be the most important.
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PMID:Quantitative structure-activity relationships of cardiotonic agents. 1112 65