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  • 1
    Electronic Resource
    Electronic Resource
    Structure-activity studies on nifedipine in isolated cardiac muscle (1979)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 310 (1979), S. 69-78 
    Details
    ISSN: 1432-1912
    Keywords: Nifedipine ; Cat papillary muscle ; Inotropic effects ; Structure-activity relationship ; Hansch analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. The effects on contractile activity of 2 series of nifedipine-derivatives were investigated in isolated, isotonically contracting cat papillary muscles. 2. For structure-activity studies the lipophilicity of all compounds was determined by means of reversed phase thin-layer chromatography. 3. Neither the ortho-NO2 group in a series of arylderivatives nor the methyl-esters in a series of esterderivatives were found to be essential for the typical effect of the nifedipine molecule on myocardial contractility. 4. Generally ortho-substituted derivatives induce a greater negative inotropic activity than meta-substituted derivatives. Para-substituted derivatives are the least active compounds. 5. In the group of ester-derivatives activity decreases when lipophilicity and/or volume of the substituent increases. 6. The quantitative analysis (Hansch analysis) revealed significant correlations between the negative inotropic effect and steric substituent parameters. Best correlations were obtained with: i) the minimum width, B 1 (ortho-substituted derivatives); ii) the van der Waals volume, V w (ester-substituted derivatives); iii) the experimentally or theoretically determined lipophilicity, R M or π, respectively (ester-derivatives). 7. It is concluded that-within a group of nifedipine derivatives-the negative inotropic effect depends mainly on steric and on lipophilic and/or steric substituent properties for aryl- and ester-derivatives, respectively. Electronic influences are not important for the biological activity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00499876
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  • 2
    Electronic Resource
    Electronic Resource
    The effects of nifedipine on contraction and monophasic action potential of isolated cat myocardium (1977)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 301 (1977), S. 29-37 
    Details
    ISSN: 1432-1912
    Keywords: Nifedipine ; Mammalian cardiac muscle ; Amplitude-frequency relationship ; Staircase phenomena ; Transmembrane action potential ; SA-nodal rate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. The effects of nifedipine (3×10−11–3×10−6 M) on contractile activity and transmembrane action potential (AP) were studied in isotonically contracting cat papillary muscles and in isolated SA-nodes. 2. Nifedipine (3×10−8–3×10−6 M) reduces the amplitudes of contraction. The effect is nearly independent of stimulation rate such that at 6/min the ED50 amounts to 6.1×10−7 M as compared to 5.1×10−7 M at 60/min. This negative inotropic action can be nearly completely antagonized by raising [Ca2+] o . 3. Nifedipine induces short-lasting negative stair-cases developing upon step increases of stimulation rate. Raising [Ca2+] o does not counteract this effect. 4. Nifedipine exerts a dual action on the amplitudeinterval relationship for simple test contractions elicited after a variable period of rest and preceding conditioning stimulation: (i) a flattening of the initial part of the “restitution” curve and (ii) a depression of the steady-state level reached after 2–10 s of rest. Raising [Ca2+] o elevates the steady state to control level but does not reestablish the initial slope of the curve. 5. Nifedipine, while leaving resting potential, maximum rate of depolarization and overshoot unaffected, tends to abbreviate the AP duration. Since this effect is more pronounced at lower frequencies, the usual prolongation of the AP occurring at low stimulation rates is inhibited. The AP plateau is depressed, but this effect seems to be stronger at higher stimulation rates. 6. In isolated SA nodes nifedipine (3×10−7–1×10−6 M) decreases discharge rate by reducing both the rate of the slow diastolic depolarization and the maximal diastolic potential until intranodal conduction blocks occur. 7. It is concluded that the negative inotropic action of nifedipine results mainly from diminished transmembrane Ca supply, with a slight action on internal sites of cardiac e.-c. coupling.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00501261
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  • 3
    Electronic Resource
    Electronic Resource
    Ueber die Monochlorderivate des o-Xylols und ihre Beziehungen zu den Chlor-o-toluylsäuren (1893)
    Weinheim : Wiley-Blackwell
    Liebigs Annalen 274 (1893), S. 304-311 
    Details
    ISSN: 0075-4617
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jlac.18932740304
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  • 4
    Electronic Resource
    Electronic Resource
    Über die Aufspaltung des Pyridins (1911)
    New York, NY : Wiley-Blackwell
    Journal für Praktische Chemie/Chemiker-Zeitung 83 (1911), S. 325-328 
    Details
    ISSN: 0021-8383
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/prac.19110830124
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