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  • 1
    Electronic Resource
    Electronic Resource
    The influence of the intrinsic sympathomimetic activity of β-adrenoceptor antagonists on haemodynamic effects in anaesthetized dogs (1979)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental pharmacology and physiology 6 (1979), S. 0 
    Details
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. The effects of propranolol, atenolol (ICI 66,082), practolol and pindolol on heart rate and maximal left ventricular dp/dt, atrioventricular conduction time, mean aortic flow and diastolic blood pressure during cardiac pacing were investigated over a wide dose range (0.025-4.0 mg/kg, i.v.) in dogs anaesthetized with pentobarbitone.2. Propranolol and atenolol produced similar reductions in haemodynamic parameters. Propranolol had no further effect in dogs pretreated with atenolol.3. Practolol tended to cause smaller reductions in the haemodynamic parameters than either propranolol or atenolol. Subsequent administration of propranolol still had some depressant activity.4. Pindolol produced a biphasic response, with depression of cardiac function at the low doses (0.025 and 0.1 mg/kg), but a reversal of effect as the dose was increased.5. It is therefore concluded that, in anaesthetized dogs, the intrinsic activity of practolol and pindolol limits the fall in heart rate, cardiac conduction, aortic flow and maximal dp/dt observed with β-adrenoceptor blockade. With pindolol, however, the influence of intrinsic activity is observed only in high doses related to β-adrenoceptor blockade.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1440-1681.1979.tb00002.x
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    A study of the relationship between cardiac β-adrenoceptor blockade and intrinsic sympathomimetic activity in rats depleted of catecholamines (1979)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental pharmacology and physiology 6 (1979), S. 0 
    Details
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. The intrinsic sympathomimetic acitivity of a range of β-adrenoceptor antagonists and its relationship to β-adrenoceptor blockade was studied in pentobarbitone-anaesthetized, vagotomized rats which had been depleted of catecholamines by pretreatment with syrosingopine.Dichlorisoprenaline, practolol, oxprenolol, pindolol and acebutolol, produced dose-dependent positive chronotropic responses in this preparation.2. The relationship between the dose requirements for this intrinsic sympathomimetic activity and β-adrenoceptor-blocking activity was not the same for all drugs: (i) dichlorisoprenaline and practolol had intrinsic activity at all β-adrenoceptor-blocking doses; and (ii) oxprenolol, pindolol and acebutolol had predominantly β-adrenoceptor blockade at the lower dose levels and agonist activity only became significant at high doses relative to those producing β-adrenoceptor blockade.3. The positive chronotropic response to both practolol and pindolol was observed in rats which had been pithed and was antagonized by propranolol (0.1-3.0 mg/kg, i.v.), indicating that β-adrenoceptors were involved.4. It was concluded that the intrinsic sympathomimetic activity of β-adrenoceptor antagonists was not a simple property as it was described by the relationship between the dose requirements for intrinsic sympathomimetic activity and for β-adrenoceptor blockade as well as the degree of partial agonist activity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1440-1681.1979.tb00001.x
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    An application of receptor models to the analysis of data on β-adrenoceptor blockade (1979)
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental pharmacology and physiology 6 (1979), S. 0 
    Details
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. The classical single receptor competitive occupancy model accurately describes the joint action of an agonist (isoprenaline) and a β-adrenoceptor antagonist (propranolol) or some partial agonists (dichlorisoprenaline, practolol) on the positive chronotropic response in rats which have been depleted of catacholamines.2. The mathematical form of the model suggests that the dissociation constants of classical competitive partial agonists may be assessed using dose ratios by exactly the same method as that currently used for agonist-antagonist interactions, provided that the log dose-response curves are first suitably normalized.3. Close agreement between the theoretical mathematical models and the experimental data can be demonstrated by statistical fitting for certain β-adrenoceptor antagonists (propranolol, dichlorisoprenaline, practolol).4. The model fails to describe the behaviour of other β-adrenoceptor antagonists (oxprenolol, pindolol). A possible extension of the model to include these drugs is proposed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1440-1681.1979.tb00003.x
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
    Fulltext
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