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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental pharmacology and physiology 1 (1974), S. 0 
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: SUMMARY 1. The actions and interactions of compounds with phosphodiesterase-in-hibiting activity and of sympathomimetic amines have been studied on contractions of skeletal muscles in chloralose-anaesthetized cats treated with bethanidine and in which the adrenals were excluded from the circulation.2. Compounds with phosphodiesterase-inhibiting activity, ICI 63,197, ICI 58,301, papaverine, theophylline, and dipyridamole, potentiated isoprenaline in its depressant effect on tension and fusion of incomplete tetanic contractions of the slow-contracting soleus muscle, the order of potency being as listed. ICI 63,197 and theophylline also potentiated adrenaline and salbutamol in depressing contractions.3. ICI 63,197 potentiated isoprenaline in its enhancing effect on tension and degree of fusion of incomplete tetanic contractions of the fast-contracting tibialis anterior and flexor digitorum longus muscles.4. The results are compatible with the hypothesis that the effects of sympathomimetic amines on muscle contractility are mediated by cyclic adenosine-3',5'-monophosphate, although this nucleotide and its dibutyryl analogue, injected intra-arterially, were themselves without any consistent effect.5. High doses of ICI 63,197, ICI 58,301, papaverine and dipyridamole, themselves produced isoprenaline-like effects on the soleus muscle. These effects were partially antagonized by (±)-propranolol, (+)-propranolol, or sotalol. The (+)-isomer of propranolol was only about ten times less potent than racemic propranolol in this respect. This antagonistic action of propranolol and sotalol appeared to be independent of β-adrenoceptor blockade.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental pharmacology and physiology 1 (1974), S. 0 
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: SUMMARY 1. Dantrolene depresses the tension of directly or indirectly elicited twitches and tetaní of the tíbíalís anteríor and soleus muscles of cats under chloralose anaesthesia, without affecting the gross muscle action potentials.2. The decrease in twitch tension is associated with slowed rates of rise of tension and of relaxation, but there is no change in the time to peak tension. The decrease in maximal tetanic tension is associated with a slowed rate of rise of tension, but there is no change in the rate of relaxation. It is concluded that dantrolene decreases the intensity of the active state, possibly by impairing the release of Ca2+ from the sarcoplasmic reticulum.3. The soleus muscle is slightly more resistant than the tibialis anterior muscle to the action of dantrolene, and maximal tetani of both muscles are much more resistant than twitches.4. Adrenaline, theophylline and quazodine produce effects on the dantrolene-depressed twitches that are proportionately the same as those produced on the control twitches; there is no evidence of a specific antagonistic effect of any of these drugs.5. Tetanic stimulation of the tibialis anterior muscle but not the soleus muscle causes a temporary relief of the twitch depression produced by dantrolene.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental pharmacology and physiology 10 (1983), S. 0 
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. Cyclic AMP and cyclic GMP levels were determined in bovine splenic nerve segments in the absence and presence of (±) - isoprenaline, (-)-phenylephrine, clonidine and ICI 63 197 (a phosphodiesterase inhibitor). The chosen concentrations of adrenoceptor agonists were those which are known to affect stimulation-induced overflow of noradrenaline from nerve terminals.2. The mean levels of cyclic AMP ranged from 229 to 555 pmol/g of microwave irradiated tissue. Mean cyclic GMP levels ranged from 27.9 to 42.2 pmol/g.3.Isoprenaline enhanced cyclic AMP levels but did not affect cyclic GMP levels. The effect was blocked with (±)-propranolol. ICI 63 197 increased cyclic AMP levels but did not change cyclic GMP. Phenylephrine and clonidine caused no consistent changes in cyclic AMP or cyclic GMP levels or in the concentration ratio between these two nucleotides.4.The results support the involvement of cyclic AMP in the enhancing effect of β-adrenoceptor agonists and phosphodiesterase inhibitors on stimulation-induced release of noradrenaline from sympathetic nerves.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental pharmacology and physiology 5 (1978), S. 0 
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental pharmacology and physiology 5 (1978), S. 0 
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. Levodopa, dopamine, noradrenaline and adrenaline (in increasing order of potency) depressed the tension and degree of fusion of incomplete tetanic contractions of the slow-contracting soleus muscle in chloralose-anaesthetized cats.2. The effects of all compounds were antagonized by propranolol (50-20 μg/kg), but not practolol (1.0-5.0 mg/kg). This indicates that effects are mediated by β2-adrenoceptor stimulation.3. The effect of levodopa, but not of the catecholamines, was antagonized by prior administration of the dopa decarboxylase inhibitor benserazide. This indicates that levodopa itself is inactive, whereas its decarboxylated metabolites are active.4. The depressant action of β-adrenoceptor agonists on incomplete tetanic contractions of the cat soleus muscle, which are exerted directly on the muscle fibres, is a model for effects exerted on slow-contracting units of human muscles; the latter effects probably underlie the tremor observed after β-adrenoceptor agonist administration.5. These results therefore suggest that levodopa, via its decarboxylated metabolites, dopamine, noradrenaline and adrenaline, may produce or exacerbate tremor in man. Thus in Parkinsonian patients, any centrally induced relief of tremor that levodopa may produce may be masked by tremorogenic effects of such metabolites exerted in the periphery.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental pharmacology and physiology 8 (1981), S. 0 
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1. Cyclic AMP levels have been determined in the soleus muscles of anaesthetized cats in the absence of drugs, and during depression of incomplete tetanic contractions produced by (-)-isoprenaline, ICI 63,197 (a phosphodiesterase inhibitor) or levodopa.2. Cyclic AMP levels were elevated at the peak of tension depression produced by isoprenaline. Effects of isoprenaline on cyclic AMP and on contractions were dose dependent and statistically significantly related one to the other. Both effects were blocked by propranolol.3. ICI 63,197 and levodopa produced isoprenaline-like effects on contractions but times to peak effect and recovery were longer. Cyclic AMP levels estimated during the depressant action were elevated.4. The results support the involvement of cyclic AMP in the depressant effect of β-adrenoreceptor agonists on slow-contracting mammalian skeletal muscle.
    Type of Medium: Electronic Resource
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