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Query: UMLS:C1323099 (sympathomimetic)
 2,957 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A series of new sympathomimetic amines containing an 8-hydroxycarbostyril moiety was synthesized. These compounds probably exist as resonance hybrids having two acidic hydrogen atoms in locations approximating to those of the hydroxyl groups of catechol-containing adrenergic agents. In an in vitro test, many of these compounds showed potent activity for relaxation of guinea pig tracheal smooth muscle. One of the compounds was 24 000 times more potent than isoproterenol. Their actions on cardiac muscle were also examined in vitro by measuring increase in the beating rate of the right atria of guinea pigs. Several of the compounds appeared to be beta-selective. Some of the compounds seem suitable for use as bronchodilators. The structure-activity relationships of these compounds were discussed in comparison with those of catecholamines.
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PMID:Sympathomimetic amines having a carbostyril nucleus. 1 Apr 41

To elucidate the biochemical mechanism by which the sympathomimetic agent clenbuterol promotes skeletal muscle growth, we have determined the activity of a range of proteolytic enzyme types (acid, neutral and alkaline proteinases and peptidases), together with the levels of soluble and structural proteins (via SDS-polyacrylamide gel electrophoresis) in 5 innervated and denervated muscle types from control and drug-treated rats. No gross change in activity was found for any enzyme type in any muscle (innervated or denervated) following clenbuterol treatment; however, one enzyme, arginyl aminopeptidase, showed a small but consistent decrease in activity in all of the innervated muscles investigated. Similar fractionation profiles were obtained for structural or soluble proteins from corresponding muscle types (innervated or denervated) in control or clenbuterol-treated animals, with the exception of cardiac muscle, which showed a 50% increase in staining intensity of one band (subunit molecular mass 18 kD). We conclude that the anabolic action of clenbuterol in promoting skeletal muscle growth does not occur via downregulation of protease activity, or increase in levels of individual muscle proteins.
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PMID:Effect of clenbuterol on protease activities and protein levels in rat muscle. 156 15

The investigational sympathomimetic amine, ractopamine hydrochloride, has been profiled for adrenergic activity in selected smooth and cardiac muscle preparations. There was no significant interaction of ractopamine with alpha-adrenergic receptors in the rat vas deferens at concentrations up to 10(-5) M. However, ractopamine produced a concentration-dependent increase in the force and rate of contractions of atria isolated from normal and reserpinized guinea-pigs (EC50 = 1 x 10(-7) M). These increases were submaximal compared with isoprenaline (70-85%), suggesting partial agonist activity at the beta 1-receptor site. Ractopamine completely relaxed the KCl-contracted guinea-pig trachea and rat costo-uterine smooth muscle to their resting tensions (EC50 = 3 x 10(-7) and 5.5 x 10(-8) M, respectively), indicative of full beta 2-agonist properties. Propranolol blocked the response of ractopamine in isolated tracheal and atrial tissues (pA2 = 7.70), demonstrating a beta-adrenergic mechanism of activity. Ractopamine also exhibited antagonism of the response of the guinea-pig trachea to the beta-agonist, isoprenaline. Relative to other beta-agonists, ractopamine was 100-fold more potent than the phenethanolamines, salbutamol and ritodrine, at the beta 1-adrenoceptor, and approximately 7- to 11-fold more potent than ritodrine, but only one-sixth to one-tenth as potent as salbutamol at the beta 2-adrenoceptor. Thus, ractopamine possesses significant beta 1- and beta 2-agonist properties. The submaximal stimulation of the force and rate of atrial contractions is indicative of a partial beta 1-agonist, while the maximal relaxation of the tracheal and costo-uterine smooth muscle is characteristic of a full beta 2-agonist.
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PMID:Beta-adrenoceptor profile of ractopamine HCl in isolated smooth and cardiac muscle tissues of rat and guinea-pig. 168 83

Cardiac transplantation is theoretically the optimal final treatment of terminal cardiac failure but the indications, especially in the emergency situation, should be carefully considered. Sympathomimetic agents are of limited use in patients with severe cardiac failure partly because of the down regulation of the myocardial beta-receptors. The phosphodiesterase inhibitors, represented by enoximone, are valuable because of their action on the cardiac muscle (inotropic and lusitropic) and their direct systemic vasodilator effect. Enoximone can be administered by intravenous bolus resulting in a rapid onset of action (peak at 30 minutes) with a prolonged effect due to its hepatic metabolites. The authors' experience in this indication dates over 5 years and over 50 patients were included. A preliminary study in 34 patients with cardiac failure resistant to betamimetic drugs, referred to the intensive care unit for urgent cardiac transplantation, or, in the absence of a donor, circulatory assistance is reported. A Swan Ganz catheter and radial artery canula were inserted for haemodynamic monitoring and enoximone was administered in an intravenous bolus over 15 minutes every 8 hours in addition to sympathomimetic agents. A haemodynamic improvement was observed after the 30th minute in 30 patients. The cardiac index increased from 1.82 to 2.67 l/mn/m2 and the pulmonary capillary pressures decreased from 30.8 to 18.9 mmHg. Systemic arterial resistances fell from 2,170 to 1,520 dynes.s.cm-5. No haemodynamic improvement was observed in 4 patients who were treated by mechanical ventricular assistance. After investigations to detect contra-indications to cardiac transplantation, 12 of the 30 patients remained candidates for cardiac transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Medical strategy in patients awaiting emergency heart transplantation]. 214 25

The myofibrillar calcium sensitivity of mammalian skeletal muscle and cardiac muscle may be increased by myosin light chain kinase (MLCK)-induced myosin phosphorylation5) 13). Here we report increasing calcium responsiveness of frog skeletal muscle fibres (Tibialis anterior, skinned by freeze drying) by MLCK-induced myosin P-light chain phosphorylation and by the non-glycoside, non-sympathomimetic positive inotropic drug pimobendan. Investigation of myosin light chains by two dimensional gel electrophoresis revealed two phosphorylatable P-light chains (LC-2) having the same isoelectric point (5.3 for the unphosphorylated, 5.1 for the phosphorylated form) but different molecular weights (19 and 18 kD, respectively). This pattern of LC-2 is distinct from mammalian skeletal and cardiac muscle (only one phosphorylatable P-light chain in skeletal, two phosphorylatable P-light chains in cardiac muscle with different isoelectric points, but identical molecular weight). The phosphorylation level was about 0.45 mole phosphate/mole P-light chains and could be increased by 16 +/- 3% by the addition of myosin light chain kinase. This procedure increased the isometric tension at pCa 5.5 by 21 +/- 5% while maximum tension (at pCa 4.3) was not affected by MLCK. The new inotropic drug pimobendan (10(-4) M) increased isometric tension at pCa 6 by 48 +/- 4.5%, but maximal tension was not affected. Another positive inotropic drug, sulmazole, has been shown to potentiate the twitch of intact frog Tibialis anterior muscle23) and to increase force of skinned fibres by 21.7 +/- 3.3% at submaximal activation (pCa 6).
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PMID:Myofibrillar calcium sensitivity modulation: influence of light chain phosphorylation and positive inotropic drugs on skinned frog skeletal muscle. 326 85

1 The actions of 4-(2-hydroxy-3-isopropylaminopropoxy) phenyl acetamide (ICI 66082), a new beta-adrenoceptor blocking drug, on the twitch response of the isolated papillary muscle of the rabbit and on dP/dt max and free heart rate of a denervated dog heart preparation, are described.2 ICI 66082 (up to 1 mg/ml) did not produce any depression of the twitch response of the rabbit papillary muscle. ICI 66082 antagonized the action of isoprenaline on this preparation at a concentration of 0.01 mug/ml.3 ICI 66082 (0.5-1.0 mg/kg intravenously) reduced the control value of dP/dt max in four dog preparations by a mean value of 529 mmHg/s (s.e. mean +/- 139 mm Hg/s), with no significant change in free heart rate. Antagonism of the effect of isoprenaline on dP/dt max and on free heart rate was demonstrated with ICI 66082 (0.1 mg/kg).4 ICI 66082 (1.0-1.5 mg/kg) produced no significant changes in dP/dt max or in free heart rate in four dogs pretreated with reserpine. A significant reduction (16% of the control value) in dP/dt max was observed with ICI 66082 at a high dose of 40-50 mg/kg.5 It is concluded that ICI 66082 is a competitive antagonist against the actions of isoprenaline on cardiac muscle, has no negative inotropic action (unless the dose exceeds 40 mg/kg) and lacks intrinsic sympathomimetic activity.
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PMID:The actions of a new beta-adrenoceptor blocking drug, ICI 66082, on the rabbit papillary muscle and on the dog heart. 415 70

1. AH 5158 differs from conventional adrenoceptor blocking drugs in producing competitive blockade of both alpha- and beta-adrenoceptors.2. AH 5158 is 5-18 times less potent than propranolol in blocking beta-adrenoceptors. It resembles propranolol in its non-selective blockade of beta(1)-cardiac and beta(2)-vascular and tracheal adrenoceptors and in its lack of intrinsic sympathomimetic activity.3. AH 5158 is 2-7 times less potent than phentolamine in blocking alpha-adrenoceptors. AH 5158 itself is more active on beta- than alpha-adrenoceptors.4. Blockade of noradrenaline vasopressor responses by AH 5158 in anaesthetized dogs was dose-dependent up to 1 mg/kg but no further blockade was obtained with larger doses of AH 5158. ;Self-limiting' blockade was not observed in dogs pretreated with cocaine, or in untreated dogs if the vasopressor agent was oxymetazoline instead of noradrenaline. A possible cause of ;self-limiting' blockade is discussed.5. In doses higher than those required for either alpha- or beta-adrenoceptor blockade, AH 5158 produced effects on cardiac muscle that are attributable to membrane-stabilizing activity. This was manifested as a negative inotropic action in spinal dogs and in guinea-pig left atrial strips, as a negative chronotropic action in syrosingopine pre-treated dogs, and as an increase in the effective refractory period of guinea-pig left atrial strips. AH 5158 was 3-11 times less potent than propranolol in these tests.6. In open chest dogs AH 5158 resembled propranolol in reducing cardiac output, rate and contractility, effects which are attributable to beta-adrenoceptor blockade. The drug differed from propranolol in decreasing rather than increasing total peripheral resistance and in causing larger decreases in arterial blood pressure at equipotent beta-adrenoceptor blocking doses. These differences are attributable to the alpha-adrenoceptor blocking actions of AH 5158.7. In anaesthetized dogs, intravenously administered AH 5158 antagonized both catecholamine and ouabain-induced arrhythmias. Orally administered AH 5158 lowered systolic arterial pressure in conscious renal hypertensive dogs.8. These results show AH 5158 to possess a novel profile of activity. Possible uses of the drug in cardiovascular disorders such as hypertension, angina pectoris and cardiac arrhythmias are discussed.
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PMID:Pharmacology of AH 5158; a drug which blocks both - and -adrenoceptors. 440 13

The cardiac stimulant actions of nine beta-adrenoceptor blocking agents were examined in kitten papillary muscles and in isolated atria of kittens and guinea pigs to determine to what extent these drugs behaved as classical partial agonists. In many ways the agents do appear to comprise a spectrum of partial agonists with widely differing efficacies. However, in one respect the actions of some of the beta-blockers did not fit into the classical mold. Several beta-blockers were found to exert stimulant effects only in concentrations appreciably higher than those required for substantial beta-adrenoceptor blockade. These observations suggest that more than one type of beta-adrenoceptor may be involved in the production of sympathomimetic effects on cardiac muscle.
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PMID:beta-Adrenoceptor blocking agents as partial agonists in isolated heart muscle: dissociation of stimulation and blockade. 610 93

There is some evidence that partial agonism is an important property of beta-blocking drugs, and this property may be exploited to produce a new range of positive inotropic drugs. With the established beta-adrenoceptor-blocking drugs, the level of partial agonist activity is weak and the dose-response curve for this property is shallow. However, its absence appears to increase the likelihood of inducing bronchospasm and bradycardia, and drugs that lack intrinsic sympathomimetic activity appear more likely to be associated with rebound cardiac arrhythmias on cessation of treatment. The idea of a small level of hormone activity--in this case, catecholamine activity--being necessary to maintain normal cardiac and perhaps bronchial function is not new. Minimal doses of steroids are essential to maintaining the inotropic action of cardiac muscle. There is now enough accumulated evidence to suggest that a minimal degree of beta-adrenoceptor stimulation is also important for normal bronchial and cardiac function, and its absence increases the incidence of bradycardia and the risks of bronchospasm and rebound arrhythmias.
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PMID:Beta-adrenoceptor-blocking drugs: current status and the significance of partial agonist activity. 613 43

1. The beta-adrenoceptor blocking and calcitonin gene-related peptide (CGRP)-releasing properties of capsinolol (N-[4-(2-hydroxy-3 (isopropylamino) propoxy)-3-methoxybenzyl]-nonanamide), derived from nonivamide, were investigated under in vivo and in vitro conditions. 2. Capsinolol (0.1, 0.5, 1.0 mg kg-1, i.v.), as well as (+/-)-propranolol, produced a dose-dependent bradycardia response and a temporary pressor action in urethane-anaesthetized normotensive Wistar rats. These cardiovascular effects were different from the vagus reflex and parasympathetic efferent effects shown by capsaicin (0.1 mg kg-1, i.v.) in the rat. 3. Capsinolol (1.0 mg kg-1) inhibited the tachycardia effects induced by (-)-isoprenaline, but had no blocking effect on the arterial pressor responses induced by (-)-phenylephrine. The findings suggest that capsinolol possesses beta-adrenoceptor blocking activity, but it has no alpha-adrenoceptor blocking activity. 4. In guinea-pig isolated tissues, capsinolol (10(-8) to 10(-6) M) antagonized (-)-isoprenaline-induced positive chronotropic and inotropic effects of the atria and tracheal relaxation responses in a concentration-dependent manner. The parallel shift to the right of the concentration-response curve of (-)-isoprenaline suggests capsinolol is a beta-adrenoceptor competitive antagonist. 5. Capsinolol (10(-5) to 10(-4) M) exhibited a positive cardiotonic effect that was not inhibited by (+/-)-propranolol and reserpine, but was inhibited by capsazepine (10(-6) M) and CGRP8-37 (10(-6) M). This effect was independent of intrinsic sympathomimetic effects. 6. An immunoassay of released CGRP from guinea-pig isolated perfused heart indicated that capsinolol increases the release of CGRP and thus produces positive cardiotonic effects. 7. In conclusion, capsinolol is a non-selective beta-adrenoceptor antagonist with capsaicin-like cardiotonic properties unrelated to traditional intrinsic sympathomimetic effects. It is suggested that capsinolol causes CGRP release from cardiac sensory neurones via a non-adrenergic mechanism and then activates CGRP receptors on cardiac muscle.
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PMID:Capsinolol: the first beta-adrenoceptor blocker with an associated calcitonin gene-related peptide releasing activity in the heart. 887 50


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