Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “SYMPATHOMIMETICS”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 289 records · Page 16Linked to original sources
PubMed1998

Evaluation of intrinsic sympathomimetic activity of bucindolol and carvedilol in rat heart.

Many beta-adrenoceptor antagonists are weak partial agonists, possessing significant intrinsic sympathomimetic activity (ISA). Under certain conditions, ISA may be deleterious through stimulation of beta 1- and/or beta 2-adrenoceptors in the heart. Drugs with ISA are particularly problematic in the treatment of congestive heart failure since agents that activate cardiac beta-adrenoceptors, such as xamoterol, have been associated with increases in the incidence of arrhythmia and mortality. Carvedilol was recently approved for the treatment of congestive heart failure, and bucindolol is currently in large clinical trials for this indication. In the present study, the ISA of bucindolol and carvedilol was evaluated in a standard model used to investigate ISA, the pithed rat. Both compounds produced dose-dependent inhibition of the positive-chronotropic effects of the non-selective beta-adrenoceptor agonist, isoproterenol, confirming that these drugs are beta-adrenoceptor antagonists. However, cumulative administration of bucindolol (10-1,000 micrograms/kg i.v.) in the pithed rat produced a significant dose-related increase in heart rate. The maximal increase in heart rate produced by bucindolol was 44% of that obtained with isoproterenol (90 +/- 6vs. 205 +/- 11 bpm, respectively). In marked contrast, cumulative administration of carvedilol (10-1,000 micrograms/kg i.v.) had no significant effect on resting heart rate in the pithed rat. The maximal increase in heart rate elicited by bucindolol (1,000 micrograms/kg i.v.) was inhibited by treatment with the competitive beta-adrenoceptor antagonist, propranolol (99 +/- 8.7 vs. 26 +/- 2.6 bpm), confirming that the ISA observed with bucindolol was mediated through stimulation of myocardial beta-adrenoceptors. Carvedilol, which had no ISA, antagonized the ISA of bucindolol, and was as effective as propranolol in blocking the ISA of bucindolol (99 +/- 8.7 vs. 27 +/- 2.3 bpm). In summary, bucindolol and carvedilol are both potent beta-adrenoceptor antagonists in the pithed rat: however, only bucindolol possesses beta-adrenoceptor-mediated ISA.

Adrenergic beta-Antagonists↗
PubMed1977

Influence of some sympathomimetic amines on the experimental gastric ulcers in rats.

In reserpine-induced ulcers in rats, the centrally acting sympathomimetic ámines (amphetamine, mephentermine and ephedrine) produced a significant protection. Only amphetamine had a beneficial effect in restraint ulcers. Tyramine, a preponderant peripherally acting sympathominetic amine, was inefficient in both experimental models. It is suggested that the protective activity is due to the influence of these amines on the adrenergic structures, mainly at central level.

Amphetamine↗
PubMed1986

Effects of noncatechol sympathomimetics on glucose output by hepatocytes from normal and dexamethasone-treated rats.

Isolated hepatocytes from collagenase-perfused rat livers were used to study the hyperglycemic potential of various noncatechol sympathomimetics (NCSPM) commonly found in commercially available cough/cold preparations. The effect of various concentrations of ephedrine, pseudoephedrine, and phenylpropanolamine on glucose output were compared in dexamethasone- or saline-pretreated rats. The NCSPM produced minimal or no glucose output at most of the concentrations tested in hepatocytes from normal saline pretreated rats. However, these same compounds were able to stimulate a significant increase in glucose output from hepatocytes pretreated with dexamethasone. The results indicate that corticosteroids can enhance the glycemic potential of characteristically weak, indirectly acting NCSPM.

Animals↗
PubMed1987

Some aspects of the enzymic inactivation of sympathomimetic amines.

This review seeks to discuss the possible importance of monoamine oxidase (MAO) and semicarbazide-sensitive amine oxidase (SSAO) in terminating the effects of released sympathetic transmitters and in the inactivation of endogenous or administered sympathomimetic amines with particular reference to some aspects of the cardiovascular system. Use of in vitro preparations of blood vessels and of other smooth muscles, such as vas deferens and anococcygeus, has thrown light on possible roles for these deaminating enzymes, even in the inactivation of noradrenaline, while the new reversible inhibitors of MAO-A show promise as antidepressants with a reduced risk of hypertensive crises following the ingestion of tyramine-containing food. However, the role of SSAO in the in inactivation of amines remains an enigma, even though much is now known of its biochemical nature. While the pharmacological responses to amine substrates can be potentiated by inhibition of SSAO, there is a suspicion that it is product rather than substrate that is more important.

Amine Oxidase (Copper-Containing)↗
PubMed1987

Mechanism of action of indirectly acting sympathomimetic amines.

The mode of action of indirectly acting sympathomimetic amines was analysed in the rat vas deferens (preloaded with 3H-(-)-noradrenaline). When monoamine oxidase (MAO), catechol-O-methyltransferase and vesicular uptake were inhibited (i.e., when the concentration of 3H-noradrenaline in the axoplasm was high), all substrates of neuronal uptake induced a carrier-mediated outward transport of 3H-noradrenaline, in strict dependence on the Km for neuronal uptake of the substrate. However, when MAO and vesicular uptake were not inhibited, some of the substrates of neuronal uptake were better releasers of 3H-noradrenaline than others; obviously, when the axoplasmic 3H-noradrenaline concentration is very low (intact vesicular uptake, intact MAO), a 'mobilization' of vesicular 3H-noradrenaline is a prerequisite for substantial release.

Animals↗
PubMed1988

Actions of sympathomimetic amines on the Ca2+ transients and contractions of rabbit myocardium: reciprocal changes in myofibrillar responsiveness to Ca2+ mediated through alpha- and beta-adrenoceptors.

The effects of sympathomimetic amines on Ca2+ transients and isometric contractions were assessed in isolated rabbit papillary muscles in which multiple superficial cells had been microinjected with the calcium-sensitive bioluminescent protein aequorin. In the presence of beta-adrenoceptor blockade, the alpha-receptor agonist phenylephrine increased both the amplitude of the aequorin signals and the force of contraction in a concentration-dependent manner. However, the maximum increase in the aequorin signals was less than 10% of that produced by the beta-receptor agonist isoproterenol, while the maximum increase in force of contraction produced by alpha-stimulation was about 50% of that elicited via beta-adrenoceptors. For a given increase in the force of contraction, stimulation of alpha-adrenoceptors produced much less change in the amplitude of the aequorin signals than did elevation of the extracellular Ca2+ concentration; we interpret this to mean that the positive inotropic effect of alpha-adrenoceptor stimulation is in large part the result of an increase in myofibrillar sensitivity to Ca2+. Stimulation of alpha-adrenoceptors produced little change or a slight decrease in the duration of the aequorin signal and an increase in the duration of contraction, while stimulation of beta-adrenoceptors significantly decreased the time to peak and duration of both the aequorin signals and the contractions. For a given level of inotropic effect, high concentrations of isoproterenol often increased the aequorin signals more than did elevations of Ca2+, which is consistent with other evidence that the cyclic AMP-dependent phosphorylation of troponin I leads to a decrease in myofibrillar Ca2+ sensitivity. However, concentrations of isoproterenol that did not produce evidence of this sort of desensitization also abbreviated the contractions much more than they did the aequorin signals. This suggests that the traditionally accepted mechanisms--a decrease in the Ca2+ affinity of troponin C and an acceleration of Ca2+ uptake by the sarcoplasmic reticulum--may not be sufficient to account for the actions of beta-receptor stimulation on the time course of contraction. In the absence of blocking agents, the naturally occurring catecholamines norepinephrine, epinephrine, and dopamine appear to influence the function of the rabbit papillary muscle through both alpha- and beta-adrenoceptors. Dopamine has a relatively greater effect on alpha-adrenoceptors than the other catecholamines.

Animals↗
PubMedDate not supplied

Intrinsic sympathomimetic activity: physiological reality or marketing phenomenon.

Intrinsic sympathomimetic activity (ISA) describes the partial beta-adrenergic agonist responses elicited by a series of beta-adrenergic antagonists. The dual effect on the beta-adrenergic receptor appears to be related to structural specificity of the drugs allowing competitive binding to the receptor (antagonist activity) and partial interaction at the receptor's activation site (agonist activity). The clinical effects of a beta-adrenergic antagonist with ISA depend on the relative balance of the drug's inherent antagonist and agonist activity and on the degree of underlying sympathetic tone in the patient. Theoretically, the agonist activity may be beneficial in the patient in whom beta-adrenergic antagonists are indicated, but who has concomitant bradycardia and/or mild to moderate congestive heart failure or compromised pulmonary function, or in the patient being withdrawn from beta-adrenergic antagonist therapy. There is positive evidence from clinical trials that in select patient populations a few of these benefits of ISA are afforded without compromise to beta-adrenergic antagonist activity. However, predisposing factors such as acute illness and individual idiosyncrasies may interfere with the manifestations of the agonist effects. Further, maximal response to full beta-adrenergic agonists will be diminished by concurrent therapy with beta-adrenergic antagonists regardless of ISA presence. In summary, ISA does have a physiological basis and increased experience in larger patient populations will help to place it in proper clinical perspective.

Adrenergic beta-Antagonists↗
PubMed1988

Treatment of neurogenic orthostatic hypotension with amezinium metilsulfate, a new indirect sympathomimetic drug.

Amezinium metilsulfate is a new, indirectly acting sympathomimetic drug which exclusively affects postganglionic sympathetic neurons and inhibits both intraneuronal monoamine oxidase and norepinephrine reuptake. We examined the short-term effects of amezinium in five patients with severe neurogenic orthostatic hypotension. Single-dose administration of amezinium (10 mg) raised both the supine and sitting mean blood pressures by 15 to 45 mm Hg for 8 hours, with a slight increase in the plasma norepinephrine level. Repeated administration of amezinium (10 to 40 mg/d) produced an increase in sitting blood pressure in three patients and improvement of the orthostatic symptoms in all patients without remarkable recumbent hypertension. The heart rate was increased in two patients. The results indicate that amezinium is of therapeutic value for the treatment of neurogenic orthostatic hypotension. The adrenergic effect of amezinium on the blood pressure and heart rate apparently was related to a slight increase in endogenous norepinephrine in the presence of alpha- and beta-adrenoreceptor supersensitivity.

Adult↗
PubMed2001

Separation of sympathomimetic amines of abuse and related compounds by micellar electrokinetic chromatography.

Separation of twelve sympathomimetic amines and related compounds by micellar electrokinetic chromatography (MEKC) with UV absorbance detection is described. These amines were well separated within 25 min using 50 mM sodium tetraborate solution containing 15 mM sodium dodecylsulfate (SDS) of pH 9.3 as a running solution and detected at 210 nm. MEKC was performed with an applied voltage of 13 kV at 25 degrees C using a fused-silica capillary (50 cm x 75 mm i.d.) with effective length of 37.5 cm. The detection limits of these compounds were in the range from 4 to 97 fmol/injection at a signal-to-noise ratio (S/N) of 3. The reproducibility of the method expressed as relative standard deviation (RSD) for within-day (n=6) and between-day (n=5) assays was less than 4.8 and 8.8%, respectively. The proposed method could be applied to the determination of an anorectic drug, phentermine, in Chinese tea with a detection limit of 99 microg/g (105 fmol/injection, S/N=3).

Calibration↗
PubMed1990

[Pharmacological studies of celiprolol: I. Beta-blocking effect, intrinsic sympathomimetic activity, vasodilating and hypotensive effects].

The beta-blocking effect, intrinsic sympathomimetic activity (ISA), and vasodilating and hypotensive effects of celiprolol were tested. 1. Celiprolol competitively antagonized the isoproterenol-induced positive chronotropic and inotropic effects in guinea pig right atrial and papillary muscles and isoproterenol-induced guinea pig tracheal relaxation with pA2 values of 8.03, 7.98 and 6.43, respectively. 2. In dogs, isoproterenol-induced increases in cardiac contractility and heart rate were markedly inhibited by celiprolol (83.1 and 84.8%, respectively), while isoproterenol-induced hypotension was suppressed only by 16.8%. 3. Celiprolol increased the beating rate of the right atrium and relaxed the trachea isolated from normal and reserpinized guinea pigs. Celiprolol also potentiated the contractility of the left atrium isolated from reserpinized animals. These effects of celiprolol were antagonized by propranolol. 4. Celiprolol concentration-dependently relaxed rat femoral arteries contracted by methoxamine. The concentration-relaxation curve was shifted to the right by pretreatment with propranolol. 5. Orally administered celiprolol produced long lasting hypotension in conscious SHR without any heart rate change. 6. These results indicate that celiprolol is a highly cardioselective beta-blocker with a significant ISA, which contributes to its vasodilatory and hypotensive effects.

Adrenergic beta-Antagonists↗
PubMed1979

Failure of dibutyryl and 8-bromo-cyclic GMP to mimic the antagonistic action of carbachol on the positive inotropic effects of sympathomimetic amines in the canine isolated ventricular myocardium.

Effects of carbachol, dbcGMP and 8-bromo-cyclic GMP on the positive inotropic actions of sympathomimetic amines and dbcAMP were studied on the canine isolated right ventricular myocardium. Carbachol alone did not substantially change the developed tension of the muscle, but did markedly shift the dose response curve for isoprenaline on the developed tension to the right and depressed the maximal response to the drug in a concentration dependent manner. The positive inotropic action of phenylephrine was affected by carbachol in the same manner as that of isoprenaline. DbcGMP in concentrations of 10(-3) M and higher produced a significant increase in the developed tension. The positive inotropic action of dbcGMP was partly inhibited by a beta-adrenoceptor blocking agent, pindolol. In the presence of dbcGMP, isoprenaline produced an action similar to that seen in the control experiment, but this action was not maintained on such a steady state level as in the control. This rapid decline of the effect of isoprenaline in the presence of dbcGMP was prevented by adding ascorbic acid to the organ bath. The positive inotropic actions of phenylephrine and of dbcAMP were not substantially affected by dbcGMP. 8-Bromo-cyclic GMP in a concentration of 10(-4) M did not change either the basal developed tension or the positive inotropic actions of noradrenaline and of isoprenaline. The present results indicate that these cyclic GMP derivatives are not able to mimic the antagonistic action of cholinergic stimulation on the positive inotropic action of adrenergic stimulation on the positive inotropic action of adrenergic stimulation on the canine ventricular myocardium.

Animals↗
PubMed2004

Characterization of intrinsic sympathomimetic activity of carteolol in rat cardiovascular preparations.

We evaluated in vitro, in myocardial and vascular preparations isolated from reserpine-treated rats, the intrinsic sympathomimetic activity (ISA) of carteolol, a beta(1)/beta(2)-adrenoceptor blocking agent used in cardiovascular and non-cardiovascular diseases. In spontaneously beating atria, carteolol, at low concentrations (0.01 and 0.1 microM), antagonized the positive inotropic effect of isoprenaline, whereas at higher concentrations (1 microM to 1 mM), it caused an increase in the force of contraction (EC(50): 4.6 +/- 0.1 microM, E(max): 17.1 +/- 1.1%, with respect to the maximum isoprenaline response) and a slight increase (7.8 +/- 1.9% over basal values) in the heart rate. The positive inotropic effect of carteolol was abolished by concentrations of propranolol or timolol (10 microM) much higher than those blocking isoprenaline effects in the same preparations. A similar positive inotropic effect was also observed in electrically driven left atrium and in Langendorff perfused hearts. Functional and biochemical evidences supported the involvement of cAMP in the cardiac action of carteolol. In peripheral arteries (femoral and tail) pre-contracted with phenylephrine, carteolol exerted ISA-related relaxing effects, independent of the presence of endothelium and sensitive to high concentrations (10 microM) of conventional beta-blockers. On the basis of these results, we propose to categorize carteolol as a non-conventional partial agonist of both cardiac and vascular beta-adrenoceptors.

Animals↗
PubMed1995

The role of renal dopamine in the reduction of high blood pressure by beta 1-selective beta-blocker with intrinsic sympathomimetic activity in spontaneously hypertensive rats.

The present experiments were undertaken to clarify the difference of renal dopamine production from beta 1-selective beta-blocker with and without intrinsic sympathomimetic activity (ISA). Either beta-blocker with ISA, celiprolol (100 or 300 mg/kg/day; CEL-100 or CEL-300) or beta-blocker without ISA, atenolol (50 mg/kg/day; ATE-50) was administered to the SHR from 19 to 26 weeks. Degrees of lowering blood pressure in CEL-300 SHR and in ATE-50 SHR were similar, but decrease in heart rate was significantly less in CEL-300 SHR than in ATE-50 SHR. Urine output, which was significantly less in control SHR than in control WKY, was significantly greater in CEL-100 SHR and CEL-300 SHR, but not in ATE-50 SHR. Urinary excretions of noradrenaline (u-NA) and dopamine (u-DA) were significantly higher in control SHR than in control WKY and a comparable u-DA/u-NA ratio was found in these two groups. U-DA and the ratio of u-DA/u-NA were significantly elevated in CEL-100 SHR and CEL-300 SHR, but not in ATE-50 SHR. There was a significant positive correlation between u-DA/u-NA ratio and urine output and a significant negative correlation between the ratio of u-DA/u-NA and change of blood pressure in control SHR, CEL-100 SHR and CEL-300 SHR. These results suggest that an enhancement of renal dopamine production by ISA (beta 2 stimulation) of beta 1-selective beta-blocker may contribute, at least in part, to the antihypertensive effect of this drug.

Adrenergic beta-1 Receptor Antagonists↗
PubMed1981

Dopamine receptors do not influence beta2-sympathomimetic-mediated inhibition of gastric acid secretion in the dog.

The effect of dopamine blockade by haloperidol and metoclopramide on beta2-adrenergic-induced changes of acid secretion and pulse rate was studied in conscious gastric fistula dogs. Neither haloperidol (0.15 mg/kg and 0.60 mg/kg) nor metoclopramide (0.25 mg/kg and 1.0 mg/kg), given intravenously, had a significant influence on beta2-adrenergic-induced inhibition of gastric acid secretion or tachycardia. Dopamine blockade had no influence on pentagastrin-stimulated gastric acid secretion, but it increased pulse rate. It is concluded that dopamine receptors are not involved in the inhibiton of acid output or tachycardia induced by beta2-sympathomimetics, and dopamine is probably not a neurotransmitter for these effects.

Adrenergic beta-2 Receptor Agonists↗
PubMed1980

Ocular toxicity in beagle dogs with an experimental fluoromethane-sulfonanilide sympathomimetic agent.

ocular lesions were detected in Beagle dogs receiving high doses of BA6650, an experimental fluoremethane-sulfonanilide sympathomimetic agent, during a preclinical safety evaluation study. The oral dose of BA6650 was increased during the 14-day study from 20 mg/kg twice daily (bid) for days 1-3 to 30 mg/kg bid for days 4-6 and finally to 40 mg/kg bid for days 7-14. Two males and two females received BA6650 while one male and one female were not dosed. Intraocular pressure in the untreated controls fluctuated during the study between 17 and 22 mmHg. Intraocular pressure decreased in 3 of 4 BA6650 treated dogs from an initial mean value of 17 to a final mean value of 8 mmHg. Ocular lesions consisting of conjunctival hyperemia, corneal opacities, epiphora, mydriasis followed by miosis, corneal herniation, hypopyon, ptosis, and anterior synechia developed in three of the animals.

Animals↗
PubMed1986

Sympathomimetic protein secretion by young and aged lacrimal gland.

The diminished basal tear flow in aged individuals is associated with lymphocytic infiltrations and atrophy of the lacrimal ducts and acini. We have investigated the age-related physiological changes to sympathomimetic stimulation of lacrimal tissue from F344 rats to determine if the responses are uniformly diminished as would be expected by glandular atrophy. The quantitative and temporal pattern of protein and peroxidase secretion by lacrimal gland fragments from young (4 month) and aged (24 month) F344 male rats was examined in a perifusion system. Upon stimulation of tissue from young animals with 0.01 mM phenylephrine for 40 min, secretion above baseline levels of protein was 570.8 micrograms/g tissue and of peroxidase was 45.2 delta A X min-1/g tissue. The response of the aged tissue to phenylephrine was not significantly different from that of the young tissue. beta-adrenergic stimulation by isoproterenol (0.01 mM) evoked only a modest secretion of protein and no consistently measurable peroxidase from young tissue. IBMX alone and in combination with isoproterenol (0.1 mM and 0.01 mM respectively) evoked a large secretion of protein, 1345.7 micrograms/g tissue, and a modest secretion of peroxidase, 9.5 delta A X min-1/g tissue by young tissue. The aged tissue, upon stimulation with the combination of IBMX and isoproterenol, secreted significantly less protein and peroxidase than the young tissue. In separate experiments, the production of cAMP was measured. In young tissue, isoproterenol did not cause a measurable increase of intracellular cAMP. IBMX caused a 2-3 fold increase in cellular cAMP which was not increased further by addition of isoproterenol.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-3-isobutylxanthine↗
PubMedDate not supplied

Relationship between beta adrenoceptor occupancy and receptor down-regulation induced by beta antagonists with intrinsic sympathomimetic activity.

The relationship between the Ki of the B2 adrenoceptor and EC50 values characterizing receptor down-regulation induced by isoproterenol and six beta antagonists classified as having weak to strong intrinsic sympathomimetic activity (ISA) was determined using L6 myoblasts. It was hypothesized that if receptor loss induced by beta antagonists with ISA was mediated through cAMP, EC50 = Ki. EC50/Ki ratios for (-)isoproterenol, (-) and (+) celiprolol were 0.006, 0.01 and 0.08, respectively (p < 0.05); ratios for (-)pindolol and dilevalol were 19 and 9.5, respectively (p < 0.05). EC50/Ki ratios for acebutalol and (-)alprenolol were not significantly different from 1.0. Isoproterenol and dilevalol maximally down-regulated receptor density 89 and 83%, respectively, followed by (+)celiprolol, 54%; (-)celiprolol, 53%; acebutalol, 41%; (-)pindolol, 36% and (-)alprenolol, 31%. Receptor loss was blocked in each case by ICI118,551 or sotalol. A sensitive radioimmunoassay failed to detect increased cAMP accumulation following pretreatment with concentrations of acebutalol, (-)alprenolol, celiprolol and (-)pindolol 100 times their respective Ki values. Isoproterenol and dilevalol stimulated cAMP accumulation 100- and 2-fold over basal, respectively. We conclude that receptor loss induced by beta antagonists with ISA is mediated through the beta 2 adrenoceptor and in at least some cases is cAMP-independent.

Acebutolol↗
PubMed1975

Hepatic potassium movements induced by sympathomimetic amines before and after adrenergic blockade.

The hepatic K+-mobilizing effects of phenylephrine and isoproterenol were studied in dogs equipped with chronic indwelling portal vein catheters. Animals anesthetized with sodium pentobarbital, received intraportal injections of these sympathomimetic amines, alone or in combination, before and after alpha, or beta, or combined adrenergic blockade. Hepatic K+ movements were assessed by measuring systemic arterial and hepatic venous K+ levels. It was concluded that adrenergic blockade exerted no significant influence on the ability of these agents to provoke the initial release and subsequent uptake of K+ by the liver.

Animals↗