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At least 19 recordsLinked to original sources
PubMed1981

Developmental changes in the sensitivity of the chick embryo ventricle to beta-adrenergic agonist during adrenergic innervation.

As early as the 4th embryonic day, the ventricle of the chick embryo responded to isoproterenol (Iso) with an increase in the force of contraction; at all ages studied, this positive inotropic effect was accompanied by an increased rate of tension development. There was a transient, 10-fold decrease in the sensitivity (increase in ED50) of the right ventricle to Iso between the 16th and 21st embryonic day. This change in the sensitivity to Iso was not due either to an increased inactivation of Iso by non-neuronal cells or to a change in the thickness of the ventricle. It was found that adrenergic nerves were first capable of altering ventricular contractility on the 16th embryonic day. Whereas they interfered with the function of adrenergic nerves, injections of reserpine or 6-hydroxydopamine had no effect on the subsensitivity to Iso. Furthermore, these agents did not affect the normal developmental changes in heart weight. We conclude that the local release of transmitter from adrenergic nerves does not cause the transient subsensitivity of the ventricle of the chick embryo to beta-adrenergic agonists.

Adrenergic beta-Agonists↗
PubMed2001

Alpha2 adrenergic agonists for the management of opioid withdrawal.

BACKGROUND: Withdrawal (detoxification) is necessary prior to drug-free treatment. It may also represent the end point of long-term treatment such as methadone maintenance. The availability of managed withdrawal is essential to an effective treatment system. OBJECTIVES: To assess the effectiveness of interventions involving the use of alpha2 adrenergic agonists (clonidine, lofexidine, guanfacine, guanabenz acetate) to manage the acute phase of opioid withdrawal. SEARCH STRATEGY: Multiple electronic databases were systematically searched. Reference lists of retrieved studies, reviews and conference abstracts were handsearched and relevant pharmaceutical companies contacted. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials that compared alpha2 adrenergic agonists with another form of treatment (or placebo) to modify the signs and symptoms of withdrawal in participants who were primarily opioid dependent. DATA COLLECTION AND ANALYSIS: One reviewer assessed studies for inclusion and undertook data extraction. Inclusion decisions and the overall process were confirmed by consultation between all four reviewers. MAIN RESULTS: Twenty-four studies, involving 1956 participants, were included. Nineteen were randomised controlled trials; in two allocation was by participant choice, one used alternate allocation and in two the method of allocation was unclear. Ten studies compared a treatment regime based on an alpha2 adrenergic agonist with one based on reducing doses of methadone. Diversity in study design, assessment and reporting of outcomes limited the extent of quantitative analysis. From the comparison of alpha2 adrenergic agonist regimes with reducing doses of methadone, withdrawal intensity is similar to, or marginally greater with alpha2 adrenergic agonists, but signs and symptoms of withdrawal occur and resolve earlier in treatment. Participants stay in treatment longer with methadone. The likelihood of completing withdrawal is similar, or slightly less, with clonidine or lofexidine. Clonidine is associated with more adverse effects (low blood pressure, dizziness, dry mouth, lack of energy) than reducing doses of methadone. Lofexidine does not reduce blood pressure to the same extent as clonidine, but is otherwise similar to clonidine. REVIEWER'S CONCLUSIONS: Treatment regimes based on the alpha2 adrenergic agonists clonidine and lofexidine, and those based on reducing doses of methadone over a period of around 10 days, have similar efficacy in the management of withdrawal from heroin or methadone. Participants stay in treatment longer with methadone regimes and experience less adverse effects. The lower incidence of hypotension makes lofexidine more suited to use in outpatient settings than lofexidine. There are insufficient data available to support a conclusion on the efficacy of guanfacine.

Acute Disease↗
PubMed1981

Inhibition of the lipolytic action of beta-adrenergic agonists in human adipocytes by alpha-adrenergic agonists.

The aim of this study was to define the role of the alpha-adrenergic receptor in the regulation of lipolysis by human adipocytes. Glycerol production by isolated human adipocytes was stimulated by the pure beta-adrenergic agonist isoproterenol in a dose-dependent fashion. This stimulation of lipolysis was inhibited by the alpha-adrenergic agonists methoxamine, phenylephrine, and clonidine. Epinephrine-stimulated lipolysis was potentiated by the alpha-adrenergic antagonists, dihydroergocryptine, phentolamine, phenoxybenzamine, and yohimbine. Whereas the attenuation of beta-adrenergic agonist-stimulated lipolysis by alpha-adrenergic agonists was reversed completely by the alpha 2-adrenergic antagonist yohimbine, the alpha 1-antagonist prazosin did not reverse such attenuation. It is concluded that alpha-adrenergic agonists act as antilipolytic agents in human adipocytes and that this action may result from the interaction of these compounds with a population of alpha 2-adrenergic receptors.

Adipose Tissue↗
PubMed1988

Alpha-adrenergic agonists stimulate neonatal glucose production less than beta-adrenergic agonists in the lamb.

Epinephrine, a catecholamine with both alpha (alpha)- and beta (beta)-adrenergic agonist effects, may produce clinical hyperglycemia in the adult by increasing glucose production and decreasing glucose clearance. However, the relative contribution of alpha v beta adrenergic agonists in control of neonatal glucose kinetics has not been defined. Twenty-three term lambs (weighing 4.4 +/- 0.2 kg, mean +/- SEM, and aged 3.8 +/- 0.4 days) were infused with 0.9% NaCl at 0.6 mL.kg-1 min-1 + 100 microCi/kg D[6-3H]-glucose by prime plus constant infusion for 210 minutes. Ra (rate of production) was measured during infusion of variable doses of epinephrine with or without variable doses of propranolol, a competitive beta-adrenergic antagonist to isolate the alpha-adrenergic agonist effects. All basal kinetic data were comparable. Under conditions of epinephrine infusion, the plasma glucose concentration increased from 95 +/- 10 mg/dL to 129 +/- 18 mg/dL (50 ng.kg-1 min-1 epinephrine; P less than .0001) and from 85 +/- 6 mg/dL to 253 +/- 8 mg/dL (500 ng.kg-1 min-1 epinephrine; P less than .00001) compared with controls (96 +/- 7 mg/dL to 95 +/- 8 mg/dL). When epinephrine and propranolol were infused simultaneously, plasma glucose concentration increased from 95 +/- 10 mg/dL to 122 +/- 12 mg/dL (50 ng.kg-1 min-1 epinephrine + 1.1 micrograms.kg-1 min-1; P less than .0001) and from 78 +/- 9 mg/dL to 134 +/- 12 mg/dL (500 ng.kg-1 min-1 epinephrine + 11 micrograms.kg-1 min-1; P less than .0001) compared with controls (no epinephrine, no propranolol).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗
PubMed1984

Influence of fasting on lipolytic response to adrenergic agonists and on adrenergic receptors in subcutaneous adipocytes.

The influence of 1 week's total fasting on the lipolytic effect of adrenergic agonists and on the binding of adrenergic antagonists was examined in isolated adipocytes of subcutaneous specimens removed from the hypogastric and the femoral sites in seventeen obese women. In the femoral adipocytes the lipolytic sensitivity to isopropyl noradrenaline decreased 30-fold (P less than 0.01) during fasting. The specific binding of the radioligands (-)-[3H]-dihydroalprenolol and (-)-[125I]-cyanopindolol decreased significantly during fasting, essentially owing to a reduction in the receptor density. In adipocytes from the hypogastric region no such changes were found. For both tissue regions fasting induced a right-ward shift in the dose-response curve for the inhibitory effect of the alpha 2 agonist, clonidine, on theophylline-induced lipolysis, corresponding to a 10-fold decrease in sensitivity. There was also a significant decrease of about 20% in the alpha 2-adrenoceptor density, as estimated with the radioligand [3H]-yohimbine. The results suggest that the regulation of the lipid mobilization in man by the sympathetic nervous system during fasting occurs not only through an increase in the level of circulating noradrenaline but also through changes in the adrenergic receptor density of the adipocytes.

Adipose Tissue↗
PubMed1995

Beta adrenergic agonists.

Beta adrenergic agonists are the most widely used agents in the management of bronchospasm as a result of their rapid onset of action and predictable efficacy. Administration of these agents by inhalation provides several advantages, including rapid effect, decreased adverse effects, and fewer drug interactions. The newer agents have greater beta-2 selectivity, which contributes to improved tolerance of these agents. Tremor is usually the dose-limiting side effect for the beta-2 selective agents. Other adverse effects include tachycardia, increased blood pressure, headache, anxiety, abnormal glucose metabolism, and hypokalemia. Controversy surrounding the use of beta adrenergic agonists includes reports of an increased mortality rate with increased use of these agents. Current information is inconclusive and should not limit the use of these agents in the management of acute bronchospasm. The significance of tolerance with prolonged administration is also an unresolved issue.

Acute Disease↗
PubMed1998

Anti-obesity effects of selective agonists to the beta 3-adrenergic receptor in dogs. II. Recruitment of thermogenic brown adipocytes and reduction of adiposity after chronic treatment with a beta 3-adrenergic agonist.

The aim of this study was to evaluate the effectiveness of beta 3-adrenergic agonists for the treatment and prevention of obesity in the dog. When a selective beta 3-adrenergic agonist, CL316,243 (0.1 mg/kg), was given orally to adult beagles every day for 5-7 weeks, body weight and girth were decreased compared with control placebo-treated dogs. Gross anatomical examinations revealed no noticeable abnormalities in CL316,243-treated dogs, except an apparent decrease in abdominal fat. Immunohistochemical examination of perirenal adipose tissue showed a remarkable increase in brown adipocytes expressing a thermogenic protein, uncoupling protein (UCP). The increased expression of UCP and its mRNA in CL316,243-treated dogs was also confirmed by Western blot and reverse transcription polymerase chain reaction analyses. It was concluded that treatment with a beta 3-adrenergic agonist stimulates UCP expression, which may lead to an increase in energy expenditure, and thereby is useful for the treatment and prevention of obesity in the dog.

Adipose Tissue, Brown↗
PubMed2002

Dual alpha(2)-adrenergic agonist and alpha(1)-adrenergic antagonist actions of dexmedetomidine on human isolated endothelium-denuded gastroepiploic arteries.

UNLABELLED: The actions of dexmedetomidine (DEX) on human vascular smooth muscle are unclear. We investigated its effects on isolated, endothelium-denuded human gastroepiploic arteries in vitro and compared them with clonidine (CLO). DEX had little direct effect on resting tension, whereas CLO produced small contractile responses, an effect which is blocked by the alpha(1)-adrenergic antagonist prazosin. DEX markedly enhanced the high K(+) (40 mmol/L)-induced contraction, and this effect was reversed by the alpha(2)-adrenergic antagonists yohimbine and rauwolscine but unaffected by prazosin. However, CLO had little effect on the K(+) contractions. Interestingly, larger concentrations (>10(-7) mol/L) of both alpha(2)-adrenergic stimulants significantly inhibited the contractions elicited by the alpha(1)-adrenergic agonist phenylephrine (10(-6) mol/L) and, to a lesser extent, those elicited by the alpha(1)/alpha(2)-agonist norepinephrine (10(-6) mol/L). These results suggest the possibility that DEX and CLO each have a high affinity for alpha(1)-adrenoceptors in human isolated gastroepiploic arteries, resulting in a reduced efficacy of alpha(1)-adrenergic activation by alpha-agonists. The differing affinities of the drugs for alpha(1)- and alpha(2)-adrenoceptors may help explain their additional actions: 1) DEX enhances the high K(+)-induced contraction presumably through alpha(2)-adrenoceptor activation, and 2) CLO acts on alpha(1)-adrenoceptors as a partial agonist when present alone. IMPLICATIONS: Dexmedetomidine may not directly affect smooth muscle in human peripheral resistance vessels within the usual range of plasma concentrations (<10(-7) mol/L) achieved in clinical practice. However, in large doses, it could enhance the response to nonadrenergic vasoconstrictor agonists while antagonizing the vasoconstrictor response to alpha(1)-adrenoceptor agonists.

Adrenergic alpha-2 Receptor Agonists↗
PubMed1987

Pharmacokinetics and excretion of unique beta-adrenergic agonists.

beta-Adrenergic agonist analogs (congeners) of isoproterenol in which the N-isopropyl group has been linked to a p-methyl- (119) or p-trifluoromethyl- (143) anilide moiety through a four carbon methylene spacer have been investigated with respect to their plasma pharmacokinetic profiles and biliary and urinary elimination characteristics in rats. In spite of the differences in selectivity of pharmacologic effects and durations of action between these unique beta-adrenergic agonists and isoproterenol, no differences were observed in their pharmacokinetic parameters in plasma after intravenous administration. Plasma clearances were rapid (67-78 ml/min) and the compounds were widely distributed. In contrast to the known elimination characteristics of isoproterenol, biliary excretion was the major pathway for elimination of 119 and 143. Parent drug and 'one' major metabolite peak appeared in HPLC chromatograms of bile collected from rats that received 119 and 143 by intravenous administration. Preliminary evidence suggests that this metabolite peak consists of one or more glucuronide and/or sulfate conjugates. Urinary excretion appears to be of lesser quantitative importance for 119 and 143 than for isoproterenol. The protracted duration of residence of the derivatives in the heart may help to explain the unusual effects and tissue-specific pharmacological properties of these unique beta-adrenergic agonists.

Adrenergic beta-Agonists↗
PubMed1994

[Mechanisms of the analgesic effect of alpha 2 adrenergic agonists].

Alpha 2 adrenergic agonists stimulate specific receptors in the dorsal horn of the spinal cord leading to blockade of potassium and calcium channels. Presynaptic alpha 2 receptors inhibit the release of substance P and other neuropeptides which stimulate transmission of nociceptive stimulations. Post-synaptic alpha 2 receptors hyperpolarize neurons membranes and decrease the activity of nociceptive neurons. In addition, alpha 2 adrenergic agonists have a synergistic action with opioid and cholinergic agonists.

Adrenergic alpha-Agonists↗
PubMedDate not supplied

Activation of carbonic anhydrase by beta-adrenergic agonists and inhibition by beta-adrenergic blockers.

Knowing the in vitro and in vivo gastric secretory effects of beta-adrenergic agonists and antagonists, as well as the role of carbonic anhydrase in the gastric HCl production, we investigated the effect of some beta-adrenoceptor agonists (isoprenaline and orciprenaline) and antagonists (propranolol, timolol, atenolol, pindolol, acebutolol, metoprolol, exoxprenolol) on the purified, human red blood cell and gastric mucosa carbonic anhydrase. All the drugs were added to enzymatic preparations in a concentration range of 10(-7)-10(-3) M, the enzymatic activity being determined according to Maren's micro-method. Dose-response relationships were plotted for each drug. The activating effect of the beta-adrenergic agonists isoprenaline and orciprenaline on all the three species of carbonic anhydrase was dose-dependent, maximum effect being reached at 10(-3) M, when a highly significant (p less than 0.001) enzymatic activation was achieved. Beta-adrenergic blocking drugs decreased significantly the activity of carbonic anhydrase, thus, the activity of purified enzyme decreased with propranolol depending on the dose from 2140 +/- 68 to 1060 +/- 82 I.U. (p less than 0.001), that of red blood cell enzyme from 3340 +/- 280 to 1050 +/- 180 I.U. (p less than 0.001) and that of gastric mucosa enzyme from 2.1 +/- 0.2 to 1.1 +/- 0.1 E.U./mg bioptic sample. They also antagonized dose-dependently the activating effect of beta-adrenergic agonists on the enzyme. The results suggest that carbonic anhydrase might be one of the sites of beta-adrenoceptors, further studies using specific radioligands being necessary to elucidate whether these effects represent the interaction of these drugs with their specific receptor or if they are unspecific pharmacologic effects.

Adrenergic beta-Agonists↗
PubMed2002

Clinical and physiological effects of an acute alpha-1 adrenergic agonist and a beta-1 adrenergic antagonist in chronic orthostatic intolerance.

BACKGROUND: Adrenergic agents are commonly used in the treatment of chronic orthostatic intolerance with postural tachycardia syndrome (POTS). POTS may be associated with increased limb blood flow ("high flow") and defective orthostatic vasoconstriction or decreased limb blood flow ("low flow") and potentially with small blood volume. METHODS AND RESULTS: We investigated the consequences of short-term intravenous administration of an alpha-1 adrenergic agonist, phenylephrine, and a beta-1 adrenergic antagonist, esmolol, in 14 patients with POTS aged 13 to 19 years. Indices of heart rate and blood pressure variability, peripheral blood flow, and arterial resistance were assessed, and the capacitance relation was computed for every subject using venous occlusion plethysmography. Patients were tilted to 35 degrees upright while medicated and while unmedicated, and measurements were repeated. Phenylephrine improved orthostatic tolerance and normalized hemodynamics and indices of heart rate/blood pressure variability while supine and while upright, producing significant peripheral vasoconstriction and venoconstriction (20% capacitance change). Esmolol did not improve orthostatic tolerance or hemodynamics. A subgroup of low-flow POTS patients had exaggerated venoconstriction to phenylephrine (50% capacitance change) but others had no response. CONCLUSIONS: Phenylephrine, but not esmolol, improves orthostatic tolerance and hemodynamics in POTS. This lends support to the use of oral alpha-1 agonists in the treatment of patients with chronic orthostatic intolerance.

Adolescent↗
PubMed1989

Inhibition of adenylate cyclase in bovine ciliary process and rabbit iris ciliary body to alpha 2-adrenergic agonists.

Alpha 2-adrenergic inhibition of adenylate cyclase in bovine ciliary processes and rabbit iris ciliary body (ICB) was studied. With bovine ciliary process membrane, it was found that cAMP production in the presence of 1 microM isoproterenol was increased with increasing NaCl concentrations from 0 to 200 mM. Clonidine, an alpha 2-adrenergic agonist, produced a NaCl concentration-dependent inhibition of cAMP production in the presence of isoproterenol with a maximum inhibition at 200 mM NaCl (P less than 0.05). NaCl concentrations had no effect on basal adenylate cyclase activities and activity in the presence of clonidine alone. The alpha 2-adrenergic agonists, lofexidine, clonidine and p-amino-clonidine were tested for their ability to inhibit isoproterenol-stimulated adenylate cyclase in bovine ciliary process membrane in the presence of 200 mM NaCl. Their dose-response curves showed that they had similar IC50's but the maximum inhibition differed among these agonists. Clonidine was found to be a partial agonists producing 55% of the inhibition obtained with lofexidine. The specificity of inhibition of isoproterenol-stimulated adenylate cyclase by alpha 2-agonists and blockade by pertussis toxin was examined by adenine labelling in rabbit ICB. The results demonstrate that alpha 2-adrenergic receptors exert specific inhibitory effects on adenylate cyclase activity in rabbit ICB, which are mediated by an inhibition guanine nucleotide regulatory protein, Gi.

Adenine↗
PubMed1989

Evidence that rat pineal thyroxine 5'-deiodinase is primarily stimulated by beta- and not alpha-adrenergic agonists and that its adrenergic-stimulated and spontaneous rhythmic nocturnal rise require RNA and protein synthesis.

Pineal thyroxine 5'-deiodinase (5'-D) activity rose greater than 10-fold above the basal level 2-3 hr after 1 mg/kg isoproterenol and returned to near the basal level by 6 hr. The same dose of norepinephrine or phenylephrine was without effect, but phenylephrine modestly potentiated isoproterenol-stimulated 5'-D activity. Either actinomycin D or cycloheximide treatment markedly decreased diurnal isoproterenol stimulation and the spontaneous rhythmic nocturnal rise of pineal 5'-D. The data indicate that pineal 5'-D activity is very similar to pineal serotonin N-acetyl transferase in being primarily stimulated by beta-adrenergic agonists and requiring new RNA and protein synthesis for its activation.

Adrenergic alpha-Agonists↗
PubMed1981

Bronchodilation and inhibition of induced asthma by adrenergic agonists.

In asthma, adrenergic agonists alleviate airflow obstruction and prevent obstructive responses to a variety of stimuli. A rapidly and a slowly metabolized agonist were compared to determine whether bronchodilation is the major mechanism by which these drugs prevent exercise-induced asthma (EIA). A 200-microgram inhaled dose of the rapidly metabolized agonist, isoproterenol, induced bronchodilation of the same order as terbutaline 500 microgram (1-sec forced expiratory volume [FEV1] increased 9.5% and 10.2%). An hour after isoproterenol, FEV1 was still above baseline (p less than 0.02) but EIA was only partially inhibited; the 23% fall in FEV1 was of the same order as the 32% fall after placebo (p greater than 0.05). One hour after terbutaline, mean resting FEV1 was in the range of that after isoproterenol, but the 10% change after exercise was less than that after placebo and isoproterenol (p less than 0.005). Our findings suggest that the two effects have different dose-response relationships, with higher doses of adrenergic agonists needed to prevent EIA than to maintain bronchodilation.

Adolescent↗