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PubMed1981

Sympathomimetic amine-induced release of norepinephrine-3H from different intraneuronal storage compartments.

The effects of different loading procedures on norepinephrine-3H (NE-3H) efflux induced by a structurally analogous group of indirectly acting sympathomimetic amines was examined in rabbit vas deferens. (+)-Amphetamine was ineffective in releasing 3H from tissues with intact intraneuronal storage granules but was an effective depletor of (a) non-granular intraneuronal compartment(s) following in vivo treatment with reserpine. (+/-)-p-Hydroxynorephedrine was a less effective depletor of non-granular NE-3H. These experiments provide further evidence in support of multiple intraneuronal storage compartments which can be pharmacologically differentiated by utilizing indirectly acting sympathomimetic amine agents.

Animals↗
PubMed1995

Therapeutic trial of sympathomimetics in three cases of complete heart block in the fetus.

BACKGROUND: A total of 36 fetuses with isolated congenital complete heart block and structurally normal hearts have been seen in the department of fetal echocardiography since 1980. Although the prognosis is good in the majority of cases, those who develop intrauterine cardiac failure have a high mortality. The aim of this study was to investigate the contribution to management of sympathomimetic therapy by comparing two possible agents administered to the mothers. METHODS AND RESULTS: The effect of two sympathomimetic agents, isoprenaline and salbutamol, was compared in three patients with isolated complete heart block. Fetal heart rate and indexes of cardiac function were monitored during therapy. Maternal cardiovascular status was also regularly assessed. Dosage of isoprenaline increased from 1 to 12 micrograms/min, and salbutamol increased from 4 to 64 micrograms/min during the trial. No significant change was detected with isoprenaline therapy, but all fetuses showed an increase in heart rate and improvement in ventricular function with salbutamol. Salbutamol was maintained until delivery in one case with evidence of cardiac failure, with resolution of fetal hydrops. All three delivered in good condition close to term. Two of three required pacing in the neonatal period. CONCLUSIONS: We conclude that salbutamol can be effective in the treatment of fetal complete heart block and should be considered in patients with this condition where there is evidence of deteriorating cardiac function.

Albuterol↗
PubMed1985

Beta-adrenoceptor blockade and intrinsic sympathomimetic activity--relevance in the treatment of ischaemic heart disease.

Beta adrenoceptor blockade has become one of the major therapeutic interventions in the medical management of ischaemic heart disease over the last 15 years. A number of beta adrenoceptor blockers have been developed with differing pharmacological properties including cardioselectivity and intrinsic sympathomimetic activity (ISA). The relevance of this latter property has been in some doubt. A number of reports suggest that ISA confers haemodynamic benefits although there does not appear to be any clear therapeutic advantage. In addition it would appear that patients with severe or rest angina might benefit more from a pure beta antagonist rather than one with ISA when the beta blocker is used as monotherapy, but this situation rarely arises. This paper reviews and assesses the value of treatment of ischaemic heart disease with beta blockers possessing intrinsic sympathomimetic activity.

Adrenergic beta-Antagonists↗
PubMed1980

Sympathomimetic amines.

The autonomic nervous system may play an important role in tissue autoregulation as the neurohumoral transmission process has been shown to constitute the final common pathway by which the effects of many physiological and pharmacological substances are mediated. The effects of the administration of a sympathomimetic amine cannot be accurately predicted in a subject. Choice of which sympathomimetic amine to use should be determined on the basis of data obtained in relevant clinical circumstances, but the dose should always be titrated against the effect in each individual. It is interesting that adrenaline, "the original autonomic drug" with its "venerable history", is still a first line drug in many of the situations for which it was being prescribed in 1907. It is the drug of first choice in anaphylactic reactions and for severe allergic bronchospasm, and is widely used as a vasoconstrictor in surgery and with local anaesthetic agents. Adrenaline in "physiological" doses is a satisfactory and cheap alternative to other available drugs for use in septic shock and in emergence from cardiopulmonary bypass.

Action Potentials↗
PubMed1990

Sympathomimetics for acute severe asthma: should only beta 2-selective agonists be used?

Sympathomimetics have become a mainstay of the treatment of acute asthma. Aerosolization of sympathomimetics provides as great or greater bronchodilation in acute severe asthma with fewer systemic effects than parenteral therapy. Despite the broncho-selectivity achieved with this route of administration, cardiostimulation remains the major, dose-limiting factor in the safe use of sustained, high-dose therapy with these agents. This article reviews the pharmacology, adverse effects, and toxicities of selected beta agonists, as well as clinical studies relevant to the question posed in the title. Although the ideal study to answer this question has not yet been performed, the authors feel that available evidence supports the preferential use of selective beta 2 agonists in patients with acute, severe asthma who will require high doses of beta agonists.

Acute Disease↗
PubMed2003

The sympathomimetic actions of l-ephedrine and d-pseudoephedrine: direct receptor activation or norepinephrine release?

UNLABELLED: The basic mechanisms by which ephedrine is preferred over other vasopressors in obstetric anesthesia have not been clearly defined. We examined the sympathomimetic effects of l-ephedrine, currently used as a vasopressor, and d-pseudoephedrine, currently used as a decongestant. In anesthetized rats, l-ephedrine and d-pseudoephedrine caused dose-dependent increases in arterial blood pressure and heart rate, and these effects disappeared after destruction of the sympathetic nerve terminals with 6-hydroxydopamine (6-OHDA) pretreatment. The two ephedrine isomers produced concentration-dependent increases in tension of anococcygeal muscle and sinus rate of right atrium from rats. However, the anococcygeal and atrial responses to d-pseudoephedrine were abolished after 6-OHDA pretreatment, whereas approximately 50% of the responses to l-ephedrine were 6-OHDA-resistant. In human umbilical artery and vein, the two isomers failed to generate any contraction when given at the concentration that is capable of producing significant effects on anococcygeal and atrial tissues. Although direct adrenoceptor activation with l-ephedrine was detectable at tissue levels, the pressor response in vivo was entirely attributable to norepinephrine release from sympathetic nerves. This indirect mechanism could partly explain why l-ephedrine is better at increasing maternal arterial blood pressure while preserving the uteroplacental blood flow that is devoid of the involvement of the sympathetic innervation. IMPLICATIONS: The indirectly sympathomimetic property of l-ephedrine may be one of the mechanisms to explain why ephedrine is preferred over alpha-adrenergic agonists as a vasopressor for treatment of intraspinal anesthesia-induced hypotension in obstetrics.

Animals↗
PubMed1980

Effect of local application of sympathomimetic drugs to the epididymis on fertility in rats.

Insertion of Silastic rods containing the directly acting sympathomimetic drug, methoxamine, adjacent to the epididymis of rats caused a temporary reduction in fertility with no loss of ability to mate. This effect lasted up to 3 weeks. At the time of the maximal antifertility action (3-7 days after insertion), the number of spermatozoa in the ejaculate fell to almost zero, and there was a reduction in the total number of spermatozoa in the epididymis resulting from a significant drop in the number present in the cauda. Methoxamine also caused immotility and decapitation of the remaining epididymal spermatozoa. The indirectly acting sympathomimetics, tyramine and norephedrine, did not affect fertility. It is postulated that methoxamine acts to induce infertility principally by bringing about a reduction of sperm numbers in the ejaculate. This could have been produced either by a failure of the vas and cauda to contract normally at copulation or because the sperm store in the cauda had fallen below a critical threshold level.

Animals↗
PubMed1976

Thin layer chromatographic identification of some sympathomimetic amines.

Thin layer chromatographic behavior of some sympathomimetic amines in the presence of acids in neutral and organic solvent systems is reported. The sympathomimetic amines were dissolved in 0.1N HCl or ethanol and treated with bromocresol green or p-nitrobenzoyl chloride reagents on fiber sheets or precoated glass plates. Two-, 3-, and 4-, component solvent systems were tested. Benzene-ethyl acetate gave 2 spots for each amine standard; the more polar spots were satisfactorily separated. Amines in pharmaccuticals were not separated by any solvent system tested.

Amines↗
PubMed1975

Abnormal secretory response to parasympathomimetic and sympathomimetic stimulations from the submaxillary gland of rats treated with reserpine.

Rats treated with 0.5 mg/kg of reserpine per day for 7 days were anesthetized and submaxillary saliva was collected and analyzed for Na+, K+, Ca++ and protein concentrations. Salivary secretion was elicited by i.p. injections of carbamylcholine (50-100 mug/kg), phenylephrine (5 mg/kg) and isoproterenol (10 mg/rat). Saliva was also collected from untreated controls. Submaxillary glands were excised from both groups of animals at the termination of the secretory response, homogenized and analyzed. Glands from other animals were removed in the resting state and similarly processed. Pretreatment with reserpine resulted in decreased volumes of salvia and in elevated salivary concentrations of Ca++ and protein. Saliva from the reserpine-treated animals secreted in response to carbamylcholine had higher concentrations of Na+ and K+ than control saliva, particularly at the low rates of flow. Saliva secreted after stimulation with the two sympathomimetic secretagogues had lower concentrations of these two ions. Resting glands from the treated animals showed significant elevations in protein and Ca++ content and a significant decrease in K+ content. At the end of the secretory response to the three secretagogues, glands from treated animals showed a significantly higher Na+ content and a significantly lower K+ content than control glands. It is concluded that pretreatment with reserpine alters the secretory response of the rat submaxillary gland to both parasympathomimetic and sympathomimetic stimulation. This alteration results from a toxic lesion caused by reserpine in the salivary cells, which involves changes in their permeability to ions and in their energy resources. These in turn, result in an abnormal stimulus-secretion coupling mechanism. The possibility that the toxic lesion is related to alterations in Ca++ homeostasis is discussed.

Animals↗
PubMed1991

Bromocriptine-associated headache: possible life-threatening sympathomimetic interaction.

We present two cases of severe headache associated with the use of bromocriptine for lactation suppression in otherwise healthy women. In each case, the additional use of a therapeutic sympathomimetic agent resulted in extreme worsening of symptoms with development of hypertension and life-threatening complications (ventricular tachycardia and cardiac dysfunction in one case, seizures and cerebral vasospasm in the other). Sympathomimetics in combination with bromocriptine in patients with a bromocriptine-associated headache during the puerperium may be dangerous.

Adult↗
PubMed1990

Naloxone potentiation of cardiovascular responses to sympathomimetic amines in the rat.

The work was aimed at analyzing the ability of naloxone to potentiate 1) the arterial pressure responses to sympathomimetic amines administered i.v. in normotensive anesthetized, pithed, chemically sympathectomized or acutely adrenalectomized rats and 2) the chronotropic responses to norepinephrine in the isolated rat atria. In anesthetized rats, naloxone (2.5-10 mg/kg i.v.) potentiated the pressor responses to epinephrine (2 micrograms/kg). Naloxone (5 mg/kg) significantly potentiated the pressor responses to norepinephrine (1-4 micrograms/kg), phenylephrine (10-50 micrograms/kg) and the reflex pressor responses to a 60-sec carotid occlusion. On the contrary, naloxone did not potentiate the arterial pressure responses to methoxamine (100 micrograms/kg), angiotensin (0.5-2 micrograms/kg) and isoproterenol (1 micrograms/kg). Pithing or acute adrenalectomy did not alter the naloxone-induced potentiation of the pressor responses to norepinephrine (0.125-0.5 micrograms/kg). 6-Hydroxydopamine pretreatment abolished completely the naloxone-induced potentiation of the pressor responses to norepinephrine (0.25-1 micrograms/kg). In isolated rat atria, naloxone (1.4 and 2.8 x 10(-5) M) potentiated the chronotropic responses to norepinephrine (1.5-6 x 10(-8) M). It is suggested that naloxone potentiates cardiovascular responses to sympathomimetic amines by interacting with presynaptic adrenergic mechanisms which could additionally contribute to its pressor effects in acute hypotensive conditions.

Angiotensins↗
PubMedDate not supplied

Mechanism of action of nicotine in isolated urinary bladder of guinea-pig: involvement of tachykinin(s) released by nicotine in the drug's sympathomimetic effect.

A sympathetic neurone blocking drug, guanethidine, and a tachykinin antagonist, [D-Arg1, D-Pro2, D-Trp7,9, Leu11]-substance P (rpwwL-SP), partially inhibited the contractile response to nicotine to the same degree in the isolated detrusor strips of guinea-pig urinary bladder. Application of rpwwL-SP completely abolished the inhibitory effect of guanethidine on the nicotine-induced contraction, suggesting that the tachykinin(s)-ergic transmission might be involved in the sympathomimetic effect of nicotine. Conversely, when the preparation was treated with guanethidine to block release of a mediator from the sympathetic nerve, the inhibitory effect of rpwwL-SP was diminished, suggesting an exclusive contribution of the sympathetic nerve communications to the action of the tachykinin(s). We previously suggested that nicotine may release acetylcholine and ATP to contract the detrusor strips, and that acetylcholine output may be increased by an unknown substance released from the sympathetic nerve by nicotine. In preparations treated with atropine, rpwwl-SP had no effect on the nicotine-induced contraction. The concentration-response curves for carbachol and ATP were not influenced by rpwwl-SP. After tachyphylaxis to capsaicin developed, the nicotine-induced contraction was not affected. It is suggested that in guinea-pig detrusor, tachykinin(s) from capsaicin-insensitive sites is (are) involved in the excitatory sympathomimetic effect of nicotine, and that the tachykinin(s) behave(s) as a modulator finally to increase the acetylcholine output from the parasympathetic cholinergic nerve.

Adenosine Triphosphate↗
PubMed1989

Sympathomimetics in acute severe asthma: inhaled or parenteral, nebulizer or spacer?

It is accepted today that all patients with acute asthma should be treated with a sympathomimetic, irrespective of previous therapy. This short review addresses the question of the optimal mode of administration of these drugs in acute severe asthma. Inhaled sympathomimetics are as effective as subcutaneous adrenaline, or intravenous salbutamol or terbutaline, and, as they produce fewer side-effects, are recommended as the best mode of administration. However, self-medication with a ready to use subcutaneous preparation may be indicated in those patients prone to very abrupt attacks. The conventional mode of inhalation therapy in acute asthma is nebulization, but equally effective bronchodilatation may be obtained with metered-dose inhalers combined with valved spacers. Tachypnoeic patients unable to perform a conventional inhalation manoeuvre can use one-way valve inhalation devices with repeated tidal breaths. Finally, sequential or even continuous inhalation techniques have recently been advocated, particularly in patients with impending respiratory failure.

Administration, Inhalation↗
PubMed1987

Beta-sympathomimetic agents: use in perinatal obstetrics.

Beta-sympathomimetic agents are used extensively in obstetrics to inhibit premature labor. Knowledge of the pharmacology, mode of action on smooth muscle, and cardiovascular and metabolic side effects of these agents is essential for the obstetrician and perinatologist. This review article draws extensively on recent animal research data to explain mechanisms of action and long-term effects of beta-sympathomimetic agents.

Animals↗
PubMedDate not supplied

Influence of castration and of the kind of sympathomimetic drug used upon the reactivity of rat seminal vesicles.

An interdependence of the hormonal state of rodents and the genital muscle response to drugs was observed either on females or on males. Castration or castration followed by oestradiol treatment increased the responses of rat seminal vesicles to parasympathomimetic drugs. As, however, the influence of such procedures upon the responses to sympathomimetic drugs is controversial, the parameters pD2 (apparent affinity constant), alpha (intrinsic activity) and rho (relative responsiveness) of adrenaline, noradrenaline, methoxamine and phenylephrine on the seminal vesicles isolated from normal and castrated rats were determined. These parameters were shown to be different, depending not only of the hormonal state of the donor animals, but also of the drugs tested on each preparation. These facts must be considered in studies about sensitivity of rat seminal vesicles to sympathomimetic drugs.

Animals↗
PubMed1986

[Use of sympathomimetic agents in the treatment of acute circulatory insufficiency in the immediate postoperative period of heart surgery patients].

Sympathomimetic agents: isoproterenol (novodrin), dopamine, noradrenalin, adrenalin were used in 137 patients with acute circulatory insufficiency. Their hemodynamic effects were assessed, using catheterization of heart chambers and radiocardiography, and studies of circulating blood oxygen transport, acid-base state and metabolic product levels. A differential approach to sympathomimetic treatment has been developed. Isoproterenol is primarily indicated in those cases where myocardial failure is combined with decreased heart rate, conductivity disorders and markedly increased total peripheral resistance. Dopamine is more justified in cases where increasing the heart rate is more desirable, and there are signs of renal failure and heart rhythm disorders. The possibility of dopamine-induced pulmonary hypertension and pO2 fall should not be dismissed. Correct choice of an agent or a combination of agents makes it possible to control the patient's condition through action on various hemodynamic mechanisms that determine the magnitude of cardiac output.

Acute Disease↗
PubMed1966

Effect of sympathomimetic compounds with beta-adrenergic effects on plasma free fatty acids in man.

Nine sympathomimetic compounds were infused intravenously in man, and their effects on the level of plasma free fatty acids, pulse rate, and blood pressure were recorded. Each compound raised the level of plasma free fatty acids. Its activity in this respect could be correlated with its activity in producing Beta-adrenergic effects on the circulation; both effects were abolished by pretreatment with propranolol. It is concluded that sympathomimetic compounds that stimulate -receptors will raise the plasma concentration of free fatty acids.

Fatty Acids↗
PubMed1980

[Suppression, by beta-adrenergic receptor blockade, of the sympathomimetic component of dopamine renal action in water-saline depletion].

The effects of beta-adrenergic receptor blockade on the renal action of Dopamine (DA) in hydro-saline depletion were investigated in 9 healthy subjects. The beta-adrenergic blocking treatment was performed (Propranolol hydrochloride 2.4 mg/kg b.w. per day) during the 2 days preceding the renal function studies. For other experimental details, see our previous Note (11). In the presence of beta-adrenergic blockade DA effects in hydro-saline depletion consisted of: a) an increase in both RPF and GFR; b) a decrease in sodium abnormally isoosmotic reabsorption as % of sodium distal load; c) an increase in both sodium and osmolar clearances; d) an increase in free water clearance higher than that observed in the absence of blocking treatment. Therefore, the sympathomimetic effects of DA in hydro-saline depletion appear to be suppressed by beta-adrenergic blockade. It is suggested that such sympathomimetic action of DA may be mediated by beta-presynaptic receptors of noradrenergic nerve endings.

Adrenergic beta-Antagonists↗