Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “SYMPATHOLYTICS”

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 937 records · Page 52Linked to original sources
PubMed1984

Comparative effects of antihypertensive therapy with guanabenz and propranolol on renal vascular resistance and left ventricular mass.

There is increasing interest in initial therapy of hypertension with sympatholytic agents and the influence of antihypertensive therapy on cardiac and renal function. We treated 26 men with essential hypertension with either guanabenz alone (n = 14) or propranolol alone (n = 12) and assessed blood pressure and renal perfusion before and after 5-7 weeks of treatment. Cardiac performance was evaluated for the guanabenz-treated patients. Both drugs substantially reduced blood pressure without weight gain. During guanabenz therapy, glomerular filtration rate and renal blood flow were preserved, with a fall in renal vascular resistance (from 12,100 +/- 1,500 to 9,300 +/- 1,190 dyne X s X cm-5, p less than 0.01). Propranolol decreased glomerular filtration rate (from 95 +/- 11 to 70 +/- 6 ml/min, p less than 0.05) without significant change in renal blood flow or renal vascular resistance. In guanabenz-treated patients, there was a decline in left ventricular mass (from 290 +/- 23 to 257 +/- 14 g, p = 0.067). Thus, both agents are effective initial therapy in hypertension. Guanabenz treatment also was associated with reduced renal vascular resistance and left ventricular mass.

Adult↗
PubMed1980

[Effect of ethanol and toliprolol on the carbohydrate metabolism of the brain and liver].

After application of ethanol (1.5 mg/g i.v.) to mice, the content of glycogen of the liver and the brain decreased. The alterated content of the metabolites of the glucose break-down points to an augmentation of the glycolysis in the liver and a diminution of the glycolysis in the brain. By pretreatment with the beta-sympatholytic agent 1-isopropylamino-3-(3-tolyloxy)-2-propanol (toliprolol, Doberol) (50 microgram/g s.c.), the ethanol-induced break-down of glycogen was partially blocked in the liver and completely abolished in the brain. In contrast, mainly synergistic effects of ethanol and toliprolol on the glycolysis of the liver and the brain were found. From the results it is concluded that the ethanol-induced break-down of glycogen is mediated, at least in part, by catecholamines whereas the alteration of the glycolysis by ethanol is brought about by some different mechanism.

Adrenergic beta-Antagonists↗
PubMed1980

Modern concepts in the drug treatment of arterial hypertension.

The present survey paper, concerning newer drugs used in the treatment of arterial hypertension, deals with the following types of agents: centrally acting drugs, such as clonidine nd alpha-methyl-DOPA; vasodilator drugs with a direct action on smooth muscle, such as minoxidil; diuretic agents, with special reference to the choice of a drug from the vast number of compounds; beta-sympatholytic drugs (beta blockers) and which drug to choose; prazosin, with special reference to its considerable theoretical interest; drugs that influence the renin-angiotensin system, such as saralasin (P 113), an angiotensin II-antagonist; and inhibitors of the converting enzyme, such as teprotide (SQ 20,881) and captopril (SQ 14,225). Finally, a general schedule for the treatment of hypertension, issued as a guideline by the Dutch Institution of General Practitioners, is presented.

Adrenergic beta-Antagonists↗
PubMed1981

[Neuropharmacologic regulation of the carcinogenic action of 1,2-dimethylhydrazine].

Chronic experiments were made on 100 male rats to examine the modifying effects of adrenergic and cholinergic agents that regulate homeostasis on 1,2-dimethylhydrazine-induced intestinal carcinogenesis. The sympatholytic guanethidine (5 mg/kg) and the alfa-adrenoblocker butyroxan (2.5 mg/kg) did not influence the carcinogenesis in the intestine. The noradrenaline- and atropine-induced (1 mg/kg and 10 mg/kg) increase in the adrenergic component of the vegetative nervous system led to the decrease in the number (by 2-3 times) and size of the tumor nodes in the intestine. The drugs did not affect the morphology of neoplasms. The results are discussed in terms of essential importance of the vegetative nervous system in the mechanism of chemical carcinogenesis.

1,2-Dimethylhydrazine↗
PubMed1983

Effect of the centrally acting agent clonidine on circulating catecholamines at rest and during exercise. Comparison with the effects of beta-blocking agents.

To determine the amount of sympathetic outflow suppression due to the alpha 2-adrenergic receptor stimulating agent clonidine, its effect on heart rate, blood pressure, and on circulating plasma catecholamines was assessed in ten healthy subjects at rest and during submaximal ergometric exercise. Similar exercise studies were performed in eight healthy normotensive persons after beta-blockade using propanolol. In nine healthy subjects the effect of an acute intravenous (IV) intervention of clonidine on plasma catecholamines was compared with the results obtained after IV administration of the cardioselective beta-blocker metoprolol or of both drugs. Clonidine taken orally produced significantly reduced plasma levels of epinephrine and norepinephrine (p less than 0.01). During submaximal ergometric exercise, the sympatholytic effect of clonidine was relatively less marked than at rest (p less than 0.05). After beta-blockade, either orally with propanolol or IV with metoprolol, plasma catecholamines at rest did not change significantly; their plasma levels during exercise, however, exceeded those obtained after administration of placebo (p less than 0.05). Giving IV clonidine and metoprolol combined revealed no significant changes of plasma catecholamines at rest and during exercise; heart rate and blood pressure decreased significantly (p less than 0.001). Clonidine on the one hand and the beta-blocking agents on the other exhibit oppositely directed effects on plasma levels of catecholamines.

Adrenergic beta-Antagonists↗
PubMed1983

Postsynaptic alpha 1- and alpha 2-adrenoceptor blocking properties of (dihydro)quinidine and (dihydro)quinine.

The antagonistic properties of the cinchona alkaloids quinidine, dihydroquinidine, quinine and dihydroquinine were evaluated with respect to alpha 1- and alpha 2-adrenoceptor-induced vasoconstriction in pithed normotensive rats. Radioligand displacement studies were performed to determine the in vitro affinities of the alkaloids for alpha 1- and alpha 2-adrenoceptors. Quinidine and dihydroquinidine were more effective alpha 1-adrenoceptor antagonists than quinine and dihydroquinine. Their weak to moderate alpha 1-sympatholytic activities were compatible with their in vitro affinity for alpha 1-adrenoceptors. The potencies of (dihydro)quinidine and (dihydro)quinine in inhibiting vascular postsynaptic alpha 2-adrenoceptor-mediated pressor effects were also weak and comparable in the lower dose range (15-250 mumol kg-1). In a dose of 300 mumol kg-1, dihydroquinidine exceeded the other alkaloids in activity. The alpha 2-adrenoceptor antagonistic actions of the alkaloids did not correspond with their actual affinity for alpha 2-adrenoceptors observed in vitro. A calcium antagonistic action is proposed to contribute to the interference of these drugs with the vasoconstriction governed by alpha 2-adrenoceptors. The interaction of quinine, quinidine and their hydrogenated products with vascular alpha 1- and alpha 2-adrenoceptors may explain their hypotensive properties as well as their therapeutic effect in certain forms of vascular disorders.

Adrenergic alpha-Antagonists↗
PubMedDate not supplied

[Effect of the tetracyclic antidepressants pyrazidol and inkazan on the adrenergic nerve transmission in the rat vas deferens].

The effect of new tetracyclic antidepressants pyrazidol and inkazan on adrenergic neurotransmission in the isolated rat vas deferens was studied by examining vas deferens contractions in response to the transmural electric stimulation of the postganglionic sympathetic nerves and addition of noradrenaline (NA) or BaCl2. Pyrazidol and inkazan were found to be capable to increase vas deferens contractions in response to transmural electric stimulation or addition of NA. When given in high concentrations, these antidepressants inhibit the adrenergic neurotransmission since inkazan possesses low sympatholytic activity and pyrazidol exhibits certain alpha-adrenolytic effect.

Animals↗
PubMed1982

[Pharmacodynamics of alizapride (author's transl)].

Studies of alizapride (N[(allyl-1 pyrrolidinyl-2) methyl] méthoxy-2 azimido-4,5 benzamide hydrochlorate) in mice and rats demonstrated little toxicity, particularly after parenteral administration. Alizapride's main pharmacodynamic effects are on the central nervous system. It is very effective against emesis induced by apomorphine and dihydrogenated ergot alkaloids in dogs. In this respect it is three times more effective than metoclopramide. In contrast to neuroleptics, alizapride does not modify equilibrium reflexes in mice, nor does it reinforce hypnosis induced by barbiturates. Only minor central antidopaminergic effects were recorded, less marked than those seen with metoclopramide. In mice, alizapride has no anticonvulsant or analgesic effects. It has little action on the autonomic nervous system or on the cardiovascular system. Alizapride has no antihistaminic or parasympatholytic effect. In dogs, sympatholytic effects and hypotension are seen only after giving a much higher dose than that which is effective against apomorphine and dihydrogenated ergot alkaloids.

Animals↗
PubMed1982

Hypotensive properties of benzodioxane derivatives structurally related to R 28935. Comparison of activity with some receptor affinities.

Hypotensive activities were determined of some derivatives of erythro 1-(1-[2-(1,4-benzodioxane-2-yl)-2-hydroxyethyl]-4-piperidyl)-2-benzimidazolinone (R 28935) following intravenous administration to anaesthetized normotensive rats. Introduction of chlorine into the benzimidazolinone part of R 28935 negatively influenced the hypotensive potency as did opening of the dioxane ring. An appropriate substituent restored the hypotensive effectiveness of the "opened" structures. In general, the compounds were weak inhibitors of the specific binding of (3H)-prazosin (alpha 1-adrenoceptors), (3H)-clonidine (alpha 2-adrenoceptors) and (3H)-dihydromorphine (opiate-receptors) to rat brain membranes. The relative order of affinity for either receptor did not correspond with that of the hypotensive activity. Previous (-15 min) intravenous treatment with phentolamine (0.2 mg/kg) abolished the depressor effect of prazosin and diminished that of the threo form R 29814 as well as of all "opened" congeners, but did not significantly reduce the hypotensive response to R 28935 and the other erythro structures. It is concluded that neither alpha 1- and alpha 2- nor opiate-receptors are involved as the primary targets for R 28935 and its congeneric drugs to induce hypotension. The exact mechanism of action remains therefore unsolved. Erythro R 28935 and the other racemic erythro mixtures are centrally acting hypotensive agents. A peripheral alpha-sympatholytic component may contribute to the overall depressor effect of threo R 29814 and the "opened" derivatives.

Anesthesia↗
PubMed1983

[Arterial hypertension in elderly patients, and difficulties in its treatment].

In treating elderly patients with hypertension, specific characteristics should be taken into account. These are related to general hemodynamics, renal function and neurohormonal systems. Medications are the same as those used in middle-aged hypertensive patients. In the elderly, management requires great caution because of maximum difficulties. Satisfactory clinical and biological tolerance is an essential goal. The best initial therapy seems to be a diuretic drug given in low dosages. Some patients may require addition of a central sympatholytic, a beta-blocking agent or a vasodilator.

Aged↗
PubMed1983

[Antihypertensive vasodilators].

Antihypertensive vasodilators share the capability of producing vasodilation of arterioles. In addition, two of them, i.e. nitroprussiate and prazosine, also produce vasodilation of veinulae. Both of these agents cause a simultaneous decrease in pre-load and post-load, and may be used in heart failure. The effectiveness of vasodilators is offset by regulatory cardiac and/or renal mechanisms, and the association with a sympatholytic agent and/or a diuretic is generally needed. Consequently, vasodilators are usually the third step in the course of managing a hypertensive patient. Association with a betablocking agent is especially necessary in patients with coronary insufficiency, in order to prevent an increase in myocardial oxygen requirements and worsening of angina pectoris. Vasodilators are active within a fairly wide dosage range, making individualized dosages requisite. In treating hypertension by the oral route, daily doses above 200 mg for dihydralazine, 60 mg for minoxidil and 10 mg for prazosine are only exceptionnaly useful. In emergency treatment of hypertension, diazoxide and nitroprussiate can be used only in patients under continuous cardiovascular monitoring. Nitroprussiate must, in addition, be given through a controlled infusion device, but ensures more flexible and safer control of blood pressure. Dihydralazine may produce headache. This side effect occurs very early and is hardly compatible with continuation of treatment. Long term side effects are very uncommon or strictly biological for dosages below 200 mg/day. With currently used dosages (20 to 60 mg per day) minoxidil consistently produces hypertrichosis, outruling its protacted use in women.(ABSTRACT TRUNCATED AT 250 WORDS)

Antihypertensive Agents↗
PubMed1984

Effects of captopril on the development of tolerance to guanethidine.

Guanethidine is a sympatholytic antihypertensive drug used for the treatment of severe or resistant hypertension. Previous clinical studies have documented the development of tolerance to guanethidine in humans and suggested that fluid retention or increased sensitivity of arterioles to endogenous catecholamines may be responsible for the tolerance development. In this study we investigated the role of the renin-angiotensin system in the development of tolerance to guanethidine in one-kidney, one-clip renovascular and spontaneously hypertensive rats (SHR) using the angiotensin-converting enzyme inhibitor captopril. In the one-kidney model, captopril (30 mg/(kg X day), orally) had no effect on the development of tolerance to guanethidine (50 mg/(kg X day), i.p.) when the drugs were coadministered for 2 wk. However, captopril enhanced the day 1 blood pressure-lowering effect and prevented the development of tolerance to guanethidine in male SHR. These results suggest that the renin-angiotensin system plays a major role in the development of tolerance to guanethidine in SHR but not in one-kidney, one-clip renal hypertensive rats. Thus, the etiology of the hypertensive state may dictate which physiological compensatory mechanisms are activated after antihypertensive drug administration.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1978

Responses of heart ornithine decarboxylase and adrenal catecholamines to methadone and sympathetic stimulants in developing and adults rats.

Sympathetic stimulation elevates heart ornithine decarboxylase (ODC) activity in adult rats, an effect which is followed by cardiac hypertrophy. In developing animals, adrenergic agonists play a role in cardiac growth and differentiation. Methadone administration to adult rats stimulated heart ODC, and this stimulation could be blocked by the sympatholytic agents chlorisondamine, reserpine or propranolol, suggesting that the effect is mediated via central stimulation of sympathetic nerves. With repeated methadone administration, tolerance developed to the heart ODC stimulation by methadone, eventually resulting in decreased heart ODC accompanied by deficits in heart weight. The sensitivity of the mature heart and adrenal medulla to the sympathetic stimulants insulin, nicotine or isoproterenol was virtually unchanged during long-term methadone administration, indicating that tolerance of the heart ODC response to methadone did not result from subsensitivity of the efferent sympathetic pathway or the heart ODC response system. In normally developing rats, responses to insulin-induced reflex stimulation of sympathetic nerve supplies to the heart and adrenal medulla did not occur until 8 days of postnatal age; however, daily treatment of pups with methadone begun the day after birth accelerated the development of functiona heart and adrenal medullary responses to insulin such that responses were obtained by 4 days of age. The cardiac responses to nicotine developed somewhat differently, with significant ODC stimulation first appearing at 12 days in controls and at 8 days in methadone-treated pups. In the adrenal gland, a tissue in which responses to nicotine do not depend on an intact nerve supply a catecholamine secretory response to nicotine was observed at 4 days of age in controls. These data suggest that methadone treatment accelerates the development of functional sympathetic innervation of heart and adrenal medulla, with resultant abnormalities in cardiac muscle growth and differentiation.

Adrenal Medulla↗
PubMed1978

The action of prazosin in human vascular preparations.

To identify the mode of action of prazosin, its effects on isolated human vascular preparations were studied. Isometric tension was recorded from spiral strips of dorsal metacarpal veins, common palmar digital arteries and uterine, splenic and ileocolic arteries. Prazosin was a potent antagonist of noradrenaline, but not 5-hydroxytryptamine or barium chloride in the metacarpal veins. Higher concentrations of prazosin were necessary to antagonize noradrenaline in the visceral arteries. The digital arteries were resistant to its sympatholytic effect. It is concluded that prazosin acts as an alpha-adrenoceptor antagonist of different potency in various vascular beds. It is postulated that the initial cardiovascular side effects of prazosin are due to venous pooling and that the long term antihypertensive effect is the result of reduced peripheral resistance because of interference with arterial sympathetic tone.

Barium↗
PubMed1984

Modulation of the adrenergic system in the treatment of postoperative bowel atonia.

Sympathetic hyperactivity is considered to be the most important factor in the development of postoperative bowel atonia. In a double-blind study we evaluated the gut motor effects of dihydroergotamine, which predominantly acts as a sympatholytic agent in the gastrointestinal tract. Forty-six patients undergoing cholecystectomy received either 0.5 mg dihydroergotamine + 5000 U heparin or 5000 U heparin alone (controls) twice daily in a randomized order starting on the morning of the operation. The first postoperative bowel movement occurred 57 +/- 4 h (means +/- SEM) after operation in the patients receiving dihydroergotamine, compared with 102 +/- 4 h in the control patients (p less than 0.001). Electromyography performed in the stomach and upper small bowel on the 3rd postoperative day showed an increase in the number of activity fronts of the interdigestive migrating motor complex and in the duration of spike activity under the influence of dihydroergotamine compared with the controls (p less than 0.001). It is concluded that dihydroergotamine stimulates depressed gut motility after abdominal surgery and that sympatholysis is the likely mechanism of action.

Adrenergic Fibers↗
PubMed1984

[Study on the functional development of the sympathetic nervous system of fetal heart in rats].

The drugs acting on the autonomic nervous system were administered intravenously to dams or intraperitoneally to the 20-day-old fetuses maintained by umbilical and placental circulation. The fetal heart rates were accelerated by the administration of isoproterenol, epinephrine, norepinephrine, tyramine and dopamine to fetuses, and they were decelecated by the injection of propranolol and methacholine to fetuses. However, the tachycardia caused by the fetal injection of isoproterenol and the bradycardia by methacholine were inhibited by the pretreatment of propranolol and atropine. The fetal bradycardia and hypoxia caused by the administration of epinephrine under the pretreatment of propranolol to fetuses were inhibited by the injection of alpha-adrenergic receptor blockers such as phentolamine and yohimbine. Furthermore, the tyramine treatment to fetuses produced significant acceleration of the fetal heart rate on day 19-20 of gestation, but not on day 18. These findings suggest that fetal cardiac beta-adrenergic, muscarine-cholinergic receptors and vascular postsynaptic alpha-adrenergic receptor may be sensitive enough to respond to sympathomimetic and sympatholytic drugs, and the fetal cardiac sympathetic innervation between the adrenergic nerve terminal and synapse effector cells may be developed on day 18-19 of gestation.

Animals↗
PubMed1976

[Drug interactions in cardiovascular therapy].

Cardiovascular therapy frequently requires simultaneous administration of several drugs. These drugs may interact pharmacokinetically or pharmacodynamically, and most drug interactions are therapeutically useful. The clinical importance of adverse drug interactions is often overestimated; they are almost always predictable and preventable, if their mechanisms are understood and the drug dosages appropriately modified. Coumarin anticoagulants and cardiac glycosides are involved in the most serious interactions. Diuretics, antiarrhythmic drugs, sympatholytics, sympathomimetics and monoamine oxidase blockers also interact in clinically significant fashion with other drugs.

Antidepressive Agents↗
PubMed1984

Development of tolerance to guanethidine in three hypertensive rat models.

The development of tolerance to the antihypertensive effects of guanethidine was determined in one-kidney one clip and two-kidney one clip renovascular hypertensive rats and spontaneously hypertensive rats (SHR). The effect of gender on the tolerance development was also studied in SHR. Although initial guanethidine administration acutely reduced arterial pressure in all hypertensive models, initial dose responsiveness to the blood pressure lowering effects of guanethidine (50 mg/kg, i.p.) was greatest in male SHR. After two weeks of daily guanethidine dosing (50 mg/kg/day, i.p.) only female SHR demonstrated an acute depressor response to the day 14 guanethidine dose. During the two week dosing interval tolerance development began after day 3 in all models, and systolic pressure (SP) was not significantly different from preguanethidine values in tolerant animals by day 7. In both renovascular hypertensive models a subpopulation of guanethidine responders was identified which maintained a lowered SP (p less than 0.05) after day 3. SHR demonstrated a high degree of tolerance after day 7 regardless of gender. Tolerance did not develop to the guanethidine-induced bradycardia in any model. These data suggest that both renovascular models and SHR are suitable models for studying the mechanism(s) of tolerance development to guanethidine and possibly other sympatholytic drugs.

Animals↗