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 37 records · Page 2Linked to original sources
PubMed1985

Mechanisms underlying changes in the contents of neuropeptide Y in cardiovascular nerves and adrenal gland induced by sympatholytic drugs.

Neuropeptide Y (NPY) is a recently isolated vasoactive peptide, which is present, together with catecholamines, in sympathetic nerves and in the adrenal medulla. In the present study, we report that pretreatment with sympatholytic agents influences the tissue levels of NPY-like immunoreactivity (NPY-LI) in the guinea-pig. Thus, 24 h after reserpine not only noradrenaline (NA), but also NPY-LI, was depleted in the heart, spleen and the adrenal gland. The levels of NPY-LI in the vas deferens and stellate ganglia, however, were unaffected by reserpine in spite of marked depletions of NA. The reserpine-induced depletion of NPY-LI was probably caused by enhanced nerve-impulse flow and subsequent release from cardiovascular nerves in excess of resupply, since it could be prevented by the ganglionic-blocking agent chlorisondamine. Long-term (6 days) treatment with chlorisondamine reduced the levels of NPY-LI in the stellate ganglion. Short-term treatment (48 h) with guanethidine partially prevented the reserpine-induced depletion of NPY-LI, probably due to inhibition of NPY release. Long-term guanethidine treatment depleted not only NA, but also NPY-LI from the spleen. Pretreatment with the alpha-receptor antagonist phenoxybenzamine did not influence the NA levels but reduced the content of NPY-LI in the spleen via a mechanism that was dependent on intact ganglionic transmission. Since NPY has several cardiovascular actions, changes in NPY mechanisms may contribute to the pharmacological and therapeutical effects of sympatholytic agents.

Adrenal Glands↗
PubMed1991

Role of ventrolateral medulla in sympatholytic effect of 8-OHDPAT in rats.

In halothane-anesthetized, paralyzed, and artificially ventilated rats, the putative 5-hydroxytryptamine1A receptor agonist 8-OHDPAT (13.1 micrograms/kg iv) produced hypotension (-14.6 +/- 1.3 mmHg, n = 35), reduced lumbar sympathetic nerve discharge (SND, -17.8%, n = 35), and slowed the discharge rate of sympathoexcitatory neurons recorded in the rostroventrolateral medulla (RVLM, -17.6%, n = 20). The gain of the baroreflex was unaffected by the drug, but SND and RVLM unit discharges were silenced at significantly reduced levels of mean arterial pressure (MAP; 153 vs. 171 mmHg for SND, 155 vs. 172 mmHg for RVLM cells). Subsequent intravenous administration of the alpha 2-adrenergic receptor agonist clonidine (5.3 micrograms/kg) produced an additional decrease in MAP (-21.2 +/- 1.9 mmHg, n = 24) and SND (-24%, n = 24), Bilateral microinjections of 8-OHDPAT into the RVLM (1 nmol/side, n = 9) or into the raphe pallidus-obscurus (2 injections of 1 nmol each, n = 7) also produced hypotension (-22.9 +/- 3.2 and -14.4 +/- 2.8 mmHg, respectively) and sympathoinhibition (-39.1 and -24.6%, respectively). Bilateral microinjection into RVLM of the alpha 2-adrenergic antagonists idazoxan (16 nmol/side, n = 6) or rauwolscine (2 nmol/side, n = 6) attenuated the sympatholytic effect of both 8-OHDPAT (13.1 micrograms/kg, iv) and clonidine (5.3 micrograms/kg iv). These results suggest that 8-OHDPAT may exert a portion of its central sympatholytic effect by activating alpha 2-adrenergic receptors in the rostroventral medulla.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1976

Angina in hypertensive patients. With particular reference to the negative chronotropic effects of sympatholytic therapy.

There was no significant difference in the blood pressure and heart rate response of hypertensive patients with and without angina to standardised exercise on a treadmill before and after anti-hypertensive treatment. There was no improvement in exercise tolerance in the hypertensive patients with angina treated with bethanidine, debrisoquine or guanethidine despite a reduction of resting and exercise heart rates after treatment. The negative chronotropic effect of these sympatholytic drugs was less than that of oxprenolol or propranolol, but the hypotensive response was greater. Both of these beta-receptor blocking drug produced an an improvement in exercise tolerance in patients with angina either alone or in combination with other hypotensive therapy. The best control of blood pressure and angina was often achieved by a combination of a sympatholytic drug and beta-receptor blocking drug. In hypertensive patients treated for several years, angina at presentation was occassionally reduced by reduction of blood pressure. Later onset of angina appeared to be unrelated to control of hypertension but to be due to coincidental coronary occlusion. There was no evidence that myocardial infarction was precipitated by postural or exercise hypotension although these effects occasionally precipitated angina.

Adrenergic beta-Antagonists↗
PubMed1981

Sympatholytic effect on striated urethral sphincter. A peripheral or central nervous system effect?

Effects of intravenous administration of sympatholytic drugs on urethral pressure and electromyographic activity from urethral and anal sphincter, were investigated in five normal women. Clonidine (Catapresan), which easily passes the blood brain barrier, resulted in a pronounced decrease in urethral pressure and electromyographic activity from both sphincters. Phentolamine (Regitine), which does not pass the blood brain barrier, also lowered urethral pressure but had no effect on electromyographic activity from the sphincters. Neither drug depressed reflex induced increase in urethral pressure and sphincter activity during bladder filling or during voluntary contraction of the pelvic floor muscles. Phenoxybenzamine administration to one normal female had the same effect as clonidine. It is suggested that part of the clinical effect on voiding disorders seen after treatment with sympatholytic drugs passing the blood brain barrier (e.g. phenoxybenzamine) might be due to an effect on the central part of the striated urethral sphincter innervation.

Adult↗
PubMed1993

Thermal biofeedback as an effective substitute for sympatholytic medication in moderate hypertension: a failure to replicate.

Thirty-three moderate hypertensives were converted to a 2-drug regimen of metoprolol and diuretic and BPs stabilized at a well-controlled level. They then completed one of three conditions over an 8-week interval: (I) 16 sessions of TBF (hand and foot warming); (II) 16 sessions of frontal EMG-BF; (III) regular home monitoring of BP. Attempts were then made to withdraw the patients from the sympatholytic medication. Those successfully withdrawn were followed up for one year. There were no significant advantages for TBF over the other two conditions in the short term or with long-term follow-up. Only 27% of treated patients (including Condition III failures who were remedicated and treated with TBF) were successfully off of the sympatholytic at a one-year follow-up. The generally poor results on clinical outcome were confirmed by clinic BPs, home BPs by patients, and 24-hour ambulatory BPs.

Biofeedback, Psychology↗
PubMed1991

Sympatholytic action of yohimbine mediated by 5-HT1A receptors.

The present study determined the mechanism by which yohimbine inhibits sympathetic nerve activity in the anesthetized cat. Low i.v. doses of yohimbine increased inferior cardiac nerve discharge as a result of the alpha 2-adrenoceptor antagonist properties of the drug. Higher doses of yohimbine (0.8-1.6 mg/kg) inhibited sympathetic nerve discharge. The inhibition of nerve activity was reversed by i.v. administration of the 5HT1A receptor antagonist spiperone. Similarly we have previously observed spiperone reversal of the sympatholytic effects of the 5-HT1A agonist 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin) but failed to affect nerve activity when given alone. Spiperone failed to reverse the sympatholytic effect of clonidine. These data indicate that high doses of yohimbine inhibit sympathetic nerve activity via a 5HT1A agonist action.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1996

The sedative and sympatholytic effects of oral tizanidine in healthy volunteers.

Tizanidine, an imidazoline derivative with alpha 2-receptor-mediated central muscle relaxant activity, is in widespread clinical use for the treatment of spasticity. To evaluate its possible role in anesthesia we assessed the sedative and sympatholytic effects of orally administered tizanidine in a double-blind, placebo-controlled, randomized, cross-over study in six healthy male volunteers. Three different doses of tizanidine (4, 8, and 12 mg) were tested and compared to clonidine 150 micrograms. The sedative and sympatholytic effects of tizanidine 12 mg were comparable in magnitude to those of clonidine 150 micrograms, but the effects of clonidine were longer lasting. Similarly, the observed decreases in arterial blood pressure (diastolic, 13% and 19%; systolic, 10% and 8% for tizanidine and clonidine, respectively) and salivation were comparable in magnitude but of shorter duration after tizanidine 12 mg than after clonidine. Clonidine and tizanidine 12 mg had also similar effects on the secretion of growth hormone. Our results indicate that the effects of a single 12-mg oral dose of tizanidine resemble those of 150 micrograms oral clonidine, but are of shorter duration. Tizanidine may thus be a useful alternative to clonidine as an orally active, short-acting alpha 2-adrenoceptor agonist in the perioperative period.

Administration, Oral↗
PubMed2003

5-HT1A receptor agonist 8-OH-DPAT acts in the hindbrain to reverse the sympatholytic response to severe hemorrhage.

Central administration of serotonergic 5-HT1A receptor agonists delays the reflex sympatholytic response to severe hemorrhage in conscious rats. To determine the region where 5-HT1A receptor agonists act to mediate this response, recovery of mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) was compared in hemorrhaged rats after injection of the selective 5-HT1A agonist, (+)-8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), in various regions of the cerebroventricular system or the systemic circulation. Three minutes after injection of 8-OH-DPAT (48 nmol/kg), MAP and RSNA were higher in hemorrhaged rats given drug in the fourth ventricle (94 +/- 5 mmHg, 82 +/- 18% of baseline) or the systemic circulation (90 +/- 4 mmHg, 113 +/- 15% of baseline) than in rats given drug in the Aqueduct of Sylvius (63 +/- 4 mmHg, 27 +/- 11% of baseline), the lateral ventricle (42 +/- 3 mmHg, -8 +/- 18% of baseline), or in rats given saline in various brain regions (47 +/- 5 mmHg, -42 +/- 10% of baseline). A lower-dose injection of 8-OH-DPAT (10 nmol/kg) also accelerated the recovery of MAP and RSNA in hemorrhaged rats when given in the fourth ventricle (94 +/- 26 mmHg, 72 +/- 33% of baseline 3 min after injection) but not the systemic circulation (46 +/- 4 mmHg, -25 +/- 30% of baseline). These data indicate that 8-OH-DPAT acts on receptors in the hindbrain to reverse the sympatholytic response to hemorrhage in conscious rats.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMedDate not supplied

[Rilmenidine sympatholytic activity preserves mental and orthostatic sympathetic response and epinephrine secretion].

BACKGROUND: Heightened central sympathetic nervous outflow is common in essential hypertension, contributing to hypertension development and perhaps also to complications. Acute sympathetic nervous activation is a proven trigger for adverse cardiovascular events. Accordingly, antihypertensive drugs inhibiting sympathetic outflow represent a theoretically attractive therapeutic option. OBJECTIVES: To study the sympatholytic and blood pressure lowering activity of the imidazoline binding agent rilmenidine at rest and during reflex sympathetic activation. DESIGN AND METHODS: The HERA study (Hyperium Effect on the sympathetic Reflex activation and Adrenaline) is a randomised, double-blind, 6-week cross-over trial, with a 1-week placebo run-in period, two 2-week active treatment intervals (rilmenidine 1 mg bid, placebo) and intervening one week placebo wash-out. In 15 hypertensive patients, noradrenaline and adrenaline plasma kinetics and intra-arterial blood pressure measurements were performed at rest, after mental stress (difficult mental arithmetic) and during head-up tilting, at the end of the 2-week dosing periods. RESULTS: The noradrenaline spillover rate, indicative of whole body sympathetic activity, was reduced 35% by rilmenidine at rest (p<0.01) and remained significantly lower during mental stress and tilting, although the increases in noradrenaline spillover with both stimuli were preserved. The effects on intraarterial blood pressure ran in parallel, a fall in supine resting pressure, but no reduction in BP rise during mental stress and a lack of fall in BP with tilting. On placebo, adrenaline secretion was 162 +/- 27 ng/min (mean, SE) at rest, increased by 77 +/- 42 ng/min with mental stress (p=0.019) and was unchanged with tilting. Rilmenidine left adrenaline secretion untouched under all conditions. CONCLUSIONS: This study confirms a sympatholytic effect of rilmenidine during supine rest but demonstrates that sympathetic responses during mental stress and tilting are preserved, the latter underlying a perhaps surprising absence of postural hypotension on the drug. The absence of suppression of reflexive sympathetic responses contrasts with the effects of rilmenidine in experimental animals, and emphasises the previously demonstrated unique importance in humans of suprabulbar noradrenergic neuronal projections from the brainstem, which are inhibited by imidazoline binding agents, in regulating tonic sympathetic activity in essential hypertension. Sympathetic nervous inhibition with rilmenidine contrasted with an absence of suppression of the secretion of adrenaline affirming that here, as elsewhere, sympathetic nervous and adrenal medullary function can be disconnected.

Adult↗
PubMed1990

[Cardiovascular reactivity to isometric stress in patients with stable and borderline hypertension and in normotensive subjects. Effects of alpha sympatholytics and beta blocking agents].

Aim of the study was to evaluate blood pressure (BP) and heart rate (HR) variability during isometric handgrip test (IHT) in 20 ambulant non-obese male adults affected by sustained hypertension (SH) WHO I and II, 20 borderline hypertensive (BH) and 20 normotensives (C) of comparable sex, age and BMI. SBP and DBP were assessed by "Random Zero" sphygmomanometer, HR by ECG registration. IHT was performed at 30% of maximal effort for 3 min. IHT was carried out: 1) after 7 days placebo, 2) after 7 days propranolol treatment (80 mg/day) and, following 10 days wash-out, 3) after 7 days prazosin treatment (0.5 mg/day). After placebo IHT caused increases of SBP, DBP and HR values insignificantly different in the 3 groups. After propranolol IHT induced significantly more elevated SBP and DBP increases in SH than in BH or in C. These increases were significantly more elevated in comparison with those observed, in advance, in the same group of SH subjects after placebo. After prazosin treatment SBP increase induced by IHT was, on the contrary, significantly more elevated in BH than in SH or in C. This increase is more significant in comparison with that observed in the same BH group after placebo treatment. As for DBP variations induced by IHT after alpha sympatholytic therapy we have observed that SH subjects show significantly lesser diastolic variations as compared with those obtained in BH or in C groups after this treatment. In conclusion, enhanced IHT induced SBP elevation after propranolol and dampened DBP reactivity after prazosin suggest an overriding alpha stimulation in SH subjects. SBP hyperreactivity induced by IHT after alpha sympatholytic treatment and DBP hyporeactivity after betablockers emphasize the role of beta stimulation in BH individuals. Inhibition of BP reactivity to IHT in C after prazosin suggest that this one is mediated by alpha adrenergic receptors.

Adult↗
PubMed1980

[New beta-sympatholytic agents. Synthesis and pharmacological activity of isomeric benzthiazole and benzoxazole derivates (author's transl)].

The synthesis and comparative pharmacological studies concerning structure-activity relationship of new benzothiazole, benzisothiazole, benzoxazole, and benisoxazole derivatives with beta-sympatholytic activity are reported. Most of the 4-benzisothiazole derivatives studied strongly act on cardiac beta 1-receptors in rats in situ (2.6-8.3 times propranolol). On the other hand derivatives of 4-benzisoxazole and 5-benzisothiazole are less potent. A strong decrease in activity was observed going from the benzisothiazoles and benzisoxazoles to the isomeric benzthiazoles and benzoxazoles. The active substances also block vascular beta 2-receptors. In the most cases they have little intrinsic adrenergic activity. The observed tendency concerning beta 1-selectivity in rats could not be confirmed in cats. The most potent 4-benzisothiazole derivatives in rats show also - beside some minor differences - very good beta-sympatholytic activity in cats after i.v. as well as after i.d. administration. Similar to the results in rats and cats the 4-(2-hydroxy-3-isopropylamino-propoxy)-1,2-benzisothiazole (LU 24329) was found to possess a high activity in conscious dogs by oral or i.v. application. Both in dogs (i.v.) and in isolated perfused guinea pig hearts LU 24329 is eleven times more active than propranolol in blocking beta 1-receptors. A negative inotropic effect as an expression of non-specific membrane-stabilizing action of LU 24329 is also demonstrated in guinea pig hearts. The effective concentration is 4650 times higher than that effective on beta 1-adrenoceptors. The active compounds have a moderate acute toxicity. The LD50 values in mice after i.p. administration are ranging from 55-174% of the propranolol toxicity.

Adrenergic beta-Antagonists↗
PubMed1964

SYMPATHOLYTIC DRUGS AND HYPERLIPAEMIA INDUCED IN RATS BY INTRAPERITONEAL INJECTIONS OF SURFACE-ACTIVE AGENT.

Hyperlipaemia and hypercholesterolaemia were induced in white rats by intraperitoneal injections of tyloxapol. Various sympatholytics and adrenolytics, including blocking agents of beta-receptors, were given simultaneously with tyloxapol. Bretylium tosylate prevented the increase in the serum levels of esterified fatty acids and cholesterol caused by tyloxapol. Phentolamine decreased the enhancement by tyloxapol of cholesterol and total lipid concentrations in the serum. Guanethidine and phenoxybenzamine reduced the increase in the concentration of esterified fatty acids, whereas dichloroisoprenaline insignificantly increased the tyloxapol-induced hyperlipaemia. A small dose of pronethalol slightly increased the esterified fatty acid level in tyloxapol-treated animals; a large dose significantly decreased the serum cholesterol concentration.

Bretylium Compounds↗
PubMed1996

Sympathetic nervous system in salt-sensitive and obese hypertension: amelioration of multiple abnormalities by a central sympatholytic agent.

Excess activity of the sympathetic nervous system (SNS) is linked to human obese hypertension and to salt-sensitive hypertension. Paradoxically, reduced SNS activity has been implicated as a contributor to obesity, particularly in animal models, and salt loading usually inhibits SNS activity. We have investigated the relationship between SNS activity, diet, and hypertension in the obese spontaneously hypertensive rat (SHROB), a model with a recessive obesity trait superimposed on a hypertensive background with multiple metabolic abnormalities resembling human syndrome X. We examined the role of SNS overactivity in the adverse impact of excess dietary salt and the possible beneficial effects of sympatholytic therapy. Mean blood pressure (MBP) was increased in SHROB and SHR fed a 4% NaCl diet. The pressor effect of dietary salt was abolished by ganglionic blockade, suggesting that increased SNS activity contributed to the pressor effect of the high-salt diet. Moxonidine, a second-generation central antihypertensive, controlled hypertension in both SHROB and SHR. Kidney damage in SHROB was accelerated by dietary salt and was reduced by moxonidine. Moxonidine elicited progressive weight loss in SHROB but not in SHR. Food intake in SHROB was reduced to the level of lean SHR. SHROB and SHR treated with moxonidine showed improved glucose tolerance. Additionally, SHROB showed reduced levels of triglycerides, cholesterol, and insulin following moxonidine therapy. Inhibition of the SNS, as with moxonidine therapy, may ameliorate multiple abnormalities and have therapeutic advantages in obese hypertensive syndromes.

Animals↗
PubMed1976

The influence of some sympatholytic, parasympatholytic and serotonin-synthesis-inhibiting agents on the ultrastructure of the rabbit pineal organ.

The influence of certain drugs on the ultrastructure of rabbit pinealocytes was studied. The results obtained after administration of p-chlorophenylalanine and p-chloroamphetamine support the hypothesis proposed earlier that the smooth endoplasmic reticulum in the light pinealocytes is involved in indoleamine synthesis. The administration of either one of the sympatholytic agents, 6-hydroxydopamine or alpha-methyl-p-tyrosine, induced typical fine structural changes corresponding to those observed after surgical sympathectomy.

5-Hydroxytryptophan↗
PubMed1995

Sympatholytic effect of clonidine depends on the respiratory phase in rat splanchnic nerve.

Peri-event averaging of the sympathetic nerve discharge was done to measure the magnitude of the sympatholytic effect of the anti-hypertensive drug clonidine during three different phases of the respiratory cycle (inspiration, I; postinspiration, post-I; late expiration, pre-I). Arterial pressure (AP) and discharges of splanchnic sympathetic (SND) and phrenic nerves (PND, onset used for peri-event averaging) were recorded in urethane-anesthetized, vagotomized, aortic deafferentated, paralyzed and artificially ventilated Sprague-Dawley rats (n = 7). During control periods (mean AP 106 +/- 10 mmHg) SND was distributed equally throughout the three selected respiratory periods, though two brief peaks were noted during the I and post-I periods. Low doses of clonidine (15-30 micrograms/kg i.v.) produced brief hypertension (< 30 s, 150 +/- 9 mmHg at peak) followed by moderate hypotension (89 +/- 3 mmHg) and a reduction in mean SND (-63 +/- 11% from control value). High doses of clonidine (200-250 micrograms/kg i.v.) produced sustained hypertension (> 10 min, 173 +/- 3 mmHg) and silence of SND. During this sustained hypertension, lowering AP by i.v. nitroprusside retrieved a component of SND that was barosensitive but insensitive to clonidine. During those hypotensive periods (spontaneous after a low dose of clonidine, and induced by nitroprusside after a high dose of clonidine), SND was most attenuated during the pre-I period and least during the I period. The I component of SND was significantly less attenuated than the post-I component by clonidine and, in most cases (6 out of 7), SND showed a single inspiratory peak following clonidine administration. It is concluded that (i) the pre-I component of SND is the most sensitive to clonidine and (ii) the I component of SND is the most resistant to the drug.

Action Potentials↗
PubMed1993

Effects of sympathomimetic and sympatholytic drugs on exercise performance.

This article has presented information on the importance of the sympathetic nervous system in the response to exercise. The authors have reviewed the very limited information on the effects of sympathomimetic and sympatholytic drugs on exercise performance in the horse. Most of these drugs are specifically prohibited under the rules of racing, and they have significant side effects that either decrease performance or make their use dangerous to both the horse and horse-man. Additionally, all of these drugs or their metabolites are readily detected by current drug testing protocols. Further information is needed to expand our knowledge of how each of these substances affects the health of the equine athlete.

Animals↗
PubMed1986

7-(Trifluoromethyl)-4-aminoquinoline hypotensives: novel peripheral sympatholytics.

A family of 7-(trifluoromethyl)-4-aminoquinolines that are hypotensive agents and that act by a novel sympatholytic mechanism is described. Structure-activity relationships in this series have been elucidated. Some of the more potent hypotensives were evaluated for safety in the mouse. A candidate, 1-[(4-fluorophenyl)sulfonyl]-4-[4-[[7-(trifluoromethyl)-4- quinolinyl]amino]benzoyl]piperazine hydrochloride (losulazine hydrochloride) has been selected for clinical development. Losulazine hydrochloride is a hypotensive agent in the rat, cat, and dog. At acute effective hypotensive doses, it does not block the response of the sympathetic nervous system to stimuli. Both animal pharmacology and clinical experience suggest that losulazine hydrochloride may be free of the clinically limiting side effects that often plague compounds that decrease blood pressure by interfering with autonomic neurogenic function.

Aminoquinolines↗
PubMed1981

Influence of sympatholytic drugs on the cardiovascular response to isometric exercise.

1. The effects of single oral doses of various sympatholytic drugs on the heart rate and blood pressure increases during isometric handgrip contraction were studied in six healthy subjects. 2. Bethanidine reduced both the systolic and diastolic increases in pressure. Clonidine reduced the systolic but not the diastolic increase. Oxprenolol alone or in combination with phentolamine or phenyoxybenzamine failed to influence the pressor response. 3. The increase in systemic blood pressure associated with sustained contraction of voluntary muscle appears to be relatively resistant to acute sympathetic adrenoreceptor blockade in man.

Adult↗