SK&F 86466 is a novel alpha-adrenoceptor blocking drug shown in preclinical profiling to have relative selectivity for the pre- and postjunctional alpha 2-adrenoreceptor. In the present clinical study, the effects of single oral doses of 10, 25, and 50 mg SK&F 86466 on supine and stimulated circulatory and neuroendocrine function ...

The purpose of this study was to evaluate the effects of the millimicrons opioid agonist D-Ala-2-Me-Phe-4-Gly-ol enkephalin (DAGO) on catecholamine-induced arrhythmias. Arrhythmias were produced, in the rat, by continuous infusion of epinephrine until the development of fatal arrhythmias that were usually ventricular fibrillation. Intracerebroventricular (ICV) administration of DAGO, 3 nmol, ...

The effects of placebo, propranolol, and clonidine on blood pressure and blood pressure variability were examined in 14 subjects who had moderate essential hypertension. Hydrochlorothiazide was given throughout successive 4- to 5-week periods of placebo, propranolol, and clonidine administration. During each treatment period, subjects were admitted twice to the clinical ...

Since high blood pressure might be more harmful the higher it is and the more it remains above a determined critical value (140/90 mm Hg - 18.7/12.0 k Pa - in the present study), the hyperbaric impact, a measure of the total load exerted on the arterial walls and the ...

In 13 anaesthetized hens in the peak phase of their first laying year the influence of intravenously injected substance P (SP), 1-10 micrograms/animal, on oviductal pressure, duodenal pressure, blood pressure and heart rate has been studied within 5 h of oviposition. The neuropeptide induced a significant pressure increase in the ...

Epidural clonidine administration produces analgesia by a nonopiate, spinal mechanism, and offers advantages over other epidural agents for labor analgesia. To examine clonidine's acute maternal and fetal effects, the authors injected clonidine, 300 micrograms, epidurally in seven chronically prepared, near term ewes. Unlike epidural saline injection, clonidine increased maternal and ...

1. The purpose of this study was to investigate the role of an intact baroreceptor reflex mechanism in the expression of the cardiovascular response to 8-OH-DPAT and to determine whether there are any differences between the activation of central alpha 2-adrenoreceptors and 5-HT1A receptors in this respect. To this end, ...

The role of central pressor mechanisms in the maintenance of blood pressure in six hypertensive patients with angiographically proven unilateral renal artery stenosis was investigated by studying the haemodynamic and hormonal responses before and after central sympathetic blockade with clonidine. To assess the dependency of blood pressure on the direct ...

This study reports on the effects of yohimbine and clonidine on the release of adrenal and renal catecholamines (epinephrine, E; norepinephrine, NE; and dopamine, DA) in response to bilateral carotid occlusion (BCO, 3 min) in vagotomized dogs anesthetized with sodium pentobarbital. The model used allowed us to simultaneously compare adrenal ...

The effects of three kappa opioid agonists namely, bremazocine, tifluadom and U-50,488H were studied on blood pressure and heart rate in urethane-anesthetized normal and bilateral adrenal demedullated rats. Bremazocine (0.2, 0.4 and 0.6 mg/kg i.v.) produced a dose-dependent decrease in heart rate, while only 0.4 mg/kg bremazocine produced marked hypotension. ...

Blood pressure and heart rate were recorded continuously in methoxyflurane anaesthetized dogs. Amitraz (i.v.) caused a dose-dependent rise in blood pressure with a fall in heart rate at lower doses. Pressor responses to amitraz were reduced by phentolamine and slightly enhanced by atropine and hexamethonium, while bradycardia was reduced by ...

The putative neurotransmitters, L-glutamate and norepinephrine were microinjected (50nl) unilaterally into the paraventricular nucleus of pentobarbital-anesthetized rats. L-glutamate (0.5M) elicited a rise in plasma ACTH, vasopressin, and oxytocin and a profound drop in heart rate that was accompanied by no significant change in blood pressure. The bradycardia was blocked by ...

The alpha-adrenoceptor agonist ST-1059 (2-amino-1-(2,5-dimethoxyphenyl) ethanol), the alpha 1-adrenoceptor agonist methoxamine, the alpha 2-adrenoceptor agonist clonidine and a nonselective alpha-adrenoceptor agonist norepinephrine, all increase cardiac output and dose-dependently increase arterial blood pressure in spinally anesthetized ganglion-blocked dogs. The increase in cardiac output may be the result of an increased venous ...

The effect of drug-induced hypertension and hypotension on neurotransmitter metabolism in the locus coeruleus (LC) of urethane anesthetized rats was studied using in vivo electrochemical methods. Peaks were seen at +0.15 V and +0.28 V. Studies with alpha-methylparatyrosine, fusaric acid and pargyline showed the first peak was produced by extracellular ...

1. In conscious rabbits, intravenous morphine (3 mg/kg) caused hypertension, bradycardia, hyperglycaemia and sedation. These changes were accompanied by large increases in plasma adrenaline and smaller increases in plasma noradrenaline. 2. These effects of morphine were prevented by intravenous naloxone, demonstrating their dependence on stimulation of opiate receptors. 3. Pretreatment ...

Forty healthy patients (ASA class 1) of both sexes, aged between 20 and 45 years, undergoing routine surgical procedures were included in this double-blind randomized study. They were divided into two groups of 20 each. Patients in group A received no pretreatment, while patients in group B received oral clonidine ...

1. The involvement of alpha 2-adrenoceptors in a capsaicin-induced depressor reflex in the rat has been investigated. 2. The reflex fall in blood pressure following an intra-arterial injection of capsaicin was partially blocked by an intrathecal infusion of clonidine (1 microgram) at the spinal cord level L4-L5, an effect which ...

Clonidine can produce symptomatic sinus bradycardia or atrioventricular (AV) block in some patients. Electrophysiologic studies have been performed after intravenous clonidine in patients showing such side effects; these have demonstrated variable depression of sinus and AV nodal function. We have evaluated the electrophysiologic and hemodynamic effects of chronic oral treatment ...

A single-dose comparative evaluation in young normotensive men of the plasma concentrations and alpha-adrenoceptor antagonism after conventional prazosin and a new slow-release formulation (Oros) is described. Whereas conventional prazosin (2 mg) produced a maximum reduction in erect blood pressure at 3 hours (80/46 mm Hg compared with 110/65 mm Hg ...

The effects of clonidine on intraocular pressure and perioperative cardiovascular variables were studied by a randomized double blind design in 80 elderly patients (ASA physical status I-III) scheduled for elective ophthalmic surgery under general anesthesia (GA) and local anesthesia (LA). Group 1 (n = 40), the control group, received diazepam ...

The purpose of our study was to determine whether clonidine exerts its centrally mediated hypotensive action at three sites that influence arterial pressure located in the medulla, specifically associated with the intermediate area of the ventrolateral medulla. The "intermediate area" lies approximately 1.5 mm caudal to the border of the ...

The effects of infusion of alpha-adrenoceptor agonists on blood pressure, pressor responses to bolus doses of agonists and to platelet aggregation were examined in rabbits with perinephritis hypertension and in sham-operated controls. Pressor responses to bolus doses and infusions of phenylephrine, an alpha 1-selective agonist, were greater in hypertensive rabbits. ...

We report the case of a 46-year-old woman who took approximately 8 mg of clonidine in a suicidal gesture. She arrived in the emergency department 45 min after the overdose with severe hypertension and an altered mental status. Nitroprusside, which is the drug of choice for treating this "paradoxical hypertension," ...

Clonidine is a centrally acting antihypertensive drug that acts in vivo at both alpha 1- and alpha 2-adrenoceptor sites, whereas rilmenidine (S 3341) is more selective for alpha 2 adrenoceptors. The present study compared the effects of continuous 10-day infusions of clonidine (5 micrograms/kg/hour) with those of rilmenidine (100 micrograms/kg/hour) ...

The clonidine transdermal therapeutic system (TTS) is a cutaneous delivery device which provides therapeutically effective doses of clonidine at a constant rate over 7 days. In clinical trials it reduces blood pressure in patients with mild to moderate hypertension as effectively as oral clonidine but with greater stability of blood ...

In the rat, the continuous intrathecal (i.t.) infusion of clonidine (0.4 microgram/hr) significantly increased the tail-flick latency (TF) and the threshold for paw pressure (PP) withdrawal for 5 days and decreased the systolic blood pressure (up to 24 mm Hg) for 7 days. The antinociceptive effect of continuous intrathecal infusion ...

Central alpha-2-adrenoceptor function was studied in seven withdrawing alcoholics and compared with seven normal controls using the clonidine challenge test. The alcoholic group had significantly elevated basal levels of blood pressure and plasma 3-methoxy-4-hydroxy-phenyl glycol. The percentage of fall in blood pressure produced by clonidine was blunted in the alcoholics. ...

This study examined a possible peripheral site of action of opiates in the modulation of the response to noxious pressure on inflamed paws. Rats received an injection of Mycobacterium butyricum suspension into one hindpaw which resulted in an ipsilateral inflammatory response (swelling) and decreased threshold to noxious pressure within 1-2 ...

The effects of clonidine or relaxation therapy were determined in two separate groups of patients with primary hypertension. Ten patients were treated with clonidine monotherapy for 3 months. There were concurrent reductions of blood pressure, plasma and CSF norepinephrine, all p less than 0.01. The changes of blood pressure and ...

The effect of clonidine on amitriptyline-induced cardiotoxicity was investigated in an experimental rat mode. A continuous infusion of amitriptyline (30 mg/kg/h) was given until the animal died, usually within 2 hours. Fifteen minutes after starting the amitriptyline infusion, 50 micrograms/kg of clonidine was given intravenously over five minutes. This led ...

Evidence from studies in both animals and in tetraplegics with complete cervical spinal cord transection and preganglionic lesion, indicates that clonidine lowers blood pressure predominantly by a centrally mediated action. We have investigated the haemodynamic basis of this action and performed additional studies in patients with unilateral brachial plexus injury ...

In the present study, immunopharmacological effects of clonidine-TTS on allergic contact dermatitis (ACD) to non-related, established contact sensitizers were investigated in guinea pigs. First, to evaluate the hypotensive effect of clonidine-TTS in guinea pigs, intra-arterial blood pressure was recorded. After 4 days of treatment with one (or two) TTS per ...

Serotonin enhances (amplifies) the vasoconstrictor effect of norepinephrine not only on isolated large blood vessels and isolated perfused vascular beds but also in vivo. This amplification can be observed with endogenous serotonin released from aggregating platelets and with endogenous norepinephrine released from the adrenergic nerves in the blood vessel wall. ...

Spontaneously hypertensive (SH) rats were trained to discriminate the effects of saline injection from the interoceptive stimuli associated with the blood-pressure-reducing effect of clonidine (0.02 mg/kg, IP) in a drug discrimination procedure. Anise/ethanol and ethanol odors were then systematically paired with clonidine and saline treatment, respectively, outside the drug discrimination ...

The effects of prazosin, clonidine, and indoramin on central and regional hemodynamic parameters and left ventricular performance were analyzed in a congestive heart failure population to compare the pharmacodynamic responses to different levels of alpha-adrenergic interruption in this condition. The sympathetic nervous system is blocked at the peripheral alpha1-receptor by ...

Responses to intravenous clonidine, a possible central noradrenergic probe, were examined in patients with depression before and after treatment with clorgiline, a selective monoamine oxidase type A inhibitor. Pulse rate, mean arterial blood pressure, plasma norepinephrine, 3-methoxy-4-hydroxyphenylglycol, and growth hormone were measured. Clorgiline treatment (2.5 to 10 mg/day) produced a ...

In spite of the fact that plasma catecholamine levels, baroreflex activity, and hemodynamic pattern significantly change with age and drugs whose action is mediated via the sympathetic nervous system might be expected to cause different effects, the limited available data suggest that both alpha-methyldopa and clonidine lower blood pressure to ...

The major purpose of our study was to determine whether urapidil acts in the central nervous system (CNS) to lower arterial blood pressure. Once demonstrating a CNS antihypertensive action of urapidil we further set out to determine: (1) the relative role of a CNS antihypertensive action to the total antihypertensive ...

The efficacy and patient acceptance of transdermal clonidine applied once a week were assessed in 62 mild hypertensives previously controlled on a diuretic and/or beta-blocker in a general practice setting involving 18 general practitioners. Patients underwent 3-5 week wash-out period and those patients whose mean seated diastolic blood pressure returned ...

In vivo electrochemical recordings of the metabolism of catecholamines were obtained in the caudal ventrolateral medulla in anesthetized rats submitted to various experimental changes in systemic arterial pressure. Hypertension induced with phenylephrine and reversal of hypovolemia decreased the catechol metabolic activity. In contrast, controlled or hypovolemic hypotension, induced respectively with ...

We studied in 32 patients on maintenance hemodialysis (duration of treatment 6 to 133 months) whether duration of dialysis treatment affects blood pressure, plasma noradrenaline levels and alpha 2-adrenoceptor density (assessed in platelet membranes by 3H-yohimbine binding). Plasma noradrenaline levels were a significant inverse correlation to platelet alpha 2-adrenoceptor density. ...

Yohimbine, an alpha 2-adrenergic receptor antagonist that increases noradrenergic function, was administered to 16 healthy subjects and 18 drug-free schizophrenic patients with (n = 10) and without (n = 8) tardive dyskinesia (TD). Outcome measures of this double-blind, placebo-controlled study included changes in behavior, plasma 3-methoxy-4-hydroxy-phenylglycol (MHPG) level, blood pressure, ...

The involvement of cholinergic mechanisms in the central cardiovascular effects of a dihydropyridine, nicardipine, was investigated in pentobarbital-anaesthetized normotensive dogs. Nicardipine (1 microgram/kg) injected intracisternally (i.c.) induced a rise in both blood pressure and heart rate. This induced hypertension was suppressed by pretreatment with intravenous (i.v.) atropine or i.c. methylatropine ...

We have previously reported an increased prevalence of elevated blood pressure in Hispanic adolescent males. The pressure elevation did not correlate with weight. In this study, we evaluated the response to antihypertensive therapy of eight adolescent Hispanic males found to have elevated pressure during high school screening. All patients were ...

The acute intrathecal (i.t.) injection of 50, 100, 200, 250 and 300 nmol of oxymetazoline produced dose-dependent antinociception in rats assessed by tail flick and paw pressure tests. Significant antinociception was observed with all doses of oxymetazoline except 50 nmol in the paw pressure test. The ED50 values for i.t. ...

The effects of yohimbine, an alpha 2-adrenergic receptor antagonist, on anxiety, blood pressure, heart rate, and plasma levels of the norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) and cortisol were determined in 20 healthy subjects and 68 patients who had agoraphobia with panic attacks or panic disorder. Yohimbine produced panic attacks meeting DSM-III ...

To assess adrenal medulla activity in states of hyperfunction, a single 0.3 mg oral dose of clonidine hydrochloride (Catapres) was given to twelve patients with varying evidence of familial adrenal medullary hyperplasia and pheochromocytomas from kindreds with Multiple Endocrine Neoplasia type 2 syndrome (MEN-2), seven patients with sporadic pheochromocytomas and ...

The effects of an alpha 2 adrenoceptor blocker, yohimbine, and an alpha 1 adrenoceptor blocker, phenoxybenzamine, and the central alpha 2 adrenoceptor agonist, clonidine, on changes in arterial blood pressure and heart rate were studied during fatiguing muscular contractions to determine whether an adrenergic-opioidergic system might be involved in the ...

Thoracic preganglionic sympathetic nerve activity, blood pressure, heart rate and femoral arterial conductance were recorded in anaesthetised, paralysed cats. Cumulative dose-response curves were constructed for 8-OH-DPAT, ipsapirone and clonidine. All three drugs caused dose-related falls in blood pressure which were associated with minimal changes in femoral arterial conductance. However, 8-OH-DPAT ...

Experiments were carried out in the dog by the use of experimental procedure which permits to assess independently changes in uretheral peristaltic frequency, bolus volume and intraluminal pressure and flow volume in order to characterize alpha-adrenoceptor subtypes involved in regulation of ureteral urine transport. Norepinephrine caused an increase in ureteral ...