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PubMed1986

Norepinephrine with its precursors and their antagonists haloperidol and phentolamine interact with dye free radicals in opposite ways.

In the reactions with dye free radicals, catecholamines exhibited reversible electron donor and acceptor properties with the effectiveness increasing from tyrosine to norepinephrine. The physiological antagonists haloperidol and phentolamine showed opposite patterns of behaviour in the same reactions, changing their properties as acceptors to electron donors. The regularity observed is similar to that demonstrated earlier by a variety of Na+ and Ca2+ channel modulators.

Coloring Agents↗
PubMed1977

Phentolamine prevents the somatostatin-mediated inhibition of pancreatic glucagon secretion.

This study was undertaken to assess the role of alpha-adrenergic receptors in the somatostatin-mediated inhibition of pancreatic glucagon secretion. In dogs, somatostatin inhibited the pancreatico-duodenal vein output of glucagon. During an infusion of the alpha-adrenergic blocking agent phentolamine, somatostatin did not significantly inhibit the output of glucagon. Thus, alpha-adrenergic mechanisms appear to influence the ability of somatostatin to decrease pancreatic glucagon secretion.

Animals↗
PubMed1988

Phentolamine stimulates insulin release and glucose clearance and suppresses food ingestion.

In Experiment One, phentolamine (PTA), an alpha-adrenergic blocker, was injected in rats at doses of 0, 50, 100, 200, and 300 micrograms/kg following a 4-hr fast. Measurement of food intake 1-hr postinjection revealed that 300 micrograms/kg PTA reduced food intake. Experiment Two evaluated the potential aversiveness of 300 micrograms/kg PTA. Four-hour fasted rats were adapted to a milk diet as the only food source during a 1-hr intake measurement period. After the 15-day adaptation period, three separate groups of animals (n = 8 per group) received the milk with cherry flavoring added and infections of either 1% body weight 0.9 NaCl, isosmotic LiCl or 300 micrograms/kg PTA. Only those subjects that had received LiCl injections developed a reliable aversion to the cherry-flavored milk. The final experiments subdivided the 1-hr feeding period into three 20-min segments and, in separate animals, food intake or plasma insulin and glucose changes were assessed. The animals were assigned to one of two groups receiving either 300 micrograms/kg PTA or equivolume 0.9% NaCl. PTA-injected subjects showed an immediate modest enhancement of insulin release during the first 20-min feeding segment following injection, compared to controls, while blood glucose levels decreased but never differed reliably between groups. Food intake was reliably suppressed in the second and third 20-min segments for the PTA-injected rats. We advance that PTA by enhancing glucose clearance may be reducing ingestion.

Animals↗
PubMed1989

Intracavernous injections of papaverine and phentolamine: correlation with penile brachial index.

Eighty-two patients were evaluated for erectile failure with a comprehensive history, physical examination, hormonal testing, noninvasive Doppler examination (PBI), and nocturnal penile tumescence (NPT). After these studies all patients received intracavernous injection with a combination of papaverine (50 mg) and phentolamine (1.66 mg), and both tumescence and rigidity were monitored. Rigidity response was compared with the PBI. The number of patients with a poor rigidity response in each PBI category were: 3 of 5 with a PBI of less than 0.6 (vasculogenic), 7 of 11 with a PBI of 0.6-0.75 (ambiguous), and 25 of 66 with a PBI of 0.75-1.0 (normal). These results indicate only a marginally significant association between PBI and intracavernous injection. The procedure was safe with no long-term sequelae from injection observed, and no surgical intervention was required. Complications of injections included reversible priapism in 11 patients (13.4%), transient dizziness in 10 patients (12.2%), and hematoma in 5 patients (6.2%). This study suggests that intracavernous injection with a drug combination may be a more sensitive screening test for vasculogenic impotence than noninvasive Doppler studies because it more closely simulates the erectile response.

Adult↗
PubMed1992

Factors predicting efficacy of phentolamine-papaverine intracorporeal injection for treatment of erectile dysfunction in diabetic male.

Thirty-three diabetic men were instructed in the use of phentolamine-papaverine injections for the treatment of erectile dysfunction over a two-year period. Of these, 12 reported a satisfactory response and 21 reported a nonsatisfactory response. The responders and the nonresponders were retrospectively studied to identify characteristics that would predict a satisfactory response. No difference was found between the two groups in the duration of diabetes, the presence of retinopathy, neuropathy, nephropathy, peripheral vascular disease, or ischemic heart disease. The utilization of insulin, the prevalence of type II diabetes, or the use of drugs which would cause impotence, did not differ between the two groups. There was no difference in the serum testosterone levels between the two groups. Age was the only predictive factor. Only 1 of 14 patients over age sixty had a satisfactory response to treatment while 11 of 19 patients under age sixty had a satisfactory response. Five of the responders and 2 of the nonresponders proceeded to penile implant surgery and reported satisfactory results. While older diabetic men may choose a trial of intracorporeal injections, they should be counselled regarding the high failure rate and alternative forms of therapy.

Age Factors↗
PubMed1980

Elimination of REM sleep rebound in rats by alpha-adrenoreceptor blockers, phentolamine and phenoxybenzamine.

Two alpha-adrenoreceptor blocking agents, phentolamine (5 mg/kg, IP) and phenoxybenzamine (10 mg/kg IP) were administered to rats deprived of rapid eye movement (REM) sleep for 24 hours to test the hypothesis that reduced noradrenergic transmission may abolish REM sleep rebound. The hypothesis was based on results from our previous studies which showed that administration to rats of diethyldithiocarbamate (DDC), a dopamine beta hydroxylase inhibitor, decreased the concentration of brain norepinephrine and reduced REM sleep permanently without the subsequent appearance of REM sleep rebound. Present results show that administration of both alpha-adrenoreceptor blockers abolished REM sleep rebound. At the time of maximum reduction of REM sleep, the concentration of 3-methoxy-4-hydroxyphenylethyleneglycol sulfate (MOPEGSO4), a final product of norepinephrine metabolism in the brain, was found increased in the whole brains of rats suggesting that the selected doses of the drugs were sufficient to produce effective central alpha-adrenergic receptor blockade. These data indicate that the action of both alpha-adrenoreceptor blocking agents in noradrenergic system was paralleled by the permanent loss of REM sleep and support the hypothesis implicating reduced noradrenergic transmission in elimination of REM sleep rebound.

Animals↗
PubMed1991

Phentolamine and thermoregulation in rats.

Phentolamine (PHEN), a nonselective alpha-adrenoceptor antagonist, causes a dose and ambient temperature (Ta)-dependent fall in body temperature (Tb) when injected intraperitoneally. In this paper, we investigated whether this was caused by integrated behavioral and autonomic thermoregulatory responses and whether it was due to a central action of the drug. Male rats were trained to press a bar for warm air in the cold or cold air in the heat. Rats were tested in both conditions near their Tb peaks and troughs after injections of saline or PHEN (5 and 10 mg/kg, IP). Tb fell significantly within the first 30 min post-PHEN, and after that, in the cold, the rats worked to increase Ta. In the heat they did not change Ta. To determine what was responsible for the Tb fall, we measured heat loss and heat production after saline or PHEN (10 mg/kg; IP) at Ta 2, 20, and 30 degrees C. Decreases in Tb at 2 and 20 degrees C were caused by increased heat loss during the first 15-30 min post-PHEN. At 2 degrees C, heat production increased after the drop in Tb. We conclude that the main reason the rats do not start to work immediately to prevent their core temperature from falling is that skin temperature is high, due to peripheral vasodilation, and that skin temperature is the major stimulus for regulating preferred Ta. We believe these effects are mediated by peripheral mechanisms because intracerebro-ventricular injections of PHEN did not cause a fall in Tb.

Animals↗
PubMed1981

Phentolamine increases neuronal binding and retrograde transport of dopamine beta-hydroxylase antibodies.

When 125I-labelled antibodies against dopamine beta-hydroxylase (DBH) were injected into the anterior eye chamber of guinea-pigs they bound to sympathetic nerve terminals, were internalized into the axons and retrogradely transported to the ipsilateral superior cervical ganglion (SCG). This process was demonstrated to depend on specific binding sites since neutralized antibodies were not taken up and transported. The alpha-receptor antagonist phentolamine caused a 2.5-fold increase in binding in the iris and a 2.1-fold increase in accumulation of [125I]anti-DBH in the SCG. The results demonstrate that retrograde axonal transport of synaptic vesicle components is coupled to their turnover in nerve terminals.

Afferent Pathways↗
PubMed1983

Hypoalgesia induced by the local injection of phentolamine in the nucleus raphe magnus: blockade by depletion of spinal cord monoamines.

Blockade of the noradrenergic input to the nucleus raphe magnus (NRM) by the injection of alpha-adrenergic antagonists produces hypoalgesia. Previous studies show that this hypoalgesia is blocked by the intrathecal injection of either phentolamine or methysergide. The present study demonstrates that depletion of spinal cord serotonin, norepinephrine, or both also blocks this hypoalgesia. Together these studies suggest that the hypoalgesia produced by microinjection of noradrenergic antagonists in the NRM is mediated by the activation of both raphe-spinal serotonergic neurons and bulbospinal noradrenergic neurons.

Animals↗
PubMed1994

Slowly developing placebo responses confound tests of intravenous phentolamine to determine mechanisms underlying idiopathic chronic low back pain.

Phentolamine (30 mg) was administered intravenously to subjects with idiopathic chronic low back pain in a novel placebo-controlled test to determine whether this alpha-adrenergic antagonist would reduce their pain. The effects of infusions on spontaneous pain and stimulus-evoked pains (touch, cold, tapping and deep pressure) were evaluated separately. All subjects gave strong placebo responses (reduced pain) that prevented assessment of specific drug effects. The placebo responses had onset latencies of 15-60 min, developed slowly over the next 15-45 min and persisted for hours or several days. These results not only reinforce the understanding that placebo controls are essential in the evaluation of drugs or other palliative procedures on patients with chronic pain but also indicate that the control paradigms must allow for placebo effects that are slow to develop and very persistent.

Adult↗
PubMed1991

The effects of intracerebroventricular injection of naloxone, phentolamine and methysergide on the transmission of nociceptive signals in rat dorsal horn neurons with convergent cutaneous-deep input.

In anaesthetized rats, recordings were made from nociceptive dorsal horn neurons with convergent input from the skin and deep somatic tissues. The results of a previous study have shown that in these neurons the input from deep nociceptors is subjected to a much stronger tonic descending inhibition than is the input from cutaneous nociceptors. The aim of the present study was to find out whether at supraspinal levels opioidergic, adrenergic, or serotoninergic transmitters are involved in this quite specific inhibition of deep nociception. Injections of naloxone, phentolamine, and methysergide into the third ventricle showed that only naloxone is capable of abolishing the tonic inhibition of the deep nociceptive input to spinal neurons. The input from cutaneous nociceptors to the same cells was largely unaffected by naloxone. Thus the effects of intracerebroventricular injection of naloxone resembled those obtained with a spinal cold block in a previous study; with the exception that the increase in background activity--which is prominent during cold block--was missing after the injection of naloxone. The present results demonstrate that the tonic descending inhibition of the deep nociception operates with opioidergic synapses at the supraspinal level. In contrast, supraspinal adrenergic and serotoninergic mechanisms do not appear to contribute to the tonic inhibition. The data confirm and extend previous results which suggested that a particular portion of the descending antinociceptive system may act mainly on the input from deep nociceptors. Pharmacologically, this particular portion seems to be opioidergic in nature.

Animals↗
PubMed1983

Effect of adrenergic blockade with bretylium and phentolamine on glomerular filtration rate in the rainbow trout, Salmo gairdneri Rich., adapting to saline water.

In resting conscious trout, Salmo gairdneri, a gradual increase in external salinity (brackish water) resulted in an immediate decline of glomerular filtration rate and urine flow. These renal responses were partly blocked by the administration of bretylium and phentolamine. The presence of adrenergic nerve endings in the trout kidney and these pharmacological results together provide evidence of neural control of renal haemodynamics. The action of vasoactive substances and innervation is discussed briefly in relation to their importance for normal renal function.

Adaptation, Physiological↗
PubMed1992

Phentolamine but not propranolol blocks the immunopotentiating effect of cold stress on antigen-specific IgM production in mice orally immunized with sheep red blood cells.

The effect of cold stress on immunocompetence was investigated in mice intragastrically intubated with sheep red blood cells. Cold stress was found to consistently augment total IgG and IgM production by splenic lymphocytes. In addition, antigen-specific IgM production by cultured splenic lymphocytes obtained from cold stressed animals was enhanced compared to unstressed mice. However, serum levels of total and antigen-specific immunoglobulins were suppressed or unaltered following cold stress. The alpha-adrenoceptor antagonist, phentolamine, could block the effects mediated by cold stress while the beta-adrenoceptor antagonist, propranolol, potentiated the action of cold stress. Taken together, the data indicate cold stress-mediated enhancement in immunoglobulin production by orally immunized animals takes place through the activation of alpha-adrenergic pathways. The results also suggest alpha- and beta-adrenergic pathways independently regulate antibody production following oral administration of antigen. These observations illustrate the integrative nature of the immune and neuroendocrine systems.

Animals↗
PubMed1984

Norepinephrine plus phentolamine improves regional blood flow during experimental low cardiac output syndrome.

A complication of cardiac surgical procedures is postoperative low cardiac output syndrome. Treatment with norepinephrine plus phentolamine (N + P) is beneficial, but the effect of these agents on regional organ blood flow has not been evaluated. Therefore, in 6 dogs with long-term instrumentation, pentobarbital was infused to simulate low cardiac output (32 + 10% of the conscious control level). Infusions of N + P at 0.2, 0.5, and 1.0 microgram/kg/min restored cardiac pump performance to conscious control levels. Regional blood flows, determined with tracer-labeled microspheres, were substantially reduced in the low cardiac output state but increased to values not markedly different from control levels in all organs studied except stomach fundus during infusion of N + P. The pressure-work index, an indirect measure of myocardial oxygen consumption, did not increase to more than the conscious level except at the highest dose. The data demonstrate that simultaneous infusion of N and P is capable of successfully improving cardiac pump performance with restoration of vital organ perfusion and without evidence of excessive myocardial oxygen consumption.

Animals↗
PubMed1978

The effect of phentolamine on intra-Hisian conduction.

A His bundle electrogram was obtained in a 70 year old male with syncopal episodes. A split bundle of His deflection was recorded. After the intravenous administration of phentolamine, a marked shortening of the H-H' interval was observed. This signifies an improvement in conduction at the bundle of His level.

Action Potentials↗
PubMed1977

The phentolamine test in neurogenic bladder dysfunction.

In an attempt to improve the selection of patients with neurogenic bladder dysfunction likely to benefit from phenoxybenzamine therapy, the effect of intravenous phentolamine (Regitine) on the urinary flow rate was determined in normal and abnormal subjects. A nomogram relating mean flow rate to volume voided was constructed to aid in the interpretation of results. In 16 patients with neurogenic bladder dysfunction it was found that a response of more than 0.8 nomogram units indicates a likelihood of clinical improvement with phenoxybenzamine therapy. The clinical applications of this test are discussed.

Adult↗