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At least 199 records · Page 11Linked to original sources
PubMed1987

Release of endogenous monoamines into spinal cord superfusates following the microinjection of phentolamine into the nucleus raphe magnus.

Previous studies have suggested that raphe-spinal neurons located in the nucleus raphe magnus (NRM) are tonically inhibited by noradrenergic neurons. Furthermore, blockade of the inhibitory noradrenergic input to the NRM induces antinociception which appears to be mediated by the release of both serotonin and norepinephrine in the spinal cord. The present experiments were designed to directly measure the release of endogenous serotonin and norepinephrine into spinal cord superfusates before and after the microinjection of the alpha-adrenergic antagonist phentolamine into the NRM. High-performance liquid chromatography with electrochemical detection was used to quantitate the monoamines. The injection of phentolamine into the NRM induced a significant increase in the amount of both norepinephrine and serotonin released in the spinal cord. This enhanced release was not observed following either the injection of phentolamine into sites outside the NRM or the injection of saline vehicle into the NRM. These results support the proposal that the antinociception induced by the blockade of the inhibitory noradrenergic input to the NRM is mediated by the activation of spinally-projecting serotonergic and noradrenergic neurons.

Animals↗
PubMed1989

Effects of intracerebroventricular infusions of naltrexone and phentolamine on central and peripheral oxytocin release and on maternal behaviour induced by vaginocervical stimulation in the ewe.

The effects of intracerebroventricular infusions of naltrexone and phentolamine on the ability of vaginocervical stimulation to induce maternal behaviour, and plasma and cerebrospinal fluid (CSF) levels of oxytocin, were measured in oestrogen-primed ewes. Results showed that naltrexone, but not phentolamine, significantly inhibited maternal behaviour following vaginocervical stimulation. Naltrexone also prevented the CSF increase in oxytocin following vaginocervical stimulation but was without effect on plasma levels. Phentolamine did not prevent either CSF or plasma increases in oxytocin, following vaginocervical stimulation, but reduced basal plasma levels. Results are discussed in terms of an opioid influence on maternal behaviour which may be mediated through a modulation of central oxytocin release.

Animals↗
PubMed1978

Some observations on the gastric effects of phentolamine in rats.

The effects of graded doses of phentolamine on gastric secretion, gastric emptying rate, gastric mucosal mucus content and gastric mucosal lesion incidence were studied in conscious rats 2 h after intramuscular administration. In pylorus-occluded rats, phentolamine (5, 10 or 20 mg/kg) produced dose-dependent decreases in the gastric secretory volume and total acid output. Similar doses of the drug also produced dose-dependent decreases in the gastric emptying rate in animals without pylorus occlusion (intact rats), but did not affect the gastric mucosal mucus content. The incidence of gastric mucosal lesions in pylorus-occluded or intact animals rose with increasing doses. The findings are discussed in the light of the possibility that phentolamine, in the dose range examined, possesses a sympathomimetic action which would underlie the gastric lesions observed.

Animals↗
PubMed1984

Myometrial responses in situ to nicergoline, acebutolol, phentolamine and noradrenaline of the rat in proestrus.

The effects of two adrenoceptor antagonists, nicergoline (alpha 1) and acebutolol (beta 1), on the contraction of myometrium in the proestrous rat were compared to those of noradrenaline and phentolamine. The spontaneous myometrial contractions of Wistar rats on the day of proestrus were recorded isometrically and the data were analysed using Wilcoxon non-parametric statistics. All drugs were administered i.v. and the doses are expressed as microgram/kg body weight. Noradrenaline (1200 micrograms/kg per h) induced a 32.5% reduction (P less than 0.001) of the uterine contraction amplitude. Nicergoline did not alter uterine motility significantly when administered alone at doses ranging from 400 to 1600 micrograms/kg. However, successive injections of nicergoline in the same range given during noradrenaline infusion at 600 micrograms/kg per h potentiated the relaxing action of the latter (38%, P less than 0.01). Phentolamine (120 micrograms/kg) reduced myometrial activity by 25% (P less than 0.05). This inhibitory response rose to 65% (P less than 0.001) when the dose of phentolamine was increased to 960 micrograms/kg. When a single injection of nicergoline (400 micrograms/kg) was followed by the administration of increasing doses of acebutolol (120, 1200, 2400 micrograms/kg) the slight inhibitory effect on uterine motility observed after administration of each of the two agents separately became more pronounced (P less than 0.05). It appears from these results that combining noradrenaline with nicergoline and nicergoline with acebutolol leads to potentiation of their relaxing effects. Furthermore the results confirm that nicergoline is a partial alpha-blocker.

Acebutolol↗
PubMed1978

Effect of phentolamine on the somatostatin-induced inhibition of glucagon and insulin secretion.

Synthetic cyclic somatostatin was infused into either the cranial pancreaticoduodenal artery or the femoral vein of anesthetized dogs with or without previous administration of phentolamine. Somatostatin infused into the pancreatic artery at a dose of 50 ng/kg/min for 10 min caused significant decreases in blood flow and plasma basal concentrations of both glucagon and insulin in the cranial pancreaticoduodenal vein, resulting in a profound decline of bihormonal output during the infusion. Arterial plasma glucose was not reduced during the administration of somatostatin in the pancreatic artery. These somatostatin-induced decreases failed to be eliminated by a 0.2 mg/kg injection of phentolamine into the femoral vein followed by a 9-min infusion of this alpha-adrenergic blocker (0.02 mg/kg/min) into the pancreatic artery immediately prior to the somatostatin administration. An inhibition of glucagon and insulin output and a fall of plasma glucose caused by somatostatin (1.7 microgram/min) infused into the femoral vein for 30 min also were not abolished by a prolonged and simultaneous infusion of phentolamine (0.2 mg/min) into the femoral vein over a period of 2 hr. These results indicate that alpha-adrenergic receptor mechanisms do not play a major role in the inhibition of islet glucagon and insulin secretion by somatostatin.

Animals↗
PubMedDate not supplied

Enhancement of the hypothermic response of mice to delta-9-tetrahydrocannabinol by subhypothermic doses of chlorpromazine and phentolamine.

Pretreatment with subhypothermic doses of chlorpromazine, given directly into the IIIrd cerebral ventricle via a chronically implanted cannula (50 micrograms) or subcutaneously (0.75 mg/kg), was found to enhance the hypothermic response to delta-9-tetrahydrocannabinol (THC: 5 20 mg/kg i.p.) in unrestrained adult male MF1 mice, kept at 22 degrees C. Subcutaneous pretreatment with a subhypothermic dose of phentolamine (30 mg/kg) had a similar effect, whereas pretreatment with desipramine (10 mg/kg s.c.), mepyramine (2.3 and 11.5 mg/kg s.c.), methysergide (2 mg/kg s.c.), pimozide (1 and 5 mg/kg s.c.) or lignocaine (50 mg/kg s.c.), had no effect. Intracerebroventricular pretreatment with phentolamine was also without effect and it is concluded that this drug interacts with THC at some site located outside the brain. Since, in mg/kg terms, chlorpromazine was more potent in enhancing THC-induced hypothermia when given subcutaneously than when injected into the IIIrd ventricle, it too may interact with THC at a peripheral site. Indeed, chlorpromazine and phentolamine may both increase the hypothermic response to THC by antagonizing alpha-adrenoceptors on cutaneous blood vessels, thereby decreasing the capacity of animals to minimise peripheral blood flow by vasoconstriction. Alternatively, since the distribution of chlorpromazine within the brain may well have been less efficient after intraventricular than after subcutaneous injection, the possibility remains that chlorpromazine interacted centrally with THC.

Animals↗
PubMed1984

Injections of phentolamine into the anterior hypothalamus-preoptic area of rats blocks both pressor and drinking responses produced by central administration of angiotensin II.

There are conflicting reports of a possible contribution of noradrenergic projections to the rostral hypothalamus to drinking and blood pressure regulation. The present study investigated the effects of injecting phentolamine into the anterior hypothalamus-preoptic region on drinking and blood pressure responses elicited by injecting angiotensin II into a lateral cerebral ventricle of the rat. Angiotensin II (250 ng or 25 ng) elicited water intakes averaging 9.25 +/- 0.52 ml and 4.35 +/- 0.44 ml respectively in 15 min with latencies of less than 3 min. Phentolamine, an alpha-adrenergic antagonist, injected into the rostral hypothalamus produced a dose-dependent reduction in water intake and number of laps taken accompanied by an increased latency to drink. In the urethane anaesthetized rat, angiotensin II produced significant increases in blood pressure. Injections of phentolamine into rostral hypothalamic sites in which drinking responses to angiotensin II were attenuated, also attenuated the pressor response to angiotensin II. These results indicate that alpha-adrenergic input to the rostral hypothalamus is involved in both the pressor and drinking responses elicited by central angiotensin II.

Angiotensin II↗
PubMed1982

Comparison of the non-adrenergic action of phentolamine with that of vanadate on cochlear function.

Two drugs, which upon superficial examination appeared to be acting on common processes, have been found upon closer investigation to act by quite different means. Both act primarily at the organ of Corti, causing a pronounced increase of the endocochlear potential and a depression of the cochlear microphonic (CM). These effects are accompanied by the elimination of a negative component of the EP; however, it was found that these three effects are produced by phentolamine in scala media (or, more slowly, in scala tympani) but by vanadate only in scala tympani. This difference in locus of action isd manifested further by different changes of the summating potential (SP): phentolamine has little effect on the magnitude of SP-, while vanadate leads to an elevated SP-. In spite of this difference in the 'zeroth order harmonic', the second harmonic of the CM is depressed by both agents. It is argued that phentolamine may act either by blocking the acoustically-modulated ion channels in the luminal membranes of the hair cells or by inducing a large, non-selective, paracellular conductance in the organ of Corti. The present results, in conjunction with our previous results (Marcus, D.C., DeMott, J.E., Kobayashi, T., Ge, X.-X. and Thalmann, R. (1981): Hearing Res. 5, 231-243), are further interpreted as suggesting that vanadate may initially act by depolarizing the hair cells.

Adrenergic alpha-Antagonists↗
PubMed2005

Individual differences in the sensitivity of cold allodynia to phentolamine in neuropathic rats.

In neuropathic rats sensitive to phentolamine (alpha-adrenoreceptor antagonist, 2 mg/kg, i.p.), prazosin (alpha1-adrenoreceptor antagonist, 0.5 mg/kg, i.p.) significantly attenuated cold allodynia whereas yohimbine (alpha2-adrenoreceptor antagonist, 0.5 mg/kg, i.p.) had no significant effect. In neuropathic rats insensitive to phentolamine, yohimbine significantly exacerbated cold allodynia whereas prazosin had no significant effect. These results suggest that the individual differences in the sensitivity of cold allodynia to phentolamine may be due to the difference in the alpha-adrenoreceptor subtype predominantly involved in cold allodynia.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1983

The hemodynamic effect of phentolamine and dobutamine after open-heart operations in children: influence of the underlying heart defect.

The hemodynamic effects of phentolamine alone and in combination with dobutamine were studied in the immediate postoperative period in two groups of children. Group 1 (N = 6; mean age, 152 months) had open-heart operation for acquired mitral valve disease. Group 2 (N = 6; mean age, 60 months) had intracardiac repair for tetralogy of Fallot. Before drug administration, cardiac index did not differ between groups, but patients with tetralogy of Fallot had a higher heart rate and smaller stroke volume index; systemic vascular resistance was high in both groups. With phentolamine (10 micrograms/kg/min), cardiac index and stroke volume index increased similarly in both groups (+ 13% for cardiac index in Group 1, +9% in Group 2), while systemic vascular resistance, pulmonary vascular resistance, and pulmonary wedge pressure decreased. When dobutamine (5 micrograms/kg/min) was added, there was a further increase in cardiac index in both groups, but it was greater in Group 1 (+17% vs +12%, p less than 0.01, compared with phentolamine alone; +33% vs +22%, p less than 0.01, compared with control). Systemic vascular resistance remained unchanged and heart rate increased in both groups, so that the left ventricular stroke work index increased. Although stroke volume index increased significantly with dobutamine in Group 1 (+11%, p less than 0.01), it remained unchanged in Group 2 (+3%, not significant). Thus in Group 2, dobutamine increased cardiac index only by increasing heart rate. This suggests that the relatively small, noncompliant left ventricle in patients with tetralogy of Fallot cannot further respond to inotropic drugs by increasing stroke volume index.

Adolescent↗
PubMed1991

Intracavernous injection of prostaglandin E1 in combination with papaverine: enhanced effectiveness in comparison with papaverine plus phentolamine and prostaglandin E1 alone.

We compared the erectile response to intracavernous injection of a combination of papaverine and prostaglandin E1 with that of a combination of papaverine and phentolamine (49 patients), and prostaglandin E1 alone (38). The degree of erection achieved was significantly better with papaverine plus prostaglandin E1 than with papaverine plus phentolamine and the duration of erection was less, although the incidence of prolonged erections (greater than 5 hours) was similar with both combinations. Papaverine with prostaglandin E1 likewise resulted in a significantly better degree of erection than prostaglandin E1 alone (prolonged erections occurred only after the drug combination). All erections subsided spontaneously and none required medical intervention throughout the study. Pain was noted only after injection of prostaglandin E1. The incidence was clearly lower (7 of 38 versus 13 of 38) after the injection of only 5 micrograms. prostaglandin E1 in combination with papaverine (although the difference is not statistically significant). Subjectively, the side effects caused by the drug combination were described as much less dramatic by the patients than after prostaglandin E1 alone. The combination of papaverine and prostaglandin E1 shows a clearly synergistic effect and might suitably replace papaverine plus phentolamine or prostaglandin E1 alone in patients who do not respond well or suffer side effects after high single doses.

Adult↗
PubMed1989

The pH analysis of papaverine-phentolamine and prostaglandin E1 for pharmacologic erection.

Although papaverine-phentolamine preparations are being employed for pharmacologic erection programs across the nation, their chemical properties have not been described in the literature. We found that the pH of papaverine-phentolamine solution in all concentrations tested remained less than 4.0. Attempts to buffer the solution resulted in a precipitate at a pH greater than or equal to 5.0. The pH of prostaglandin E1 was less than 5.0 but could be easily buffered to pH 7.4 or even 10.75 and remained stable. The effect of an acidic solution on corporal connective tissue and smooth muscle meshwork is unknown. We believe that buffering by blood will lead to the precipitation of papaverine-phentolamine and may cause primary intracorporal scarring. Extravasation or improper injection into the subcutaneous tissue exposes the mixture to blood and may secondarily result in additional scarring for the same reason. Therefore, prostaglandin E1 may be a more appropriate agent for penile injection.

Alprostadil↗
PubMed1981

Gas chromatographic determination of phentolamine (Regitine) in human plasma and urine.

A method for the determination of unconjugated phentolamine at concentrations down to 5 ng/ml in human plasma, and of free and total (free plus conjugated) phentolamine down to 25 ng/ml in urine is described. After addition of 2-[N-(p-chlorophenyl)-N-(m-hydroxyphenyl)-aminomethyl]-2-imidazoline as internal standard, both compounds are extracted into benzene-ethyl acetate (1:1, v/v) at pH 10, transferred into an acidic aqueous solution and back-extracted at pH 10 into benzene-ethyl acetate. They are then derivatized with N-heptafluorobutyrylimidazole. The derivatives are determined by gas chromatography using a 63Ni electron-capture detector. In urine, total (free plus conjugated) phentolamine is determined after enzymatic hydrolysis. The technique was applied for the study of the plasma concentrations and urinary elimination after oral administration to man.

Arylsulfatases↗
PubMed1989

Vasodilator properties of atrial natriuretic factor: a comparison with nitroglycerin, nitroprusside, and phentolamine during cardiopulmonary bypass.

Thirty-five patients scheduled for coronary artery surgery were studied during hypothermic cardiopulmonary bypass (CPB) to compare the arteriolar and venodilator properties of a bolus dose of atrial natriuretic factor (ANF), 100 micrograms, with those of nitroglycerin, 200 micrograms, sodium nitroprusside, 120 micrograms, phentolamine, 3 mg, and placebo. A decrease observed in mean arterial pressure was used as an indicator of a decrease in systemic vascular resistance (arteriolar dilation), while a decrease in reservoir blood volume of the CPB circuit was considered to indicate an increase in venous capacitance (venodilation). All vasodilators decreased mean arterial pressure, and there was no difference in the maximal decrease of the pressure between the drugs. However, the decrease caused by ANF appeared later than that caused by the other vasodilators and lasted longer than with nitroglycerin and sodium nitroprusside. Nitroglycerin and sodium nitroprusside decreased reservoir blood volume, while ANF and phentolamine had no effect. It is concluded that ANF is an arteriolar dilator with a time profile of its effect differing from those of nitroglycerin, sodium nitroprusside, and phentolamine. ANF seems to have no venodilator activity in patients undergoing hypothermic CPB.

Atrial Natriuretic Factor↗
PubMed2001

Effects of haloperidol and phentolamine on the crustacean cardiac ganglion.

Haloperidol (a dopamine D2 blocker in vertebrates) and phentolamine (an alpha-adrenergic blocker) alter the pattern of bursting by the isolated cardiac ganglion of the lobster when perfused at concentrations of 10(-6)-10(-5) mol/l. Both drugs decrease the frequency of bursting and increase burst duration. They are most effective in slowing the ganglion when applied selectively to the anterior ganglionic trunk, the same region of the ganglion where dopamine (DA) and 5-hydroxytryptamine (5HT) are most effective in speeding up bursting. When exogenous monoamine transmitters are applied in the presence of 3x10(-6) mol/l haloperidol, the effect of 5HT, but not of DA, is significantly reduced. At the same concentration, phentolamine does not suppress the actions of DA, 5HT or noradrenaline (NA). Both haloperidol and phentolamine significantly alter the properties of endogenous burst-organizing potentials (driver potentials) generated by motorneurons in the ganglion. It is possible that the effects of these drugs on bursting reflect alteration of endogenous electrical properties of the constituent neurons, rather than receptor antagonism.

Adrenergic alpha-Antagonists↗
PubMed2001

Phentolamine suppresses the increase in arteriolar vasomotion frequency due to systemic hypoxia in hamster skeletal muscle microcirculation.

Systemic hypoxia (8%, 11% and 15% oxygen gas mixture inspiration) has been shown to increase the frequency of arteriolar rhythmic diameter changes in hamster skeletal muscle microcirculation. The effects of phentolamine on vasomotion frequency during systemic hypoxia were studied in Syrian hamsters implanted with a plastic chamber in the dorsum skin. Phentolamine (50 microg/100 g body wt.) was injected intravenously before the 20-min exposure to 11% oxygen gas mixture. The microvessels were studied with a fluorescent microscopy technique, using fluorescein isothiocyanate bound to dextran (mol. wt. 150,000) as a tracer. Vessel diameters were measured with a shearing method. Fourier transform and autoregressive modeling were used to assess the time variant features of diameter changes. Under baseline conditions, the arterioles were characterized by rhythmic diameter changes with fundamental frequency related to vessel size. The terminal branchings were dominated by order 3 vessel activity (frequency: 0.08-0.16 Hz) spreading downstream to all daughter arterioles. Systemic hypoxia caused an increase in vasomotion frequency of order 3 arterioles up to 0.3-0.5 Hz (average: 0.40 +/- 0.06 Hz) and a significant decrease in mean diameter (-28 +/- 5%). Phentolamine completely suppressed the rhythmic changes in diameter of order 3 arterioles that dilated significantly (+ 30 +/- 4%). Therefore, the effects of systemic hypoxia on arteriolar vasomotion appear to be triggered by an increase in sympathetic nervous discharge that induces a rise in frequency up to 0.3-0.5 Hz.

Animals↗
PubMedDate not supplied

Development of hibernomas in rats dosed with phentolamine mesylate during the 24-month carcinogenicity study.

Phentolamine is a reversible competitive alpha-adrenergic antagonist with similar affinities for alphal and alpha2 receptors. It has a long history of safe clinical use, and was developed as a potential therapy for male erectile dysfunction because of its capacity to increase the arteriolar blood flow to the corpora cavernosa. Phentolamine mesylate was administered to rats by oral gavage at daily doses of 10, 50, and 150 mg/kg for 24 months. A dose-related increase in mortality, ascribed to an exaggerated pharmacologic effect, was seen at high doses. Systemic exposure as measured by plasma drug concentration increased with dose and duration of dosing and slight drug accumulation occurred, particularly in high-dose males. In the treated groups, 10 males and 1 female were diagnosed with hibernomas, neoplasms of brown adipose tissue, which appeared in the thoracic cavity or retroperitoneal area as circumscribed, tan to reddish-brown lobulated masses. Histologically, the masses were well circumscribed with variably sized lobules defined by a rich capillary network and consisted of closely apposed oval to polygonal cells with large amounts of cytoplasm and a centrally located nucleus. The cytoplasm's appearance varied from multivacuolated to univacuolated to granular eosinophilic. In a few cases, neoplastic emboli were observed in capsular vessels. Ultrastructurally, the neoplastic cells contained numerous mitochondria with transverse parallel cristae that occupied over 60% of the cytoplasm and lipid droplets. This study documents the previously unreported development of hibernomas in rats treated with phentolamine mesylate.

Administration, Oral↗
PubMed1982

Effect of phentolamine on the metabolic response to gynaecological surgery.

The effect of the infusion of phentolamine 0.5 mg min-1 on the metabolic response to gynaecological surgery was investigated. In comparison with the control group of patients, phentolamine was associated with a significant increase in plasma insulin concentration after 30 and 60 min of surgery. The glycaemic response to surgery was decreased by alpha-adrenergic blockade, but this was only significant after 120 min of surgery. The hypotension produced by the administration of phentolamine was well tolerated.

Adult↗