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At least 19 recordsLinked to original sources
PubMed2005

Assessment of the efficacy of phentolamine to prevent radial artery spasm during cardiac catheterization procedures: a randomized study comparing phentolamine vs. verapamil.

The objective of this study was to evaluate phentolamine as radial artery spasmolytic in transradial catheterization procedures. Radial artery spasm is a relatively frequent complication during transradial approach, causing patient discomfort or even making it impossible to continue the procedure. As radial artery spasm is mediated by the stimulation of alpha-adrenoreceptors, the use of the alpha-blocker phentolamine could make sense as spasmolytic. We designed a randomized double-blind study to compare phentolamine vs. verapamil, the standard spasmolytic agent. Five hundred patients (250 in each arm) submitted to a transradial cardiac catheterization were consecutively included and randomly assigned to receive 2.5 mg of verapamil or 2.5 mg of phentolamine after sheath insertion. Both vasodilator agents induced a significant radial artery diameter increase (from 2.22 +/- 0.53 to 2.48 +/- 0.57 mm, P < 0.001 for verapamil, and from 2.20 +/- 0.53 to 2.45 +/- 0.53 mm, P < 0.001 for phentolamine). However, verapamil was more efficacious to prevent radial artery spasm (13.2% compared with 23.2% in phentolamine-treated patients; P = 0.004). Follow-up (20 +/- 18 days) evaluation of the radial artery patency by plestismography and pulse oximetry showed no differences between the two groups in the rate of radial occlusion (3.0% vs. 3.2% in verapamil and phentolamine treated patients, respectively). Phentolamine was an effective radial vasodilator agent, although it showed less ability to prevent radial artery spasm than verapamil. Radial artery occlusion rate was almost identical for both vasodilators. Thus, phentolamine could be a valid alternative to verapamil as a radial artery spasmolytic agent.

Adrenergic alpha-Antagonists↗
PubMed1995

Papaverine-phentolamine and prostaglandin E1 versus papaverine-phentolamine alone for intracorporeal injection therapy: a clinical double-blind study.

PURPOSE: A study was designed to compare intracorporeal injections of papaverine plus phentolamine (2-drug solution) and papaverine plus phentolamine and prostaglandin E1 (3-drug solution) for the treatment for impotence. MATERIALS AND METHODS: A total of 20 impotent patients received intracorporeal injections of the 2-drug or 3-drug solution alternately during 2 sessions, and the quality and duration of erections were assessed. RESULTS: Of the patients 73% achieved a full erection with the 3-drug solution compared to 28% with the 2-drug solution. The average duration of erections was 57 minutes and 33.6 minutes, respectively. The complication rate was similar for the 2 treatments. CONCLUSIONS: Papaverine plus phentolamine and prostaglandin E1 is superior to papaverine plus phentolamine alone for the treatment of impotence.

Adult↗
PubMed1996

Prostaglandin E1 versus mixture of prostaglandin E1, papaverine and phentolamine in nonresponders to high papaverine plus phentolamine doses.

PURPOSE: We evaluated the efficacy of 40 micrograms/ml, prostaglandin E1 versus a combination of 17.64 mg./ml. papaverine hydrochloride, 0.58 mg./ml. phentolamine mesylate and 5.8 micrograms/ml. prostaglandin E1 (3-drug mixture). MATERIALS AND METHODS: A total of 32 patients randomly received 1 ml. of either medication by the intracavernous route. All patients had presented with erectile dysfunction longer than 6 months in duration and had failed to respond to high doses of papaverine (60 mg.) plus phentolamine (1 mg). RESULTS: Of 32 patients 7 (22%) responded to prostaglandin E1 and 16 (50%) to the 3-drug mixture, achieving erections allowing penetration (grade E4 or E5, p < 0.05). Pain was reported by 41% of the patients receiving prostaglandin E1 and 12.5% administered the 3-drug mixture. CONCLUSIONS: The 3-drug mixture may be regarded as more effective than prostaglandin E1 alone in inducing an erectile response with a decreased incidence of pain.

Adult↗
PubMed1995

Local and systemic phentolamine antagonism of norepinephrine-induced hand vein constriction.

The dorsal hand vein distention technique has been used to study the effects of alpha-adrenergic receptor antagonists on alpha-agonist-induced venoconstriction. Using this technique, we investigated the dose-effect relationships between different intravenous routes of phentolamine (an alpha-antagonist) administration on norepinephrine (an alpha-agonist)-induced hand vein constriction. Hand vein studies were done on healthy men; each man was studied on up to four occasions. On one occasion for each man, graded doses of phentolamine were infused into a hand vein preconstricted (submaximally) with norepinephrine. The dose of phentolamine producing a half maximal response (ED50) for reversal of venoconstriction, and the maximal reversal were calculated. On the other three occasions (randomly allocated) for each man, graded doses of norepinephrine were infused into a hand vein before and during intravenous infusions of (1) control (vehicle solutions); (2) systemic (other arm vein) phentolamine; and (3) local (hand vein) phentolamine. Systemic and local phentolamine dose ratios (ED50 of norepinephrine during phentolamine, divided by ED50 of norepinephrine before phentolamine; divided by the control dose ratio) were calculated. These studies show that phentolamine (administered directly into a preconstricted hand vein) can completely reverse norepinephrine-induced venoconstriction. Phentolamine, administered by either local or systemic intravenous infusion, induces a significant rightward shift (approximately 10-fold) in responsiveness to norepinephrine-induced venoconstriction. To achieve comparable degrees of alpha-antagonism, however, systemic phentolamine must be administered intravenously at a dose approximately 3,000-fold higher than that of local phentolamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1996

Monitoring adequacy of alpha-adrenoceptor blockade following systemic phentolamine administration.

Systemic phentolamine administration has been suggested as a diagnostic tool for identifying patients with sympathetically maintained pain (SMP) (Raja et al. 1991). The dose of phentolamine to produce adequate blockade of peripheral alpha-adrenoceptor function has, however, not been previously determined. In this study, the effects of two different doses of phentolamine on peripheral sympathetic vasoconstrictor function were investigated. One-hundred and seventeen (117) patients with chronic extremity pain underwent 130 phentolamine diagnostic tests using two different doses of phentolamine (0.5 mg/kg over 20 min (n = 60) and 1 mg/kg over 10 min (n = 59)). Eleven (11) patients did not receive phentolamine during the test. Cutaneous temperature was measured in the distal extremity before and after administration of phentolamine. In a subset of patients, baseline blood flow and sympathetically mediated vasoconstrictor response (SMR) to deep inhalation were measured on glabrous skin using laser Doppler flowmetry. SMR was elicited with a 5-sec maximal inspiratory gasp. A dose-related increase in cutaneous temperature was observed. In addition, baseline blood flow increased and SMR was attenuated after both doses of phentolamine, but to a greater degree after the 1 mg/kg dose. However, SMR was not completely attenuated, even after administration of the higher phentolamine dose. These results indicate that a phentolamine dose of 1 mg/kg over 10 min more completely blocks alpha-adrenoceptor function than a dose of 0.5 mg/kg over 20 min. We therefore recommend that to ensure adequate alpha-adrenoceptor blockade the higher phentolamine dose be used in the phentolamine diagnostic test for SMP.

Adolescent↗
PubMed1988

An assay for phentolamine using high performance liquid chromatography with electrochemical detection.

A new method is presented for the detection of phentolamine by high performance liquid chromatography with electrochemical detection. The electrochemical detector was used in the oxidative mode at +900 mV potential versus Ag/AgCl reference. The on-column detection limit for phentolamine using this method was 3 ng, and detector response was linear for 3-1000 ng injected on column. The coefficient of variation for replicate injections was 2.4%. The measurement of phentolamine in biological samples was accomplished using yohimbime as the internal standard; retention time for yohimbine was 3.0 min while phentolamine eluted at 4.75 min. Biological samples were buffered to pH 9.2 and extracted with diethyl ether, followed by back extraction into 0.1 N HCl. The extraction efficiency for this method was 99.4% for phentolamine in serum and 59.3% in liver tissue. The detection limit for phentolamine was 5 ng/ml for 1.0-ml serum samples, and was 10 ng/ml for 1.0-ml liver homogenate samples. The disappearance of phentolamine from serum and liver after administration of a single ip dose of phentolamine to mice was determined using this method. Absorption from the ip route was rapid, with peak phentolamine concentrations achieved in 15 min or less. The elimination half-life of phentolamine in serum was approximately 50 min and was paralleled by disappearance of phentolamine in the liver.

Animals↗
PubMed1983

Differential inhibition of 5-hydroxytryptamine (5-HT) mediated contraction of rat thoracic aortae by phentolamine and tolazoline: correlation with inhibition of 5-HT binding and calcium ion.

The contribution of alpha receptor stimulation to the contractile responses of vascular smooth muscle to 5-HT was evaluated, in vitro utilizing helical strips of rat thoracic aortae (RTA). The contractile responses of RTA to 5-HT and norepinephrine (NE) were inhibited by the alpha receptor blocking agent phentolamine. The inhibition persisted in RTA obtained from rats treated with reserpine (1.5 mg/kg/day for 6 days). Analysis of the interaction of phentolamine with 5-HT and NE demonstrated that: 1) phentolamine is a competitive inhibitor of the responses to 5-HT; and 2) the pA2 values for the interaction of phentolamine with 5-HT and NE differed. When the concentration of calcium ion in the physiologic saline solution (PSS) was increased from 1.6 mM to 2.5 mM, phentolamine was approximately 100 times more potent an inhibitor of the response to NE than 5-HT. Phentolamine decreased the binding of 14C-5-HT to rat thoracic aortae in control PSS, but not when the calcium concentration was increased to 2.5 mM. Tolazoline inhibited the contractile responses of RTA to NE but not 5-HT. The data support the conclusion that the contractile responses of RTA to 5-HT are mediated by receptors similar to the alpha receptor. The ability of phentolamine to inhibit 5-HT induced contraction may be dependent on the ability of phentolamine to bind to anionic sites of the 5-HT receptor. The inhibitory effect of calcium ion may result from its ability to combine with, and neutralize, these negatively charged moieties on the smooth muscle membrane. The lack of effect of tolazoline may result from the absence of the third ring structure present in the phentolamine molecule, and therefore an inability to bind to these postulated anionic sites. Alternatively, the absence of an imino-nitrogen in the chain separating the phenyl and imidazole groups of tolazoline may prevent tolazoline from interacting with the 5-HT receptor. The different pA2 values for phentolamine mediated inhibition of the responses to 5-HT and NE, and the ability of NE to poorly displace 5-HT from the RTA, despite blockade of alpha receptors with tolazoline, support the possibility that the 5-HT receptor of RTA differs from the alpha receptor and that phentolamine has affinity for both 5-HT and adrenergic receptors.

Animals↗
PubMed1976

Phentolamine.

The clinical uses of phentolamine have widened since its introduction as an anti-hypertensive agent. The vasodilating action of the drug as well as its postive inotropic effects have led to its use in treating congestive heart failure. Recently, phentolamine has been use by several groups to improve left ventricular function in acute myocardial infarction. There appears to be great promise for the use of phentolamine in this clinical setting. The drug given intravenously or orally can suppress ventricular premature beats and supraventricular premature beats. However, the experience of phentolamine as an antiarrhythmic agent is still limited. Similarly, the relief of angina pectoris by phentolamine requires confirmation by additional clinical studies. Phentolamine can be used as a provocative test in idiopathic hypertrophic subaortic stenosis. Since it does not produce cardiac arrhythmias, it may be safer than isoproterenol. The comparative effectiveness of phentolamine and isoproterenol in diagnosing I.H.S.S. is unknown. Phentolamine has been advocated for several years as a beneficial agent for the treatment of shock. The experience is still limited to a few groups who have reported favorable results. Phentolamine has been used as a bronchodilator and a pulmonary artery dilator. The preliminary reports appear favorable. However, continused investigation is warranted. A sensitive measurement of the blood levels of phentolamine is not available. When this is accomplished, further insight into the metabolism of this drug will be forthcoming.

Angina Pectoris↗
PubMed1990

Phentolamine and yohimbine inhibit ATP-sensitive K+ channels in mouse pancreatic beta-cells.

1. The effects of phentolamine and yohimbine on adenosine 5'-triphosphate (ATP)-sensitive K+ channels were studied in normal mouse beta-cells. 2. In the presence of 3 mM glucose, many ATP-sensitive K+ channels are open in the beta-cell membrane. Under these conditions, phentolamine inhibited 86Rb efflux from the islets. This inhibition was faster with 100 than with 20 microM phentolamine but its steady-state magnitude was similar with both concentrations. Yohimbine (20-100 microM) also inhibited the efflux rate but was not as potent as phentolamine. 3. In the presence of 6 mM glucose, most ATP-sensitive K+ channels are closed in the beta-cell membrane. Their opening by 100 microM diazoxide caused a marked acceleration of 86Rb efflux from the islets. This acceleration was almost entirely prevented by 20 microM phentolamine. It was barely affected by 20 microM yohimbine and reduced by 50% by 100 microM yohimbine. 4. ATP-sensitive K+ currents were studied in single beta-cells by the whole cell patch-clamp technique. Phentolamine (20-100 microM) caused a progressive but almost complete and irreversible inhibition of the current. The effects of yohimbine were faster but smaller; the inhibition was still incomplete with 100 microM yohimbine. 5. The increase in ATP-sensitive K+ current produced by 100 microM diazoxide was prevented by 100 microM phentolamine but only partially attenuated by 100 microM yohimbine. 6. It is concluded that phentolamine inhibits ATP-sensitive K+ channels in pancreatic beta-cells. This novel effect of phentolamine resembles that of hypoglycaemic sulphonylureas. It may account for previously unexplained effects of the drug. These observations also call for reinterpretation of many studies in which phentolamine was used as an allegedly specific blocker of alpha-adrenoceptors.

Adenosine Triphosphate↗
PubMed1995

Alpha 1- and alpha 2-adrenoreceptor actions of phentolamine and prazosin on breathing movements in fetal sheep in utero.

1. We studied the effects of systemic administration of the alpha 1- and alpha 2-adrenoreceptor antagonist phentolamine and the selective alpha 1-adrenoreceptor antagonist prazosin on fetal breathing movements (FBM) and electrocortical activity (ECoG) in fetal sheep. In one group of fetuses (group I; n = 7) the effects of phentolamine were measured during normoxia and hypoxia. In the second group of fetuses (group II; n = 8) the effects of either phentolamine, or combined phentolamine and prazosin, or prazosin alone, were measured during normoxia. 2. In group I fetuses, the incidence of FBM increased after phentolamine treatment. An increase in the incidence and mean episode duration of low-voltage ECoG (LV-ECoG) was also measured after phentolamine treatment. These effects of phentolamine persisted during hypoxia. 3. In group II fetuses a pronounced decrease in the incidence of FBM occurred after administration of prazosin following either phentolamine or saline pretreatment. These effects of prazosin on FBM were independent of an effect on ECoG activity. 4. We conclude that catecholamines have a stimulatory role on FBM mediated via an alpha 1-adrenoreceptor mechanism. Phentolamine leads to an increase in FBM by preferentially antagonizing presynaptic alpha 2-adrenoreceptors over postsynaptic alpha 1-adrenoreceptors. This influence of phentolamine on FBM may be secondary to its effect on ECoG. Promotion of LV-ECoG by catecholamines is mediated via an alpha 1-independent mechanism.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1987

Phentolamine reverses NPY-induced inhibition of insulin secretion in isolated rat islets.

It has been shown that the rodent pancreas is innervated by neuropeptide Y (NPY) nerves, some of which are adrenergic, and that NPY inhibits glucose-induced insulin secretion in vivo in the mouse and that from isolated rat islets in vitro. We now investigated whether the alpha-adrenoceptor antagonist phentolamine affects the inhibitory action of NPY on insulin secretion from isolated rat islets. It was found that NPY dose dependently inhibited insulin secretion stimulated by glucose (11.1 mM). At a concentration of 10(-7) M, NPY totally abolished the insulin secretory response to glucose. It was also found that incubation with the alpha-adrenoceptor antagonist phentolamine (10(-6) M) itself enhanced the insulin secretion at 3.3 mM but not at 16.7 mM glucose. Moreover, phentolamine counteracted the inhibitory action of NPY. Thus, at 10(-8) M, NPY could no longer inhibit insulin secretion when phentolamine (10(-6) M) was present, whether 3.3 mM or 11.1 mM glucose was present. In contrast, somatostatin (10(-7) M) could inhibit insulin secretion, both in the presence and absence of phentolamine (10(-6) M); this showed that phentolamine does not reverse all types of inhibition. However, when the dose of phentolamine was decreased to 10(-7) M, the inhibitory action of NPY on glucose-induced insulin secretion was retained indicating that the reversal of the NPY effect by phentolamine is a competitive effect. It is concluded that NPY inhibits glucose-induced insulin secretion by a direct action on the islets, and that phentolamine reverses this inhibitory action of NPY in a competitive manner.

Animals↗
PubMed2000

Alpha-adrenergic receptor blockade by phentolamine increases the efficacy of vasodilators in penile corpus cavernosum.

Penile trabecular smooth muscle tone, a major determinant of erectile function, is highly regulated by numerous inter- and intracellular pathways. The interaction between pathways mediating contraction and relaxation has not been studied in detail. To this end, we investigated the functional effects of alpha adrenergic receptor blockade with phentolamine and its interaction with vasodilators (sildenafil, vasoactive intestinal polypeptide (VIP) and PGE1) that elevate cyclic nucleotides on penile cavernosal smooth muscle contractility. In organ bath preparations of cavernosal tissue strips contracted with phenylephrine, phentolamine significantly enhanced relaxation induced by sildenafil, VIP and PGE1. Sildenafil, VIP or PGE1 also significantly enhanced relaxation induced by phentolamine in cavernosal tissue strips contracted with phenylephrine. To study the effects of alpha adrenergic receptor blockade and modification of cyclic nucleotide metabolism during active neurogenic input, cavernosal tissue strips in organ bath preparations were contracted with the non-adrenergic agonist endothelin-1 and subjected to electrical field stimulation (EFS) in the absence or presence of phentolamine and/or sildenafil. EFS (5-40Hz) typically caused biphasic relaxation and contraction responses. Phentolamine alone enhanced relaxation and reduced or prevented contraction to EFS. Sildenafil enhanced relaxation to EFS at lower frequencies (< or = 5 Hz). The combination of phentolamine and sildenafil enhanced EFS-induced relaxation at all frequencies tested. EFS, in the presence of 10 nM phentolamine and 30 nM sildenafil, produced enhanced relaxation responses which were quantitatively similar to those obtained in the presence of 50 nM sildenafil alone. Thus, blockade of alpha-adrenergic receptors with phentolamine increases the efficacy of cyclic nucleotide-dependent vasodilators. Furthermore, phentolamine potentiates relaxation and attenuates contraction in response to endogenous neurotransmitters which are released during EFS. These findings suggest that antagonism of alpha-adrenergic signaling enables other independent relaxatory pathways to predominate within penile trabecular smooth muscle.

Adrenergic alpha-Antagonists↗
PubMed1984

Phentolamine-induced rhythmic contractions in bladder detrusor muscle of guinea-pig.

Phentolamine caused a rhythmic contraction concentration-dependently without affecting resting tone in the detrusor muscle. Prazosin, yohimbine, propranolol, noradrenaline, clonidine or isoprenaline failed to cause the rhythmic contraction. These agents did not modify the response to phentolamine suggesting no involvement of alpha- or beta-adrenoceptors in the response to phentolamine. Chlorpheniramine, cimetidine, methysergide, SK&F 83566, atropine, bretylium, hemicholinium or tetrodotoxin failed to inhibit the response to phentolamine. These results suggest that the effect of phentolamine is not mediated through histaminergic, 5-hydroxytryptaminergic, dopaminergic or cholinergic systems, or through transmitter release from nerve endings. Prostaglandin F2 alpha (PGF2 alpha), arachidonic acid but not ATP caused rhythmic contractions which resembled the response to phentolamine. Potassium also caused a contraction with increasing resting tone. Following treatment with nifedipine, or incubation in a Ca2+-free medium, the responses to phentolamine, PGF2 alpha, arachidonic acid and potassium were markedly inhibited or abolished. Cyclo-oxygenase inhibitors such as indomethacin, aspirin and corticosterone inhibited or abolished the responses to phentolamine and arachidonic acid but did not inhibit the response to PGF2 alpha. The results suggest that the phentolamine-induced rhythmic contraction may, at least in part, result from the cyclo-oxygenase metabolite of arachidonic acid in guinea-pig detrusor muscles and a consequent increase in the transmembrane Ca2+-influx.

Animals↗
PubMed1989

Phentolamine blocks presynaptic serotonin autoreceptors in rabbit and rat brain cortex.

Possible antagonist effects of phentolamine at presynaptic serotonin autoreceptors were studied in slices of the occipito-parietal cortices of the rabbit and the rat. The slices were preincubated with 3H-serotonin and then superfused and stimulated electrically with single pulses or pulse trains. Nitroquipazine 1 mumol/l, a compound that inhibits the high affinity neuronal uptake of serotonin, was present in the superfusion medium in all one pulse-experiments as well as in experiments in which the effect of unlabelled serotonin was examined. In rabbit cortical slices, unlabelled serotonin reduced the single pulse-evoked overflow of tritium. Its concentration-response curve was not changed by the selective alpha 2-adrenoceptor antagonist idazoxan 1 mumol/l but was shifted to the right by phentolamine 1 and 10 mumol/l. Phentolamine 10 mumol/l also shifted to the right the concentration-inhibition curve of the selective 5-HT1-receptor agonist 5-carboxamidotryptamine. When the slices were stimulated by trains of 30 pulses at 3 Hz, phentolamine 1 and 10 mumol/l but not 0.1 mumol/l increased the evoked overflow of tritium, the maximal increase amounting to 178%; its effect was enhanced in the presence of nitroquipazine 1 mumol/l plus idazoxan 10 mumol/l (a drug combination that, when given alone, slightly increased the evoked overflow of tritium). The serotonin receptor antagonist metitepin at concentrations of 0.01-1 mumol/l also increased the overflow of tritium elicited by 30 pulses/3 Hz, the maximal increase amounting to 280%; its effect was potentiated in the presence of nitroquipazine 1 mumol/l plus idazoxan 10 mumol/l but was abolished or almost abolished in the presence of nitroquipazine 1 mumol/l plus phentolamine 10 mumol/l (a drug combination that, given alone, greatly increased the evoked overflow of tritium). When slices were stimulated by trains of 360 pulses at 3 Hz, there was no apparent antagonism of phentolamine 10 mumol/l against the inhibitory effect of unlabelled serotonin. In rat brain cortex slices, unlabelled serotonin reduced the overflow of tritium elicited by 4 pulses delivered at 100 Hz. Again, phentolamine 10 mumol/l shifted the concentration-response curve to the right. It is concluded that phentolamine blocks presynaptic serotonin autoreceptors in rabbit and rat brain cortex with pA2 values of 6.44 and 5.95, respectively. Previous failures to detect the antagonistic effect against exogenous agonists were probably due to stimulation conditions that led to marked endogenous autoinhibition of serotonin release.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1975

Biphasic effect of the alpha-adrenolytic phentolamine on hormone-stimulated formation of cyclic adenosine-3',5'-monophosphate in isolated fat cells of rats.

Isolated fat cells from rat epididymal adipose tissue were incubated with various lipolytic hormones in the absence and presence of the alpha-adrenergic blocking agent phentolamine. Lipolysis, stimulated by noradrenaline, isoproterenol, or ACTH, was inhibited dose-dependently by phentolamine. At concentrations of phentolamine where lipolysis was already inhibited, phentolamine had a biphasic effect on hormone-stimulated formation of cAMP. Low concentrations of phentolamine enhanced cAMP formation, while high concentrations inhibited cAMP. The additional increase of cAMP formation by phentolamine was only seen with maximally effective concentrations of noradrenaline, isoproterenol, and ACTH. Half-maximally effective concentrations were invariably inhibited by phentolamine. The activity of noradrenaline-stimulated adenylate cyclase of fat-cell plasma membranes was inhibited by phentolamine, whereas cAMP phosphodiesterase activity was unaffected.

Adipose Tissue↗
PubMed1992

Objective double-blind evaluation of erectile function with intracorporeal papaverine in combination with phentolamine and/or prostaglandin E1.

We performed a double-blind, crossover study using objective measurements to compare maximum rigidity and duration of erections with papaverine hydrochloride in combination with phentolamine mesylate and/or prostaglandin E1. The rationale for the protocol was to combine a smooth muscle relaxant (papaverine) with either or both vasodilating agents (phentolamine and prostaglandin E1) commonly used for injection therapy. The 7 volunteer patients with organic impotence documented by abnormal nocturnal penile tumescence testing were injected with 0.5 to 1.0 ml. papaverine (30 mg./ml.) in combination with phentolamine (0.5 mg./ml.) and/or prostaglandin E1 (5 micrograms./ml.). Each patient received 2 injections on each of 2 testing dates; injection 2 was given after tumescence resulting from injection 1 had subsided completely. The medications were given in a randomized, counterbalanced order following double-blind procedures. Patients evaluated the erections subjectively. In addition, the RigiScan device was used to measure maximum rigidity and duration of erections. All patients observed increased duration of erections with both combinations containing prostaglandin E1. Analysis of RigiScan measurements showed no statistically significant differences for maximum rigidity (p greater than 0.1) but significantly greater duration of erections with papaverine plus prostaglandin E1, and papaverine plus phentolamine plus prostaglandin E1 compared to papaverine plus phentolamine (p less than 0.001). There was no statistical difference in rigidity or duration of erections between papaverine plus prostaglandin E1 and papaverine plus phentolamine plus prostaglandin E1. No patient reported significant penile pain with any of the injections. We conclude that the combination of papaverine and prostaglandin E1 produces erections of longer duration than papaverine plus phentolamine and that no additional benefit is gained by adding phentolamine to a combination of papaverine and prostaglandin E1. Further studies are in progress to define optimal dose response curves for papaverine and prostaglandin E1 as individual agents and in combination.

Alprostadil↗
PubMed1998

Phentolamine mesylate relaxes penile corpus cavernosum tissue by adrenergic and non-adrenergic mechanisms.

AIM OF THE STUDY: We investigated the biochemical and physiological mechanisms of action of phentolamine mesylate (Vasomax) in regulating erectile tissue smooth muscle contractility in human and rabbit corpus cavernosum. METHODS: The binding activity of phentolamine was investigated in a cell-free system by displacement of specific and selective radiolabelled ligands to alpha 1 and 2 adrenergic receptors. The physiologic activity of phentolamine-mediated relaxation of adrenergic and non-adrenergic pre-contracted erectile tissue strips of human and rabbit corpus cavernosum were studied in organ bath chambers. RESULTS: In corpus cavernosum membranes, phentolamine displaced binding of the selective alpha 1 receptor antagonists [125I]HEAT and [3H]prazosin and the alpha 2 receptor antagonists [3H]rauwolscine and [3H]RX 821002 with relatively high affinity. Phentolamine caused concentration dependent relaxation in erectile tissue strips pre-contracted with adrenergic agonists phenylephrine, norepinephrine, oxymetazoline and UK 14,304, as well as with non-adrenergic contractile agents endothelin and KCl. Biochemical and physiologic studies reveal that the concentration of phentolamine required to displace half maximal binding or to produce half-maximal relaxation was similar to that found in human plasma 30 min after ingestion of 40 mg of Vasomax. Reversible inhibition of nitric oxide synthase by L-nitroarginine or mechanical disruption of endothelium diminished non-adrenergic phentolamine-mediated erectile tissue relaxation. CONCLUSIONS: Phentolamine mesylate induced relaxation of corpus cavernosum erectile tissue by direct antagonism of alpha 1 and 2 adrenergic receptors and by indirect functional antagonism via a non-adrenergic, endothelium-mediated mechanism suggesting nitric oxide synthase activation.

Adrenergic alpha-Agonists↗