vasoactive-intestinal-peptide and Erectile-Dysfunction

Data assessing the effectiveness of intracavernosal injections (ICIs) for the treatment of erectile dysfunction (ED) are limited. This study evaluates intracavernosal injectable therapies for ED and reviews available guidelines that inform clinical practice.. A systematic search using electronic databases (Medline, Pubmed) was performed for studies investigating injectable management strategies for ED published after 1990. Primary outcome measures were to comparatively evaluate clinical efficacy, continuation rates and adverse event profiles of each injectable agent as monotherapy or in combination. The secondary outcome measurement was to discuss available guidelines that inform clinical practice for injectable agents.. ICIs demonstrate clinical efficacy in 54-100% of patients, early discontinuation rates of ≤ 38% and adverse events in ≤ 26%. Discontinuation rates are typically greatest within 3-6 months of commencement. Anxiety related to the initial injection occurs in approximately 65% and anxiety levels can remain high for 4 months. Approval of intracavernosal injection agents is mainly limited to alprostadil with the recent addition of aviptadil/phentolamine combination therapy in a select few geographical regions. Although combination therapies are attractive alternative options, their formulations are variable and should be standardised before widespread acceptance is achieved.. ICIs are associated with good clinical efficacy rates, high discontinuation rates and a moderate side-effect profile. They represent an important tool in the urological armamentarium for treating ED in patients that cannot tolerate or are refractory to oral therapies.

Topics: Alprostadil; Drug Combinations; Erectile Dysfunction; Humans; Injections, Intralesional; Male; Penis; Phentolamine; Vasoactive Intestinal Peptide; Vasodilator Agents

Erectile dysfunction (ED) is becoming an increasingly common problem and although oral therapies offer first-line treatment for many men, they are contraindicated or ineffective in substantial groups of patients. Intracavernosal injection (ICI) therapy is the most effective nonsurgical treatment for ED and offers an effective alternative to oral therapy. Sufficient arterial blood supply and a functional veno-occlusive mechanism are prerequisites in the attainment and maintenance of a functional erection. Invicorp (Plethora Solutions, London, UK) is a combination of vasoactive intestinal polypeptide (VIP) 25 microg and phentolamine mesylate 1 or 2 mg for ICI in the management of moderate to severe ED. The two active components have complementary modes of action; VIP has a potent effect on the veno-occlusive mechanism, but little effect on arterial inflow, whereas phentolamine increases arterial blood flow with no effect on the veno-occlusive mechanism. Clinical studies showed that Invicorp is effective in >or=80% of men with ED, including those who have failed to respond to other therapies and, unlike existing intracavernosal therapies, is associated with a very low incidence of penile pain and virtually negligible risk of priapism. We estimate that there are >5.9 million men in the USA alone for whom oral ED drugs are not a viable treatment option, and for whom Invicorp might offer a safe and effective alternative.

Topics: Aged; Drug Combinations; Erectile Dysfunction; Humans; Injections; Male; Middle Aged; Patient Satisfaction; Penile Erection; Phentolamine; Risk Factors; Severity of Illness Index; Treatment Outcome; Vasoactive Intestinal Peptide

Erectile dysfunction (ED) reduces the quality of life. It is estimated that 52% of men have some degree of ED, which is associated with ageing. While it is clear that there are a variety of current treatment options for ED, each of these has drawbacks and contraindications. A better understanding of the physiological mechanisms involved in penile erection will provide new ways to treat ED. This review not only focuses on the vasoconstrictors and vasodilators that control the state of contraction and relaxation of the corpora cavernosa smooth muscle, but also presents a novel Ca(2+)-sensitising pathway that contributes to maintaining the penis in the non-erect state. Studies have shown that inhibition of the RhoA/Rho-kinase signalling pathway induces penile erection. Further understanding of this RhoA/Rho-kinase pathway may provide a novel alternative treatment for ED.

Topics: Adrenergic Agonists; Adult; Aged; Aging; Amides; Angiotensin II; Calcium Signaling; Cyclic AMP; Endothelin-1; Erectile Dysfunction; Forecasting; Humans; Intracellular Signaling Peptides and Proteins; Male; Middle Aged; Muscle Contraction; Muscle, Smooth; Nitric Oxide; Penis; Protein Serine-Threonine Kinases; Pyridines; rho-Associated Kinases; rhoA GTP-Binding Protein; Vasoactive Intestinal Peptide

Topics: Animals; Erectile Dysfunction; Humans; Male; Muscle, Smooth; Penis; Rats; Vasoactive Intestinal Peptide

Central regulation of the erectile process involves several transmitters, including dopamine, serotonin, noradrenaline, and nitric oxide, and peptides, such as oxytocin and ACTH/alpha-MSH. These systems may be targets for future drugs designed to treat erectile dysfunction. Peripherally, the different steps involved in neurotransmission, impulse propagation, and intracellular transduction of neural signals in penile smooth muscles need further investigation. Continued studies of the interactions between different transmitters/modulators may reveal new combination therapies. Increased knowledge of the changes in penile tissues associated with erectile dysfunction may explain the pathogenetic mechanisms and help to prevent the disorder.

Topics: Animals; Apomorphine; Dopamine Agonists; Endothelins; Erectile Dysfunction; Humans; Male; Penile Erection; Receptors, Adrenergic; Receptors, Dopamine; Receptors, Endothelin; Selective Serotonin Reuptake Inhibitors; Trazodone; Vasoactive Intestinal Peptide

Aviptadil is an injectable formulation of vasoactive intestinal polypeptide (VIP) in combination with the adrenergic drug phentolamine. Aviptadil in combination with phentolamine and sexual stimulation, is expected to provide a new and effective alternative for erectile dysfunction (ED) patients that is essentially free of the troublesome side effects and cumbersome delivery methods which limit the use of other pharmacologic preparations. Aviptadil can be delivered using Senetek's novel and patented autoinjector (Reliaject), which renders the self-injection process exceptionally easy, unobtrusive to perform and helps ensure accurate, safe delivery of the medication [306380]. In July 1997, Senetek filed a PLA with the Danish Medicines Authority [253591] and its third PLA in Ireland for the treatment of moderate-to-severe, organic-based ED [255084]. In September 1997, Senetek filed PLAs seeking approval to market aviptadil in Switzerland, South Africa and New Zealand 1263505]; by April 2000, it had been approved in New Zealand [361039]. All clinical trials were placed on hold in August 1999 after the FDA advised the MCA of safety concerns regarding a competitor's phentolamine mesylate product (Vasomax; Zonagen Inc/Schering-Plough Corp). At this time, the activities to support the registration of aviptadil in the EU were ongoing and were not impacted by the clinical hold [336510]. In March 2000, after review by an independent clinical pharmacotoxicologist company employed by Senetek, the carcinogenicity observed in animal models was deemed to have no relevance as an indicator of carcinogenic risk in humans. This information was passed to the MCA along with an extensive review of all prior company studies and the medical literature supporting the efficacy and safety of phentolamine mesylate [361039]. In July 2000, the FDA upgraded the status of the aviptadil IND to a partial clinical hold, allowing human studies to be conducted in the US with a limited duration of 3 months and total number of doses not exceeding three per week. The FDA also recommended that Senetek conduct a two-year rodent study of aviptadil as a result of previously reported brown adipose tissue proliferations observed in the course of a competitor's rodent study in which phentolamine mesylate was administered daily [373086]. In August 2000, the MCA lifted the hold on trials stating the findings do not represent a significant carcinogenic risk in man [378615]. In October 2000, marketing app

Topics: Clinical Trials as Topic; Drug Combinations; Erectile Dysfunction; Humans; Male; Phentolamine; Vasoactive Intestinal Peptide

Topics: Alprostadil; Calcitonin Gene-Related Peptide; Chlorpromazine; Dose-Response Relationship, Drug; Erectile Dysfunction; Humans; Injections; Male; Moxisylyte; Papaverine; Patient Satisfaction; Phentolamine; Self Administration; Sympatholytics; Treatment Outcome; Vasoactive Intestinal Peptide; Vasodilator Agents

Topics: Animals; Behavior, Animal; Central Nervous System; Drug Design; Erectile Dysfunction; Humans; Male; Mammals; Motor Activity; Periodicity; Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; Receptors, Pituitary Hormone; Receptors, Vasoactive Intestinal Peptide; Sexual Behavior, Animal; Substrate Specificity; Vasoactive Intestinal Peptide

Topics: Alprostadil; Androgens; Attitude to Health; Erectile Dysfunction; Humans; Male; Papaverine; Penile Prosthesis; Sex Counseling; Trazodone; Vasoactive Intestinal Peptide; Yohimbine

From the beginning of the eighties papaverine was well established as the drug of choice for diagnosis and management of vasculogenic impotence. In the second half of the eighties decade many authors referred on experimental use of PGE1 in erection disease. PGE1 has been showed a safe and effectiveness drug. During the period September 1989-October 1990 at our Institution 98 pts. with erectile disorders were managed by I.C.I. with PGE1. Out of 98 cases 88 had success. Prolonged erection occurred in 4 pts. (4.2%). 10 pts. showed only tumescence. So there are been treated by I.C.I. with combined papaverine and PGE1 with better results. No side effects were formed in 10 pts. managed by self-injection of PGE1.

Topics: Alprostadil; Erectile Dysfunction; Humans; Injections; Ketanserin; Male; Papaverine; Penile Erection; Penis; Phentolamine; Vasoactive Intestinal Peptide; Vasodilator Agents; Yohimbine

This paper reviews the intrapenile control of erection and the principal pathophysiological and therapeutic implications (especially intracavernous injections) of these physiological data. The regulation of flaccidity is fairly well known. This principally results from a continuous adrenergic discharge responsible, via activation of the alpha receptors, for tonic contraction of the smooth muscle fibres (SMF) of the corpora cavernosa (CC), preventing blood from entering the spaces of the CC. The complementary role of serotonin, histamine, prostaglandins (PG) F1 and F2 alpha and neuropeptide Y is still unclear. The regulation of erection is less well understood. The principal phenomenon is probably inhibition of the anti-erectile alpha adrenergic tone, allowing relaxation of the SMF and congestion of the areolae of the CC, influx of arterial blood and occlusion of the venous exits. However, an additional relaxing nervous stimulation may also be required. The modulation of anti-erectile adrenergic activity could be the result of Vasoactive-Intestinal-Polypeptide which, however, is unable to induce complete erection on its own, and/or PGE1. Acetylcholine, whose role is still unclear, stimulation of beta adrenergic receptors and presynaptic alpha-2 receptors, histamine, a relaxant factor of endothelial origin and possibly other neurotransmitters as yet unidentified, may also be involved.

Topics: Alprostadil; Erectile Dysfunction; Humans; Male; Penile Erection; Penis; Sympathomimetics; Synaptic Transmission; Vasoactive Intestinal Peptide

Topics: Adrenocorticotropic Hormone; Adult; Diabetes Complications; Diabetes Mellitus; Diabetic Angiopathies; Diabetic Neuropathies; Erectile Dysfunction; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Infertility; Luteinizing Hormone; Male; Melanocyte-Stimulating Hormones; Middle Aged; Prolactin; Reproduction; Sexual Dysfunction, Physiological; Thyrotropin-Releasing Hormone; Urodynamics; Vasoactive Intestinal Peptide

To compare two injectable treatments, alprostadil 5-20 microg powder for injection and a combination of vasoactive intestinal polypeptide (VIP) and phentolamine in patients with erectile dysfunction (ED).. This was an open multicentre, randomised crossover study comprising two phases. The first phase established the dose of each drug required to produce an erection suitable for sexual intercourse (grade 3 erection). In phase 2, responders to both drugs received, in random order, four doses of VIP/phentolamine, presented as ampoules, and four doses of alprostadil, presented as powder for injection. This was followed by four doses of VIP/phentolamine, presented in an autoinjector. In both phases, patient preference was assessed for each preparation.. 187 patients were recruited. In the first phase, both treatments were effective, (83% alprostadil vs. 73% VIP/phentolamine, p = 0.002) but more patients preferred VIP/phentolamine (69 vs. 31%, p = 0.011). In phase 2 (n = 107), the proportion of injections that produced a grade 3 erection was similar for all three treatments (83-85%), but both presentations of VIP/phentolamine (ampoule and auto-injector) were preferred by significantly more patients (p < 0.001). Compared with both presentations of VIP/phentolamine, alprostadil produced a higher frequency of pain (28% of injections vs. 3% for each VIP/phentolamine presentation; p < 0.001) and a lower frequency of facial flushing (3 vs. 16-17%; p < 0.001).. VIP/phentolamine and alprostadil were effective treatments for ED, however the VIP/phentolamine combination was preferred by more patients, which may be because it was much less likely to cause pain.

Topics: Adult; Aged; Alprostadil; Cross-Over Studies; Drug Therapy, Combination; Erectile Dysfunction; Humans; Injections; Male; Middle Aged; Phentolamine; Treatment Outcome; Vasoactive Intestinal Peptide

Three hundred and four patients with non-psychogenic erectile dysfunction (ED) completed a dose assessment phase with intracavernosal injection utilizing 25 micrograms vasoactive intestinal polypeptide (VIP) combined with phentolamine mesylate 1.0 mg (VIP/P-1) or 2.0 mg (VIP/P-2) in an auto-injector for a response rate of 83.9%. In a sub-group of 183 patients who withdrew from one or more previous ED therapies, 82% responded with an erection suitable for intercourse. One hundred and ninety-five patients were subsequently treated in a placebo controlled phase. 75.1% responded to VIP/P-1, 12% to placebo (P < 0.001); 66.5% responded to VIP/P-2, 10.3% to placebo (P < 0.001), with the median duration of erection of 54 min. The principal adverse event was transient facial flushing in 2770 injections (33.9%). There was no pain post injection and two episodes of priapism (0.05%). Only nine patients withdrew because of adverse events. Over 85% and 95% of patients were satisfied with the drug and auto-injector, respectively. Over 81% of patients and 76% of partners reported an improved quality of life.

Topics: Adult; Aged; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Erectile Dysfunction; Humans; Injections; Male; Middle Aged; Phentolamine; Placebos; Vasoactive Intestinal Peptide; Vasodilator Agents

A double-blind, placebo-controlled clinical trial of the intracavernous injection of vasoactive intestinal peptide was conducted and studied in 24 men with erectile dysfunction of diabetic, neurogenic and psychogenic etiology. The patients were randomized into 6 groups of 4 subjects each and received either placebo, or 200 or 400 pmol. vasoactive intestinal peptide at each of 3 consecutive weekly visits. An increase in penile length was associated significantly with treatment (F equals 5.10, p equals 0.01), dose-related, and independent of the time and sequence of treatment. An increase in penile diameter was associated significantly with treatment (F equals 8.14, p equals 0.001) and time (F equals 8.14, p equals 0.001), dose-related and independent of the sequence of treatment. Penile rigidity was associated significantly with time (F equals 5.44, p equals 0.008), associated nearly significantly with treatment (F equals 3.11, p equals 0.056) and independent of sequence of treatment. Despite some measurable treatment-related increase none of the patients achieved penile rigidity adequate for intromission.

Topics: Adult; Aged; Dose-Response Relationship, Drug; Double-Blind Method; Erectile Dysfunction; Humans; Male; Middle Aged; Penile Erection; Randomized Controlled Trials as Topic; Vasoactive Intestinal Peptide

To determine the expressions of calcitonin gene-related peptide (CGRP) and vasoactive intestinal peptide (VIP) in the penile tissue of the ED rat model and explore their action mechanisms.. An ED model was established in 44 mature male SD rats by feeding them on a spinach + coriander diet in a cold-wet environment and another 10 were taken as normal controls. Then the model rats were randomly divided into an ED model control group (n = 15) treated by gavage of distilled water in the same modeling environment, a spontaneous recovery group (n = 15) treated by gavage of distilled water in the normal environment, and a medication group (n = 14) treated intragastrically with Yimusake Tablets at 250 mg/kg qd. After 2－3 weeks of intervention, the expressions of CGRP and VIP in the penile tissue were detected by immunohistochemistry and Western blot.. Immunohistochemistry showed that, after 2 weeks of intervention, both the expressions of CGRP and VIP in the rat penile tissue were significantly lower in the ED model control (150.0 ± 43.3 and 36.4 ± 13.1) and the spontaneous recovery group (165.9 ± 40.7 and 67.5 ± 29.0) than in the normal control (227.3 ± 42.5 and 175.0 ± 45.6) (P < 0.05), but remarkably higher in the medication group (255.0 ± 38.7 and 167.5 ± 42.6) than those in the ED model control and spontaneous recovery groups (P < 0.05).. The expressions of CGRP and VIP were significantly down-regulated in the ED rat model, and Yimusake Tablets improved ED by up-regulating their expressions.

Topics: Animals; Calcitonin; Calcitonin Gene-Related Peptide; Down-Regulation; Erectile Dysfunction; Male; Medicine, Chinese Traditional; Penis; Rats; Rats, Sprague-Dawley; Vasoactive Intestinal Peptide

Topics: Drug Combinations; Drug Design; Erectile Dysfunction; Humans; Male; Phentolamine; Phosphodiesterase 5 Inhibitors; Vasoactive Intestinal Peptide

To determine the feasibility of transfecting penile corpora cavernosa with pcDNA3/vasoactive intestinal polypeptide (VIP) cDNA, which encodes for VIP in streptozotocin (STZ)-diabetic rats, to clarify whether transfection of VIP cDNA into the cavernosum affects the physiological response to cavernosal nerve stimulation, and whether this process would affect other organs in the diabetic rat model in vivo.. pcDNA3/VIP cDNA was injected into the corpus cavernosum of STZ-induced diabetic Sprague-Dawley rats. The intracavernosal pressure (ICP) and response to electrical stimulation of the cavernosal nerve (15 Hz, 1.5 ms, 20 V, 1 min) were measured in subsamples of rats at 1, 3, 7 and 14 days after injection; after measuring the ICP the animals were killed, and penile, hepatic, renal artery and abdominal aorta tissue samples were frozen in liquid nitrogen and stored at -80 degrees C. The gene expression of VIP in all samples, assessed as the expression of VIP mRNA, was estimated using a semiquantitative reverse-transcription polymerase chain reaction.. The mean amplitude of ICP and expression of VIP mRNA in the cavernosa of the VIP-treated rats was greater at 1, 3, 7 and 14 days after injection (P < 0.05) than in the control animals. There were no changes in the expression of VIP mRNA in hepatic, renal and abdominal aorta samples after injection (P > 0.05).. VIP cDNA is easily incorporated into corpus cavernosum, and the expression is sustained for > or = 2 weeks in the penis in vivo. The transfer of VIP is capable of altering the physiologically relevant erectile response, as measured by an increase in the ICP after stimulating the cavernosal nerve. The intracorporal micro-injection of pcDNA3/VIP cDNA had little effect on the expression of VIP mRNA in other important organs.

Topics: Animals; Diabetes Mellitus, Experimental; Erectile Dysfunction; Feasibility Studies; Gene Transfer Techniques; Genetic Therapy; Male; Penile Erection; Rats; Rats, Sprague-Dawley; Vasoactive Intestinal Peptide

Vasoactive intestinal polypeptide (VIP) is a potent vasodilator and smooth muscle relaxant, and also fulfils several of the criteria for a neurotransmitter mediating penile erection. VIP donor and gene transfer of VIP are a potentially promising and physiologically relevant strategies for the treatment of erectile dysfunction.

Topics: Animals; Cattle; Dogs; Erectile Dysfunction; Gene Transfer Techniques; Humans; Male; Penile Erection; Rats; Vasoactive Intestinal Peptide

The generation of nitric oxide (NO) in penile erectile tissue and the subsequent elevation of cyclic GMP (cGMP) levels are important for normal penile erection. Current treatments of erectile dysfunction elevate either cGMP levels by blocking cGMP degrading phosphodiesterase 5 or cyclic AMP (cAMP) levels by intrapenile injection of prostaglandin E1. The molecular target or targets of cGMP in erectile tissue and the role of cAMP for normal penile erection are not known. Herein, we report that mice lacking cGMP-dependent kinase I (cGKI) have a very low ability to reproduce and that their corpora cavernosa fail to relax on activation of the NO/cGMP signaling cascade. Elevation of cAMP by forskolin, however, induces similar relaxation in normal and cGKI-null corpus cavernosum. In addition, sperm derived from cGKI-null mice is normal, can undergo acrosomal reactions, and can efficiently fertilize eggs. Altogether, these data identify cGKI as the downstream target of cGMP in erectile tissue and provide evidence that cAMP signaling cannot compensate for the absence of the cGMP/cGKI signaling cascade in vivo.

Topics: Animals; Carrier Proteins; Cyclic GMP-Dependent Protein Kinases; Erectile Dysfunction; Female; Fertilization in Vitro; Humans; Immunohistochemistry; Male; Membrane Transport Proteins; Mice; Mice, Knockout; Muscle Contraction; Muscle, Smooth; Nitric Oxide Synthase; Nitric Oxide Synthase Type I; Penile Erection; Penis; Thiolester Hydrolases; Tyrosine 3-Monooxygenase; Ubiquitin Thiolesterase; Vasoactive Intestinal Peptide; Vesicular Acetylcholine Transport Proteins; Vesicular Transport Proteins

In vitro and in vivo studies were performed to determine the potential use of tamsulosin (TAM) versus phentolamine (PHE) for intracavernosal injection (ICI) therapy when mixed with papaverine (PAP) and/or prostagladin E1 (PGE1) or with vasoactive intestinal polypeptide (VIP) for the treatment of erectile dysfunction. We performed isometric tension studies on rabbit (n = 15), dog (n = 5), and human (n = 10) cavernous smooth muscle strips with TAM, PAP, PHE, VIP, PGE1, and the combinations of PAP and PHE; PAP and TAM; VIP and PHE; VIP and TAM; PAP, PGE1 and PHE; and PAP, PGE1 and TAM. TAM-containing trimix (PAP 18.75 mg, PGE1 6.25 micromg, and TAM 0.875 mg per ml) or PHE-containing trimix (PAP, PGE1, and PHE 0.625 mg per ml) were also injected into the cavernous bodies of ten mongrel dogs. Among the single agents, TAM and PGE1 (only in human) had the strongest effect on the relaxation of cavernous muscles in rabbit, dog, and human strips (P<0.05). Relaxation responses to 2- or 3-drug mixtures containing tamsulosin were also significantly better (P<0.05) than PHE-containing ones in rabbit, dog, and human strips. The increase in intracavernosal pressure with a TAM-containing trimix was higher than with a PHE-containing one (0.03 ml; 81.2 vs. 75.8 mm Hg, 0.04 ml; 103.2 vs. 94.3 mm Hg), although not statistically different. The drop in systemic blood pressure was lower after injection of a TAM-containing trimix than a PHE-containing one, although not statistically different. In conclusion, tamsulosin might be a more efficacious and safer agent to use for ICI therapy than phentolamine.

Topics: Adrenergic alpha-Antagonists; Alprostadil; Animals; Blood Pressure; Dogs; Drug Synergism; Erectile Dysfunction; Humans; In Vitro Techniques; Injections; Male; Middle Aged; Muscle Relaxation; Muscle, Smooth; Papaverine; Penile Erection; Phentolamine; Rabbits; Sulfonamides; Tamsulosin; Vasoactive Intestinal Peptide

Topics: Clinical Trials as Topic; Drug Combinations; Erectile Dysfunction; Humans; Male; Middle Aged; Phentolamine; Vasoactive Intestinal Peptide

To study the effect of vasoactive intestinal polypeptide (VIP) and phentolamine mesylate (PM) on patients in whom previous intracavernosal therapy had failed.. The study comprised 70 consecutive patients attending a clinic for erectile dysfunction, in whom previous therapy with intracavernosal prostaglandin-E1 (20 microg and papaverine (30 mg) combined with 1 mg PM had failed. They were given intracavernosal injections, initially with 25 microg VIP/1 mg PM (VIP1) and if unsuccessful, 25 microg VIP/2 mg PM (VIP2). Both VIP1 and VIP2 were administered using a pre-filled ready-to-use autoinjector fitted with a 29 G needle. The patients were diagnosed as having spinal cord lesion (eight), diabetes (21), ischaemic heart disease (12), hypertension (six), other diagnoses (nine), or idiopathic causes (14).. Forty-seven (67%) of patients achieved erections sufficient for sexual intercourse (33 on VIP1 and 14 on VIP2), initially under clinical supervision and subsequently during home use. Minor side-effects were transient facial flushing in 37 (53%), truncal flushing in six (9%), bruising in 14 (20%) and pain from the injection needle in eight (11%). No patients reported priapism or other serious adverse events.. The combination of VIP and PM at the dose used was a safe and effective treatment in patients in whom other therapies had failed.

Topics: Adolescent; Adult; Aged; Drug Combinations; Erectile Dysfunction; Humans; Injections; Male; Middle Aged; Phentolamine; Sympatholytics; Syringes; Vasoactive Intestinal Peptide

Twenty men with chronic impotence with a mean age of 46 years (range 26-63 y) were treated with self administration of 0.35 ml of Vasopotin 1 and 2, a combination of 30 mg Vasoactive Intestinal Peptide (VIP) and either 1.0 or 2.0 mg Phentolamine Mesylate. All patient were assessed using a standard protocol which included history and examination, vibratory penile biothesiometry, colour flow duplex Doppler ultrasonography and where indicated, Rigiscan nocturnal penile tumescence testing, dynamic infusion cavernosometry and cavernosography (DICC) and angiography. Impotence was classified as psychogenic in six patients, arteriogenic in nine patients, neurogenic in two patients and cavernosal venous leakage in three patients. A total of 60 injections was given. After sexual stimulation, an erection of sufficient rigidity for intercourse occurred in six patients with psychogenic impotence, seven of the nine patients with arteriogenic impotence, two patients with neurogenic impotence and one of three patients with cavernosal venous leakage. No patients experienced priapism, two patients complained of postinjection penile pain and three patients experienced transient facial flushing. Intracavernous self injection of Vasopotin appears to be a useful treatment for erectile dysfunction.

Topics: Adult; Erectile Dysfunction; Humans; Impotence, Vasculogenic; Male; Middle Aged; Penile Erection; Penis; Phentolamine; Pilot Projects; Prospective Studies; Vasoactive Intestinal Peptide; Vasodilator Agents

In this work the Authors speak about topical treatment in diagnosis and therapy of erectile deficit with prostaglandin, papaverine, phentolamine, V.I.P., nitroglycerine, minoxidil and others. These drugs must have some chemicophysical trait to be adsorbed by the skin. The concepts of microangiotettonic, microangiopathy, microangiokinesis are very important in erectile dysfunctions. For the future there are perspectives to use microvasculokinesic and antiperossidasic complex, alone or in association with intravenous pharmacotherapy.

Topics: Administration, Cutaneous; Erectile Dysfunction; Humans; Male; Minoxidil; Papaverine; Phentolamine; Vasoactive Intestinal Peptide; Vasodilator Agents; Yohimbine

The present report relates to pharmaceutical composition for the treatment of male impotence. The transdermal application of a potent derivative of vasoactive intestinal peptide (VIP) coupled to a suitable hydrophobic moiety (e.g. stearyl-VIP) in a suitable ointment composition (e.g. Sefsol) enhances sexual activity and erection formation in a variety of impotence models in rats (sterile rats, diabetic rats, and animals with high blood pressure). Furthermore, exchange of the methionine in position 17 with norleucine enhances biological activity. Thus, stearyl-Nle17-VIP may be considered useful for the treatment of impotence.

Topics: Administration, Cutaneous; Animals; Diabetes Mellitus, Experimental; Disease Models, Animal; Erectile Dysfunction; Hypertension; Kinetics; Male; Ointments; Orchiectomy; Penile Erection; Penis; Rats; Reflex; Skin; Tissue Distribution; Vasoactive Intestinal Peptide

In 1982 Virag presented the initial experience of use in diagnosis and treatment of impotence. PGE1 has been showed a safe and effectiveness drug. From september 1989 to october 1991 210 patients with erectile disorders were managed by I.C.I. with PGE1 with minimal side effects.

Topics: Alprostadil; Erectile Dysfunction; Humans; Injections; Ketanserin; Male; Papaverine; Penis; Phentolamine; Vasoactive Intestinal Peptide; Yohimbine

Vasoactive intestinal peptide (VIP), a key penile neurotransmitter, induces erection after local injection in man. To augment the therapeutic potential of VIP for impotence treatment and circumvent difficulties of direct penile injections, a strategy was designed to increase peptide hydrophobicity. This was accomplished by the synthesis of a conjugate of VIP and stearic acid (stearyl-VIP). Upon penile topical application, stearyl-VIP, in contrast to native VIP, significantly increased sexual function as measured by copulatory activity and penile reflexes (erections) in testosterone-treated, castrated rats. In addition, stearyl-VIP penetrated the body in amounts severalfold greater than VIP. Pharmacokinetic studies demonstrated 10-fold higher penile concentrations of stearyl-VIP, as compared with that measured in the blood 15 min after application, with a gradual decrease thereafter. The peak of incorporation into peripheral tissues that was observed 30 min after administration was 1,000-fold less than that found in the penile tissue. Tissue extraction and chromatographic analysis revealed that stearyl-VIP remained essentially intact for greater than or equal to 15 min and was cleared after 1 h. Thus, topically administered stearyl-VIP had increased bioavailability in comparison with VIP without apparent toxicity, suggesting significant therapeutic potential.

Topics: Animals; Disease Models, Animal; Erectile Dysfunction; Male; Penile Erection; Rats; Sexual Behavior, Animal; Stearic Acids; Vasoactive Intestinal Peptide

A total of 52 men, median age 55 years (range 28 to 74 years), with erectile failure was treated with vasoactive intestinal polypeptide and phentolamine. Impotence was classified as psychogenic in 3 patients, psychogenic/arteriogenic in 3, arteriogenic in 25, arteriogenic/neurogenic in 4, neurogenic in 5, venous leakage/psychogenic in 2, venous leakage/neurogenic in 1 and following venous leak surgery in 9. The patients were treated with 30 micrograms vasoactive intestinal polypeptide and 0.5 to 2.0 mg. phentolamine. A total of 1,380 self-injections was given and the number of injections per patient varied from 5 to 245. No patient had priapism, corporeal fibrosis or other serious complications. After sexual stimulation all patients obtained erection sufficient for penetration. Following ejaculation rigidity decreased normally. The median duration of treatment was 6 months (range 1 to 22). Nine patients discontinued treatment. One patient with severe arteriosclerosis experienced decreased effectiveness of the drug and received a penile prosthesis. Five patients elected not to perform self-injection any longer, 1 psychogenic impotent patient was cured, and 1 patient discontinued therapy due to palpitation and sweating. One patient died of a myocardial infarction not associated with this therapy.

Topics: Adult; Aged; Drug Administration Schedule; Drug Therapy, Combination; Erectile Dysfunction; Humans; Injections; Male; Middle Aged; Phentolamine; Self Administration; Vasoactive Intestinal Peptide

The deep dorsal penile vein was obtained from seven patients undergoing surgery for erectile dysfunction. The veins were studied histologically and immunohistochemically for serotonin, dopamine beta-hydroxylase, vasoactive intestinal polypeptide, neuropeptide Y, substance P, calcitonin gene-related peptide, somatostatin, and [Leu]- and [Met]enkephalin. Histologically, the deep dorsal vein was found to be a large muscular vein with a thin endothelial lining. The tunica media was composed of an inner longitudinally and an outer circularly arranged smooth muscle layer. Numerous vasa vasorum (up to 30 in a single transverse section) were found in the tunica adventitia. The greatest density of nerves supplying the deep dorsal vein and vasa vasorum were neuropeptide Y-immunoreactive nerves followed (in a decreasing order) by vasoactive intestinal polypeptide- and dopamine beta-hydroxylase-immunoreactive nerves. Substance P-, calcitonin gene-related peptide- and somatostatin-immunoreactive nerves, but not serotonin-, [Leu]- and [Met]enkephalin-immunoreactive nerves, were occasionally found around the deep dorsal vein. All these nerve fibers were confined to the adventitial-medial border except neuropeptide Y-immunoreactive nerves which in addition penetrated the tunica media to the subendothelial layer of the deep dorsal vein. In contrast, neuropeptide Y-immunoreactive nerves supplying the vasa vasorum were always confined to the adventitial-medial border. The possible function of the medial innervation of the deep dorsal vein by neuropeptide Y-immunoreactive nerves is discussed.

Topics: Adult; Dopamine beta-Hydroxylase; Erectile Dysfunction; Humans; Immunohistochemistry; Male; Middle Aged; Neuropeptide Y; Neuropeptides; Penile Erection; Penis; Serotonin; Vasoactive Intestinal Peptide; Veins

It has been suggested that vasoactive intestinal polypeptide (VIP) may be involved in the nervous control of penile tumescence and erection. VIP ergic nerves are present in the human penis, especially around the prudendal arteries and the corpus cavernosum. However, we have shown that VIP is unlikely to be non-adrenergic, non-cholinergic inhibitory transmitter for penile erection. The aim of this presentation is also to analyse other neurotransmitters of penile erection. This included discussion on: 1. motor neurotransmission; 2. non-adrenergic, non-cholinergic inhibitory transmission; 3. endogenously formed relaxants in the corpus cavernosum; 4. involvement of endothelium-derived relaxing factor(s) and; 5. role of prostanoids in penile erection and others.

Topics: Alprostadil; Erectile Dysfunction; Humans; Male; Neurotransmitter Agents; Papaverine; Penile Erection; Priapism; Receptors, Adrenergic, alpha; Trazodone; Vasoactive Intestinal Peptide; Yohimbine

Penile erection is controlled by a valvular structure in the helicine artery in humans. The opening and closing of this valve are believed to be regulated by the autonomic nervous system, especially through the release of vasoactive intestinal polypeptide (VIP). We determined the content of VIP in cavernous tissue in 18 impotent patients and in 5 normal controls by radioimmunoassay, and we examined the distribution of VIP-ergic nerve fibers in cavernous tissue by an immunohistochemical method. As a result, it was found that the lower penile VIP content was more frequent among patients with organic impotence than among the controls. Furthermore, VIP-ergic nerve fibers were seen to be diffusely and loosely distributed in a large number of organic impotence patients. These findings suggest that organic impotence in some patients may be due to decreases in the VIP content and in VIP-ergic nerve fibers.

Topics: Adolescent; Adult; Aged; Erectile Dysfunction; Humans; Male; Middle Aged; Nerve Fibers; Penis; Vasoactive Intestinal Peptide

The article discusses drugs which promote erection when injected via the intracavernous (IC) route during consultation. The diagnostic and therapeutic applications in the treatment of impotence are discussed also. 25% of impotent patients noted an improvement after this treatment while 50% of patients suffering from impotence of psychological origin noted an improvement. Auto-injection is also discussed. IC treatment now seems justified in most cases which have not responded to traditional therapeutic approaches and this includes cases of psychological origin. Vasoactive drugs can be described as being inducers (use of these drugs induces a rigid erection, even in the presence of the doctor), facilitating drugs (which produce a rigid erection only if sexual stimulation is present also) and inhibitors (which stop the erection). The former group (which has papaverine as leader) produces a significant number of side effects, not least of these being priapism; there is a risk of lasting iatrogenic impotence which is not negligible. These risks are reduced considerably when one uses facilitating drugs which, although less powerful, suffice in treating a large proportion of cases of impotence. Papaverine can not be replaced as a diagnostic drug but facilitating drugs should be used first in therapy and inducers should be used only if these facilitating drugs have failed.

Topics: Adrenergic alpha-Antagonists; Erectile Dysfunction; Humans; Injections; Male; Papaverine; Phenoxybenzamine; Priapism; Prostaglandins E; Vasoactive Intestinal Peptide

Intracavernosally injected vasoactive intestinal polypeptide (VIP) (2 micrograms and 4 micrograms) resulted in penile tumescence even in men with predominantly organic impotence. Papaverine and phentolamine were successful in inducing erections in all subjects studied but the addition of VIP to this combination improved the erectile response further. A combination of papaverine and VIP produced penile rigidity similar to that with papaverine and phentolamine. While intracavernosal VIP alone produced disappointing penile responses, its combination with papaverine potentiated the response to this drug, probably by increasing venous outflow resistance.

Topics: Adult; Aged; Drug Therapy, Combination; Erectile Dysfunction; Humans; Male; Middle Aged; Papaverine; Penile Erection; Phentolamine; Vasoactive Intestinal Peptide

Penile tissue (consisting of corpus cavernosum and tunica albuginea) was obtained from 19 patients undergoing surgery for the implantation of penile prostheses. The tissue was examined for vasoactive intestinal polypeptide-like immunoreactivity in nerves, acetylcholinesterase-positive staining in nerves and noradrenaline content. Impotence was due to a variety of causes; 11 patients were classified as a 'non-neuropathic' group on the basis of their clinical history which included Peyronie's disease, vascular disease, hypertension and psychogenic impotence. Vasoactive intestinal polypeptide-like immunoreactive and acetylcholinesterase-positive nerves were present and the pattern and distribution were similar in each patient in this group. The noradrenaline content of the tunica albuginea was significantly lower than the corpus cavernosum (p less than 0.02), although there was a linear relationship between the noradrenaline contents of the two regions (r = 0.95, p less than 0.01). By comparison, a complete absence of vasoactive intestinal polypeptide-like immunoreactivity in nerves was observed in a patient with a cauda equina lesion. Five out of six diabetic patients studied revealed a marked reduction in vasoactive intestinal polypeptide-like immunoreactivity in nerves associated with the cavernous smooth muscle, while acetylcholinesterase-positive staining was reduced in three out of five diabetic patients studied. The noradrenaline content of the corpus cavernosum from diabetic patients was significantly lower (p less than 0.02) than that of the 'non-neuropathic' group. The noradrenaline content of the tunica albuginea, however, was similar in both groups. The results provide evidence that VIPergic, cholinergic and adrenergic nerves in the penis are affected in diabetes mellitus and thus may contribute to the development of impotence in diabetic patients.

Topics: Acetylcholinesterase; Aged; Diabetes Complications; Diabetic Neuropathies; Erectile Dysfunction; Humans; Male; Middle Aged; Norepinephrine; Parasympathetic Nervous System; Penis; Staining and Labeling; Sympathetic Nervous System; Vasoactive Intestinal Peptide

Intracavernosal and peripheral venous vasoactive intestinal polypeptide (VIP) levels were measured in men with predominantly organic or predominantly psychogenic impotence. The measurements were taken at intervals up to 30 min following intracavernosal injections of saline, papaverine hydrochloride and papaverine hydrochloride and phentolamine. Levels were also measured after tactile and visual sexual stimulation and following an intravenous injection of papaverine and phentolamine. A penile erection occurred in all men receiving intracavernosal vasoactive compounds. The mean VIP concentration did not alter significantly in either cavernosal or peripheral venous blood during the erection. Mean VIP concentrations were significantly greater in the neurogenic (all diabetic) group than in the other groups studied. Mean cavernosal and peripheral VIP concentrations did not alter following tactile or visual sexual stimulation and no significant alteration in mean peripheral venous VIP concentration occurred following injection of papaverine and phentolamine. The putative role of VIP in the induction of penile erection has not been elucidated in these studies.

Topics: Erectile Dysfunction; Humans; Male; Papaverine; Penile Erection; Phentolamine; Vasoactive Intestinal Peptide

Vasoactive intestinal polypeptide (VIP)-containing nerves were depleted in the penises of 28 impotent men. The extent of the decrease in VIP-containing nerves broadly reflected the severity of erectile dysfunction. VIP-immunoreactive nerves were most depleted in those men with complete erectile impotence, irrespective of the aetiology of the dysfunction, whereas in those men in whom some erectile function persisted, loss of VIP-immunoreactive nerves was more variable and less complete. Conventional histology demonstrated only mild changes (muscle atrophy and occasional thickening of blood vessel walls). VIP levels, measured by radioimmunoassay of tissue extracts, were depleted by more than 80% in penises from impotent diabetics (43.4 +/- 9.9 pmol/g wet weight [mean +/- SEM]), when compared with 6 controls (189.9 +/- 45.9 pmol/g). These findings not only support the contention that VIP may be the principal neurotransmitter involved in penile erection, but also suggest that depletion of this powerful vasodilatory peptide may play a key role in the development of penile impotence.

Topics: Adult; Aged; Erectile Dysfunction; Humans; Male; Middle Aged; Nerve Fibers; Penis; Radioimmunoassay; Vasoactive Intestinal Peptide

Vasoactive intestinal polypeptide (VIP) has been demonstrated by immunofluorescence histochemistry in nerves in human and rat penile tissue. A reduction in VIP-like immunoreactivity in nerves was revealed in tissue from streptozotocin-diabetic rats and a human diabetic with impotence. These results suggest that an impairment in the VIP-ergic innervation in penile tissue may be an important factor in the development of impotence in diabetes. They also support the view that the streptozotocin-treated rat is a useful experimental model for diabetic autonomic neuropathy.

Topics: Animals; Diabetes Complications; Diabetes Mellitus; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Erectile Dysfunction; Fluorescent Antibody Technique; Humans; Male; Penis; Rats; Vasoactive Intestinal Peptide

Topics: Adult; Erectile Dysfunction; Gastrointestinal Hormones; Humans; Male; Middle Aged; Muscle, Smooth; Neurotransmitter Agents; Penis; Vasoactive Intestinal Peptide