-
Neurotoxicity Research Dec 2022Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by loss of neurons and synapses. The aim of this study was to investigate the effect of...
Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by loss of neurons and synapses. The aim of this study was to investigate the effect of somatostatin analogue Vapreotide in an in vitro Alzheimer's model and its effects based on the relationship between somatostatinergic transmission and neurodegenerative functions. In this study, tau transfection was performed using the MAPT gene cloned into the pcDNA3.1 vector and transfection reagent into the SH-SY5Y cell line. In viability experiments using 10 µM Memantine as a positive control, it was observed that Vapreotide at 50 µM (p < 0.0001) and 100 µM (p < 0.05) had a protective effect on cell viability, 100 µM CYN154806 was found to decrease (p < 0.05) cell viability. It was determined that Vapreotide, decreased the expression levels (50 µM-p < 0.001; 100 µM-p < 0.001; 200 µM-p < 0.0001) and phosphorylation of Tau and p-Tau proteins by western blots. With the qRT-PCR method, it was found that Vapreotide, decreased the BAX/BCL2 (50 µM-p < 0.001; 100 µM-p < 0.01; 200 µM-p < 0.001) expression level and decreased the expression level (50 µM-p < 0.01; 100 µM-p < 0.01; 200 µM-p < 0.001) of the APOE4 gene, which constitutes a genetic risk for AD. This study demonstrates a potential therapeutic role for a somatostatin analogue Vapreotide in Alzheimer's disease.
Topics: Humans; Alzheimer Disease; Neuroprotective Agents; Amyloid beta-Peptides; Neurodegenerative Diseases; Cell Line, Tumor; Neuroblastoma; tau Proteins; Somatostatin; Transfection; Phosphorylation
PubMed: 36378411
DOI: 10.1007/s12640-022-00588-2 -
Expert Opinion on Pharmacotherapy Oct 2009Portal hypertension is a clinically important consequence of cirrhosis that can lead to morbidities such as variceal bleeding, hepatic encephalopathy and ascites. All of... (Review)
Review
BACKGROUND
Portal hypertension is a clinically important consequence of cirrhosis that can lead to morbidities such as variceal bleeding, hepatic encephalopathy and ascites. All of these outcomes carry high mortality rates. There have been several drugs created to assist with endoscopic therapy for the treatment of acute variceal bleeding. Recently, vapreotide has been studied in patients to evaluate its efficacy as treatment for acute variceal hemorrhage. Although no comparisons have been made between vapreotide and other somatostatin analogues, this drug has been shown to have efficacy in the control of acute variceal bleeding as well as reducing the risk of recurrent bleeding and death, especially when started prior to endoscopy.
OBJECTIVE
This paper reviews the literature regarding the basic science and clinical efficacy of vapreotide in acute variceal bleeding.
METHODS
We used a PubMed/Medline search in order to review the literature regarding the drug, vapreotide.
RESULTS/CONCLUSIONS
Vapreotide appears to have benefit in the control of acute variceal bleeding. It is easy to administer and has few side effects, which are minor. These findings endorse the need for future trials to evaluate vapreotide and its use in acute variceal hemorrhage, a morbidity among patients with cirrhosis.
Topics: Esophageal and Gastric Varices; Female; Gastrointestinal Hemorrhage; Humans; Hypertension, Portal; Liver Cirrhosis; Somatostatin; Treatment Outcome; Vasoconstrictor Agents
PubMed: 19708854
DOI: 10.1517/14656560903207019 -
Expert Review of Gastroenterology &... Apr 2008Variceal bleeding is a life-threatening complication of portal hypertension. The recommended treatment includes the early administration of a vasoactive drug. Vapreotide... (Review)
Review
Variceal bleeding is a life-threatening complication of portal hypertension. The recommended treatment includes the early administration of a vasoactive drug. Vapreotide is a somatostatin analogue with a different receptor affinity to octreotide. It decreases portal pressure and blood flow of collateral circulation in rats with cirrhosis. The pivotal study of early administration of vapreotide in patients with cirrhosis and variceal bleeding has shown a significant improvement in bleeding control and, in the subset of patients with significant bleeding, a significant reduction in mortality. In addition, a meta-analysis of four randomized studies has shown a significant improvement in bleeding control. Vapreotide administrated via the intravenous route is simple to use, with practically no contraindications and few, usually minor, side effects.
Topics: Antineoplastic Agents; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Humans; Somatostatin
PubMed: 19072353
DOI: 10.1586/17474124.2.2.185 -
IDrugs : the Investigational Drugs... Nov 2000Debiopharm, under license from Tulane University, is developing vapreotide, a somatostatin analog, for the potential treatment of cancer, GI disorders and bleeding....
Debiopharm, under license from Tulane University, is developing vapreotide, a somatostatin analog, for the potential treatment of cancer, GI disorders and bleeding. Phase III trials have been initiated in France, investigating the utility of vapreotide in the treatment of prostate cancer. Phase III trials are also underway in France and Asia in patients with acute bleeding from esophageal varices. Debiopharm is also investigating the use of vapreotide in the treatment of acromegaly, gastrointestinal fistulae, AIDS-related and chemotherapy-induced diarrhea, and various neuroendocrine tumors. Vapreotide may also be useful for inducing hemostasis in cases of acute hemorrhage of the upper gastrointestinal tract.
PubMed: 16047258
DOI: No ID Found -
Nanotechnology Feb 2019A new type of vapreotide-templated Ag/Au bimetallic nanoshells (Vap@Ag/AuNSs) were successfully designed and fabricated based on polypeptide-directed mineralization and...
A new type of vapreotide-templated Ag/Au bimetallic nanoshells (Vap@Ag/AuNSs) were successfully designed and fabricated based on polypeptide-directed mineralization and hierarchical self-assembly mechanisms under mild synthetic conditions. The nanoparticles with polypeptides serving as a core and coated Ag/Au bimetallic nanoshells exhibit diverse advantages, such as excellent biocompatibility, tumor targeting and low-cost. The Vap@Ag/AuNSs share excellent dispersibility, uniform size (120 nm) and a positive zeta potential (36.74 ± 4.49 mV), hence they easily accumulate in negatively charged tumor tissue. The results of thermal imaging, temperature variation assays and photothermal conversion efficiency (41.6%) indicated that Vap@Ag/AuNSs have excellent photothermal conversion capability. Based on their photothermal response, as well as biocompatibility determined by MTT assay, the prominent anti-tumor effects of Vap@Ag/AuNSs have been verified by fluorescein diacetate staining. Therefore, Vap@Ag/AuNSs are novel and promising candidates for photothermal tumor therapy.
Topics: Antineoplastic Agents; Biocompatible Materials; Gold; Minerals; Nanoshells; Silver; Somatostatin; Temperature
PubMed: 30520422
DOI: 10.1088/1361-6528/aaf0db -
Drugs in R&D 2003Vapreotide [Octastatin, Sanvar, RC 160, BMY 41606] is a somatostatin analogue developed at Tulane University School of Medicine, New Orleans, USA, which holds patent... (Review)
Review
Vapreotide [Octastatin, Sanvar, RC 160, BMY 41606] is a somatostatin analogue developed at Tulane University School of Medicine, New Orleans, USA, which holds patent rights for vapreotide. Vapreotide provides a much higher metabolic stability than its parent compound. Vapreotide was licensed to Debiopharm for development in Europe. Vapreotide is usually administered SC although a slow-release IM formulation is also available. Other sustained-release formulations are under development. H3 Pharma plans to sign agreements for all indications in the core markets of North America, Europe and in non-core geographic regions during 2003. H3 Pharma will also seek to obtain registration and early market entry in non-core countries with help from partners. Sanvar Immediate Release (IR) has been submitted for approval within the European Union for the treatment of acute oesophageal variceal bleeding (EVB). Sanvar IR has been awarded orphan drug status in the US for EVB. In July 2003, H3 Pharma received written confirmation from the US FDA that the dossier for Sanvar is fileable for registration in the United States for the treatment of esophageal variceal bleeding (EVB). The Sanvar IR (immediate-release) formulation is expected to enter the US market by late 2004. H3 Pharma expects to file for Latin American registration for this indication in the second half of 2003, with registrations in other regions to follow. Sanvar SR has been submitted for Orphan Drug designation.
Topics: Animals; Antineoplastic Agents; Clinical Trials, Phase II as Topic; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Humans; Injections, Subcutaneous; Neoplasms; Somatostatin
PubMed: 12952505
DOI: 10.2165/00126839-200304050-00010 -
Journal of Hepatology Jul 2002
PubMed: 12076882
DOI: 10.1016/s0168-8278(02)00170-8 -
Neuroimmunomodulation 2013Vapreotide, a synthetic analog of somatostatin, has analgesic activity most likely mediated through the blockade of neurokinin-1 receptor (NK1R), the substance P...
OBJECTIVES
Vapreotide, a synthetic analog of somatostatin, has analgesic activity most likely mediated through the blockade of neurokinin-1 receptor (NK1R), the substance P (SP)-preferring receptor. The ability of vapreotide to interfere with other biological effects of SP has yet to be investigated.
METHODS
We studied the ability of vapreotide to antagonize NK1R in three different cell types: immortalized U373MG human astrocytoma cells, human monocyte-derived macrophages (MDM) and a human embryonic kidney cell line, HEK293. Both U373MG and MDM express endogenous NK1R while HEK293 cells, which normally do not express NK1R, are stably transformed to express human NK1R (HEK293-NK1R).
RESULTS
Vapreotide attenuates SP-triggered intracellular calcium increases and nuclear factor-κB activation in a dose-dependent manner. Vapreotide also inhibits SP-induced interleukin-8 and monocyte chemotactic protein-1 production in HEK293-NK1R and U373MG cell lines. Vapreotide inhibits HIV-1 infection of human MDM in vitro, an effect that is reversible by SP pretreatment.
CONCLUSIONS
Our findings indicate that vapreotide has NK1R antagonist activity and may have a potential application as a therapeutic intervention in HIV-1 infection.
Topics: Analgesics; Aprepitant; Calcium; Cell Line; Chemokine CCL2; Cytokines; Dose-Response Relationship, Drug; Drug Interactions; Gene Expression Regulation; Humans; Macrophages; Morpholines; NF-kappa B; Neurokinin-1 Receptor Antagonists; Receptors, Neurokinin-1; Receptors, Somatostatin; Signal Transduction; Somatostatin; Substance P; Transfection; gag Gene Products, Human Immunodeficiency Virus
PubMed: 23921645
DOI: 10.1159/000350468 -
The New England Journal of Medicine Jan 2001In patients with cirrhosis, pharmacologic or endoscopic treatment may control variceal bleeding. However, the effects of early administration of a somatostatin analogue... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
BACKGROUND
In patients with cirrhosis, pharmacologic or endoscopic treatment may control variceal bleeding. However, the effects of early administration of a somatostatin analogue followed by endoscopic treatment are unknown.
METHODS
We studied the effects of treatment with vapreotide, a somatostatin analogue, begun before endoscopic treatment in 227 patients with cirrhosis who were hospitalized for acute upper gastrointestinal bleeding. The patients were randomly assigned to receive vapreotide (a 50-microg intravenous bolus followed by an infusion at a rate of 50 microg per hour for five days) or placebo within a mean (+/-SD) of 2.3+/-1.5 hours after admission. All the patients received endoscopic treatment a mean of 2.6+/-3.3 hours after the infusion was begun. After the exclusion of 31 patients whose bleeding was not caused by portal hypertension, there were 98 patients in each group.
RESULTS
At the time of endoscopy, active bleeding was evident in 28 of 91 patients in the vapreotide group (31 percent), as compared with 43 of 93 patients in the placebo group (46 percent) (P=0.03). During the five-day infusion, the primary objective--survival and control of bleeding--was achieved in 65 of 98 patients in the vapreotide group (66 percent) as compared with 49 of 98 patients in the placebo group (50 percent) (P=0.02). The patients in the vapreotide group received significantly fewer blood transfusions (2.0+/-2.2 vs. 2.8+/-2.8 units, P=0.04). Overall mortality rates at 42 days were not significantly different in the two groups.
CONCLUSIONS
In patients with cirrhosis and variceal bleeding, the combination of vapreotide and endoscopic treatment is more effective than endoscopic treatment alone as a method of controlling acute bleeding. However, the use of combination therapy does not affect mortality rates at 42 days.
Topics: Blood Transfusion; Combined Modality Therapy; Endoscopy; Esophageal and Gastric Varices; Female; Gastrointestinal Hemorrhage; Humans; Hypertension, Portal; Liver Cirrhosis; Male; Middle Aged; Multivariate Analysis; Sclerotherapy; Secondary Prevention; Somatostatin
PubMed: 11136956
DOI: 10.1056/NEJM200101043440104 -
British Journal of Clinical Pharmacology Feb 1999Somatostatin analogues (e.g. vapreotide) are used for treatment of acromegaly, endocrine tumours and variceal bleeding. The pharmacodynamic effects of vapreotide have,... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
The effects of vapreotide, a somatostatin analogue, on gastric acidity, gallbladder emptying and hormone release after 1 week of continuous subcutaneous infusion in normal subjects.
AIMS
Somatostatin analogues (e.g. vapreotide) are used for treatment of acromegaly, endocrine tumours and variceal bleeding. The pharmacodynamic effects of vapreotide have, however, not been documented in the gastrointestinal tract. The aim of this study was to investigate the effects of continuous vapreotide administration on gastric acidity, gallbladder contraction and hormone release.
METHODS
Ten healthy males participated in this randomised, placebo-controlled, double-blind, crossover trial. A constant vapreotide (or placebo) infusion (1.5 mg day(-1) s.c.) was given for 7 days with a portable pump. Intragastric pH was monitored on days 2 and 7. Gallbladder volume was sonographically assessed and the maximal ejection fraction was calculated. In addition basal and postprandial plasma levels of gastrin and cholecystokinin (CCK) were measured.
RESULTS
After an initial increase in the median 24 h intragastric pH to a value of 2.6 on day 2, vapreotide's effect on pH decreased: (day 7: median pH=1.9; respective placebo values were 1.7 and 1.5). On the same days with vapreotide treatment, gallbladder contraction and plasma levels of CCK were reduced; maximal ejection fractions after meal stimulation were 18% and 20% (respective placebo values were 57% and 62%). Plasma gastrin levels were not changed with vapreotide treatment.
CONCLUSIONS
The short lasting effect of vapreotide on intragastric acidity suggests a down-regulation of somatostatin receptors during treatment. The lack of effect on gastrin indicates that the effects on gastric pH are not mediated by gastrin. Constant vapreotide infusion (but not placebo) reduced gallbladder contraction suggesting a long-lasting effect on biliary function.
Topics: Administration, Cutaneous; Adult; Antineoplastic Agents; Cholecystokinin; Cross-Over Studies; Double-Blind Method; Drug Administration Schedule; Gallbladder Emptying; Gastric Acid; Gastrins; Humans; Hydrogen-Ion Concentration; Infusion Pumps; Male; Placebos; Somatostatin; Time Factors
PubMed: 10190655
DOI: 10.1046/j.1365-2125.1999.00878.x