RPEP-00078 · 1988A commercially purchased synthetic dynorphin A-(1-13) raised cytosolic calcium in rat pituitary cells. However, this effect was NOT caused by dynorphin itself.
When the same preparation was purified by HPLC, the calcium-raising effect disappeared. HPLC combined with LHRH radioimmunoassay revealed contamination with a LHRH-like compound (luteinizing hormone-releasing hormone).
The LHRH antagonist blocked the calcium effect, confirming the contamination. Pure dynorphin A-(1-13), dynorphin A-(2-13), leu-enkephalin, beta-endorphin, morphine, and U50,488H all had zero effect on pituitary calcium.
LHRH itself raised calcium by about 50 nM, which was blocked by the LHRH antagonist.
Knepel, W; Schöfl, C; Wesemeyer, G; Götz, D M · In Vitro
RPEP-00100 · 1988Amniotic fluid thymosin alpha 1 levels were remarkably higher than newborn serum levels and increased in a logarithmic pattern with fetal age (r = 0.838).
Welch, R A; Lee, H H; Sokol, R J; Mutchnick, M G · Cross Sectional
RPEP-00187 · 1991Peptides synthesized by azide coupling contained mutagenic contaminants undetectable by HPLC. Switching synthesis methods or using counter-current purification eliminated the problem.
Castellino, S; de Castiglione, R; Forino, R; Galantino, M; Pulci, R · In Vitro
RPEP-00214 · 1991Chronic low-dose PCB exposure increased serum complement and NK cell activity while altering other immune parameters in rhesus monkeys.
Tryphonas, H; Luster, M I; White, K L; Naylor, P H; Erdos, M R; Burleson, G R; Germolec, D; Hodgen, M; Hayward, S; Arnold, D L · Animal Study
RPEP-00218 · 1992Column purification validation requires qualification of raw materials, equipment, and process, ideally designed in from the start. Combined with quality control, this ensures batch-to-batch consistency.
· Review
RPEP-00267 · 1993Lead exposure alters brain opioid peptide concentrations and receptor binding across multiple brain regions, potentially explaining neurological toxicity symptoms.
Kitchen, I · Review
RPEP-00340 · 1995Eschscholtzia californica and Corydalis cava extracts inhibited peroxidase- and tyrosinase-mediated dimerization and oxidation of enkephalin peptides.
Reimeier, C; Schneider, I; Schneider, W; Schäfer, H L; Elstner, E F · In Vitro
RPEP-00529 · 1999BPC-157 co-administration with chronic diazepam (10 days) prevented tolerance development, maintained anticonvulsant efficacy, and reduced withdrawal seizure severity at both 10 μg/kg and 10 ng/kg doses in rats.
Jelovac, N; Sikiric, P; Rucman, R; Petek, M; Perovic, D; Marovic, A; Anic, T; Seiwerth, S; Mise, S; Pigac, B; Duplancie, B; Turkovic, B; Dodig, G; Prkacin, I; Stancic-Rokotov, D; Zoricic, I; Aralica, G; Sebecic, B; Ziger, T; Slobodnjak, Z · Animal Study
RPEP-00650 · 2001TFA contamination from peptide synthesis inactivated thymosin alpha-1's clonal growth inhibition activity, demonstrating the need for rigorous purification and biological activity testing of therapeutic peptide preparations.
Bianco-Batlles, D; Naylor, C W; Moshier, J A; Dosescu, J; Naylor, P H · In Vitro
RPEP-03748 · 2018While most manufactured bioactive peptides show negligible toxicity, some naturally occurring peptides and enzymes can induce significant toxicity. The review identifies six main safety concerns with biologically active peptides: intestinal wall disruption, erythrocyte and lymphocyte toxicity, free radical production, enzyme-mediated tissue damage, immune-mediated tissue damage, and direct cytotoxicity.
The authors advocate for systematic safety evaluation — particularly using in silico (computational) methods — before peptides are used in food production or pharmaceutical applications. They emphasize that both immunogenicity (immune reactions against the peptide itself) and direct toxicity need assessment, as the growing use of peptides across food, cosmetics, and medicine demands standardized safety protocols.
Khan, Fazlullah; Niaz, Kamal; Abdollahi, Mohammad · Review
RPEP-05013 · 2020Amylin and pramlintide increased amyloid-beta production by modulating APP and γ-secretase in lipid rafts, leading to increased Aβ burden, synaptic loss, and neuroinflammation in TgSwDI Alzheimer's mice.
Mousa, Youssef M; Abdallah, Ihab M; Hwang, Misako; Martin, Douglas R; Kaddoumi, Amal · Animal
RPEP-05100 · 2020Neither DPP-4 inhibitors (HR 1.07, 95% CI 0.87-1.32) nor GLP-1 receptor agonists (HR 1.02, 95% CI 0.68-1.54) were associated with increased lung cancer risk, with no duration-response relationship.
Rouette, J; Yin, H; Yu, O H Y; Bouganim, N; Platt, R W; Azoulay, L · Cohort
RPEP-05292 · 20215.3% of migraine patients with Raynaud phenomenon experienced microvascular complications from CGRP antagonists, including rare but serious events like gangrene requiring digit amputation.
Breen, Ilana D; Brumfiel, Caitlin M; Patel, Meera H; Butterfield, Richard J; VanderPluym, Juliana H; Griffing, Leroy; Pittelkow, Mark R; Mangold, Aaron R · Observational
RPEP-05303 · 2021Across 200,148 participants and 396,457 person-years, GLP-1 RAs showed cardiovascular safety with potential MACE benefit for liraglutide (PE range 0.53-0.95) and no association with pancreatitis, pancreatic cancer, breast cancer, or hypoglycemia.
Caparrotta, Thomas M; Templeton, Jack B; Clay, Thomas A; Wild, Sarah H; Reynolds, Rebecca M; Webb, David J; Colhoun, Helen M · Systematic Review
RPEP-05323 · 2021ADA prevalence ranged from <1% to ~18% and neutralizing ADA from 0-12% across CGRP mAbs, with adverse events related to ADA formation rare across all four approved migraine antibodies.
Cohen, Joshua M; Ning, Xiaoping; Kessler, Yoel; Rasamoelisolo, Michele; Campos, Verena Ramirez; Seminerio, Michael J; Krasenbaum, Lynda J; Shen, Honglue; Stratton, Jennifer · Review
RPEP-05353 · 2021Selank and phenibut are poorly studied GABAergic drugs sold as US dietary supplements. Phenibut poison control calls have increased substantially, and both carry risks of dependence, withdrawal, and serious adverse effects when misused.
Doyno, Cassandra R; White, C Michael · Review
RPEP-05413 · 2021Anti-CGRP monoclonal antibodies represent a paradigm shift in migraine prevention as the first treatments designed specifically for migraine. All four (erenumab, fremanezumab, galcanezumab, eptinezumab) have demonstrated efficacy in clinical trials.
González-Hernández, Abimael; Marichal-Cancino, Bruno A; Villalón, Carlos M · Review
RPEP-05461 · 2021GLP-1 receptor agonists were proposed to cause hypoglycemia in healthy normoglycemic subjects, challenging the assumption of purely glucose-dependent action. The FDA evaluated all 12 marketed GLP-1 RAs for potential hypoglycemia safety signals. Risk appears dependent on individual factors.
Ja'arah, Daria; Al Zoubi, Mazhar Salim; Abdelhady, Gamal; Rabi, Firas; Tambuwala, Murtaza M · Review
RPEP-05473 · 2021A cell-based MRGPRX2 assay reliably identified peptide compounds causing injection site histamine release and edema in ex vivo skin samples, serving as a replacement for postmortem animal evaluation.
John, Linu M; Dalsgaard, Charlotte M; Jeppesen, Claus B; Conde-Frieboes, Kilian W; Baumann, Katrine; Knudsen, Niels P H; Skov, Per S; Wulff, Birgitte S · Drug Development/Validation Study
RPEP-05476 · 2021Comparison of human liver S9, hepatocyte spheroids, and other in vitro systems revealed model-dependent differences in peptide metabolism prediction, informing best practices for peptide drug development.
Jyrkäs, Juha; Tolonen, Ari · In Vitro Comparative Study
RPEP-09088 · 2024Meta-analyses of long-term randomized controlled trials show DPP-4 inhibitors carry a small increased risk of acute pancreatitis, but GLP-1 receptor agonists and GLP-1/GIP co-agonists do not. GLP-1 receptor agonists and co-agonists are associated with higher rates of cholecystitis and cholelithiasis (gallbladder inflammation and gallstones). No incretin-based drug class is associated with increased pancreatic cancer risk.
Pratley, Richard; Saeed, Zeb I; Casu, Anna · Review
RPEP-09114 · 2024Chemical hypoxia (using DNP) increased paracellular permeability in human colon by 52% (p = 0.003). Both somatostatin (2 μM) and octreotide (0.2 μM) prevented this increase whether given before or after the hypoxic insult.
In rat colon, hypoxia increased total epithelial conductance by 18% (p = 0.016) and macromolecule permeability (FITC-dextran movement) by 43% (p = 0.01). Octreotide pretreatment at 0.2 μM completely prevented both changes.
The mechanism involves IK channels (intermediate conductance potassium channels, KCa3.1/KCNN4) on the basolateral side of the epithelium. Hypoxia activates these channels, opening the paracellular pathway. Somatostatin and octreotide inhibit IK channels, keeping the gut barrier intact.
Rajput, Ibrahim; Rajendran, Vazhaikkurichi M; Nickerson, Andrew J; Lodge, J Peter A; Sandle, Geoffrey I · Ex Vivo
RPEP-09146 · 2024Long-term COX-2 suppression caused diastolic dysfunction and features of HFpEF in aged female mice, while younger mice were unaffected.
Ricciotti, Emanuela; Haines, Philip G; Beerens, Manu; Kartoun, Uri; Castro, Cecilia; Tang, Soon Yew; Ghosh, Soumita; Das, Ujjalkumar S; Lahens, Nicholas F; Wang, Tao; Griffin, Jules L; Shaw, Stanley Y; MacRae, Calum A; FitzGerald, Garret A · Animal Study
RPEP-09151 · 2024Semaglutide does not increase cardiovascular adverse events or mortality but is associated with higher rates of gastrointestinal side effects compared to placebo.
Rivera, Frederick Berro; Arias-Aguirre, Eloise; Aguirre, Zedrick; Ybañez, Mc John C; Rubia, Janos Marc M; Galang, Danica Janine; Lumbang, Grace Nooriza; Ruyeras, Jade Monica Marie J; Magalong, John Vincent; Pine, Polyn Luz; Amigo, John Andrew C; Ansay, Marie Francesca M; Zelenkov, Nenad; Thomas, Steve Samuel; Vijayaraghavan, Krishnaswami · Meta Analysis
RPEP-09154 · 2024GLP-1 receptor agonist use was not associated with increased risk of aspiration or retained gastric contents during outpatient upper endoscopy.
Robalino Gonzaga, Ernesto; Farooq, Aimen; Mohammed, Abdul; Chandan, Saurabh; Fawwaz, Baha; Singh, Gurdeep; Malik, Amna; Zhang, Yiyang; Kadkhodayan, Kambiz · Cohort
RPEP-09158 · 2024Certain synthesis-derived impurities of salmon calcitonin showed potential to bind HLA molecules and stimulate T cells, indicating immunogenicity risk that warrants monitoring.
Roberts, Brian J; Mattei, Aimee E; Howard, Kristina E; Weaver, James L; Liu, Hao; Lelias, Sandra; Martin, William D; Verthelyi, Daniela; Pang, Eric; Edwards, Katie J; De Groot, Anne S · In Vitro
RPEP-09176 · 2024A patient developed rheumatoid arthritis three months after starting CGRP antibody therapy for migraines, suggesting potential autoimmune triggering as an adverse effect.
Rua, Catarina; Beirão, Tiago; Silva, Catarina; Meirinhos, Tiago; Pinto, Patricia; Vieira, Romana; Aleixo-Santos, Joana; Costa, Flávio; Fonseca, Diogo; Pinto, Ana Sofia; Samões, Beatriz; Videira, Taciana · Case Series
RPEP-09181 · 2024Disproportionality analysis of the European Pharmacovigilance database found no elevated signal for suicidal events with GLP-1 receptor agonists as a class.
Ruggiero, Rosanna; Mascolo, Annamaria; Spezzaferri, Angela; Carpentieri, Claudia; Torella, Daniele; Sportiello, Liberata; Rossi, Francesco; Paolisso, Giuseppe; Capuano, Annalisa · Cohort
RPEP-09193 · 2024Reported cutaneous reactions to GLP-1 agonists include dermal hypersensitivity reactions, eosinophilic panniculitis, bullous pemphigoid, and morbilliform drug eruptions. These are rare but clinically significant. Diagnosis requires clinical suspicion, thorough medication history, and supporting histopathology when available. Management centers on stopping the GLP-1 drug and tailoring anti-inflammatory or immunomodulatory treatment to the specific reaction type.
Salazar, Carlos E; Patil, Mihir K; Aihie, Osaigbokan; Cruz, Nicolas; Nambudiri, Vinod E · Review
RPEP-09198 · 2024GLP-1RA use was not associated with higher odds of adverse events compared to FDA-approved non-GLP-1 medications (aOR 1.1, 95% CI 0.5–2.6) or off-label medications (aOR 1.1, 95% CI 0.6–2.3). Notably, starting any antiobesity medication 12 or more months after surgery was associated with dramatically lower risk of adverse events compared to earlier initiation (aOR 0.01, 95% CI 0.0–0.01, p < 0.001).
Samuels, Jason M; Niswender, Kevin D; Roumie, Christianne L; Spann, Matthew D; Flynn, C Robb; Ye, Fei; Blankush, Joseph; Irlmeier, Rebecca; Funk, Luke M; Patel, Mayur B · Cohort
RPEP-09203 · 2024Semaglutide users had significantly higher rates of increased residual gastric content (20.3% vs 3.2%, p<0.001). Discontinuation >21 days in patients with digestive symptoms and >14 days in those without symptoms resulted in RGC comparable to non-users (OR 0.77, 95% CI 0.22-2.01).
Santos, Leonardo Barbosa; Mizubuti, Glenio B; da Silva, Leopoldo Muniz; Silveira, Saullo Queiroz; Nersessian, Rafael Souza Fava; Abib, Arthur de Campos Vieira; Bellicieri, Fernando Nardy; Lima, Helidea de Oliveira; Ho, Anthony M-H; Dos Anjos, Gabriel Silva; de Moura, Diogo Turiani Hourneaux; de Moura, Eduardo Guimarães Hourneuax; Vieira, Joaquim Edson · Cohort
RPEP-09224 · 2024Significant disproportionality was detected for semaglutide-associated suicidal ideation (ROR 1.45, 95% CI 1.18-1.77). Signal strengthened in patients co-taking antidepressants (ROR 4.45) or benzodiazepines (ROR 4.07). Remained significant vs comparators: dapagliflozin (ROR 5.56), metformin (ROR 3.86), orlistat (ROR 4.24). No significant signal detected for liraglutide.
Schoretsanitis, Georgios; Weiler, Stefan; Barbui, Corrado; Raschi, Emanuel; Gastaldon, Chiara · Cohort
RPEP-09230 · 2024Semaglutide 2.4 mg vs placebo reduced all-cause death (HR 0.81, CI 0.71-0.93), non-CV death (HR 0.77, CI 0.62-0.95), and infectious death (HR 0.71, CI 0.51-0.98). Among COVID-19 patients, semaglutide reduced COVID deaths (HR 0.66, CI 0.44-0.96) and serious COVID events (232 vs 277, p=0.04). CV death trended lower (HR 0.85, CI 0.71-1.01).
Scirica, Benjamin M; Lincoff, A Michael; Lingvay, Ildiko; Bogdanski, Pawel; Buscemi, Silvio; Colhoun, Helen; Craciun, Anca-Elena; Ezhov, Marat; Hardt-Lindberg, Søren; Kleist Jeppesen, Ole; Matos, Ana Laura S A; Node, Koichi; Schiele, Francois; Toplak, Hermann; van Beek, André; Weeke, Peter E; Wiviott, Stephen D; Deanfield, John; Ryan, Donna · RCT
RPEP-09233 · 2024Severe hypoglycemia rates: glargine 0.8%, glimepiride 1.3%, liraglutide 0.5%, sitagliptin 0.3% (p<0.05). Hypoglycemic symptoms: glargine 54.2%, glimepiride 68.3%, liraglutide 32.4%, sitagliptin 29.1% (p<0.001). Liraglutide and sitagliptin had significantly less hypoglycemia than glimepiride and glargine.
Seaquist, Elizabeth R; Phillips, Lawrence S; Ghosh, Alokananda; Baker, Chelsea; Bergenstal, Richard M; Crandall, Jill P; Goland, Robin S; Gramzinski, Michaela R; Hox, Sophia H; Hsia, Daniel S; Johnson, Mary L; Lachin, John M; Raskin, Philip; Valencia, Willy M; Waltje, Andrea H; Younes, Naji · RCT
RPEP-09249 · 2024N-terminal histidine of liraglutide reacts with formaldehyde impurities in excipients and PLGA degradation products, forming imidazopyrimidine, glycolyl, and lactolyl interaction products.
Sheikh, Azahar R; Vitore, Jyotsna G; Bhalekar, Vijay S; Jain, Sonali; Kukreja, Divya; Giri, Tushar; Sharma, Nitish; Benival, Derajram; Shah, Ravi P · In Vitro
RPEP-09253 · 2024Non-alcoholic Wernicke encephalopathy occurred in a 37-year-old male patient in the setting of semaglutide use, presenting with dysphagia, slurred speech, word-finding difficulty, and restricted extraocular movements.
Sheth, Krishna; Garza, Elizabeth; Saju, Ajith; Nazir, Natasha; Agarwal, Aditya · Case Series
RPEP-09255 · 2024Dulaglutide caused significant elevation of serum CA19-9 and CA242 levels in an asymptomatic patient, which completely normalized within 6 weeks of drug discontinuation.
Shi, Xiaomin · Case Series
RPEP-12919 · 2025A substantial proportion of patients on GLP-1 receptor agonists had high residual gastric contents before anesthesia despite standard fasting, suggesting current preoperative fasting guidelines may be inadequate for this population.
Pai, Sher-Lu; Nimma, Sindhuja R; Beam, W Brian; VanderWielen, Beth A; Kalagara, Hari K; Bettini, Layne M; Yu, Soojie; Sharpe, Emily E; Harbell, Monica W · Prospective Cohort