Review
This narrative review examines intravenous (IV) peptide and amino acid therapies as potential treatments for erectile dysfunction (ED), a condition involving interrelated vasculogenic, hormonal, and neurological mechanisms in which endothelial dysfunction and oxidative stress are central contributors. The authors conducted a PubMed literature search of English-language publications through October 2024, focusing primarily on studies from the past decade. Four compounds were highlighted: PT-141 (bremelanotide), a melanocortin receptor agonist proposed to act via central nervous system pathways; PnPP-19, a spider venom-derived peptide suggested to work through nitric oxide regulation; and the amino acids L-arginine and L-citrulline, both linked to enhanced endothelial function and nitric oxide synthesis. The review notes that these agents operate through mechanisms distinct from phosphodiesterase type 5 (PDE5) inhibitors, potentially offering alternatives or adjuncts for patients unresponsive to standard therapy. The authors conclude that while early evidence is promising, large-scale clinical trials are needed to establish safety profiles, optimal treatment parameters, and potential synergistic effects with existing ED treatments. As a narrative review, it is subject to selection bias and does not pool quantitative data.
Expert opinion on pharmacotherapy · Mar 2025DOI ↗ Review
This review paper provides a broad overview of glucagon-like peptide-1 (GLP-1), an incretin hormone secreted primarily by intestinal L-cells, pancreatic α-cells, and the central nervous system, and its therapeutic relevance in type 2 diabetes mellitus (T2DM). The authors describe how GLP-1 promotes glucose homeostasis by stimulating insulin secretion, slowing gastric emptying, reducing food intake, and supporting β-cell proliferation. The paper surveys existing GLP-1-based pharmacological strategies, including GLP-1 receptor agonists (single, dual, and triple agonists) and dipeptidyl peptidase-4 (DPP-4) inhibitors, noting that both preclinical and clinical evidence supports their role in improving glycemic control. The review then shifts focus to emerging, non-pharmacological-style strategies: enhancing endogenous GLP-1 production through various physiological and molecular stimuli, and promoting intestinal L-cell differentiation as a means to expand the body's own GLP-1-secreting capacity. The authors frame L-cell differentiation as a particularly promising future therapeutic avenue. As a narrative review, the paper synthesizes existing literature rather than generating new primary data, and its conclusions are limited by the scope and quality of the studies it cites.
Diabetology & metabolic syndrome · Feb 2025DOI ↗ Review
This literature and patent review examines BPC 157 (Body Protection Compound 157), a synthetic pentadecapeptide derived from human gastric juice. The authors surveyed preclinical evidence across multiple disease models, including tissue injury, inflammatory bowel disease, and central nervous system disorders, cataloguing the compound's reported pleiotropic (wide-ranging) biological activities and proposed mechanisms of action. The review also assesses available toxicity and safety data, noting that relatively few side effects have been reported in preclinical settings. Regulatory context is highlighted: BPC 157 has not been approved by the FDA or equivalent global authorities, as no sufficient clinical trials in humans have been completed. The compound was temporarily listed by the World Anti-Doping Agency (WADA) in 2022 but is no longer on the banned list. The authors additionally map recent patent applications and granted patents to reflect growing commercial and research interest. A key limitation acknowledged throughout is that virtually all supporting evidence comes from animal and in vitro studies, meaning the translation of these findings to human health outcomes remains unestablished.
Pharmaceuticals (Basel, Switzerland) · Jan 2025DOI ↗ Review
This review paper evaluates pharmacologic treatments for female sexual dysfunction (FSD), with a primary focus on hypoactive sexual desire disorder (HSDD). The authors examine the two FDA-approved medications for FSD — flibanserin (a daily oral serotonin/dopamine modulator) and bremelanotide (an on-demand injectable melanocortin receptor agonist) — alongside investigational therapies such as Lorexys (a bupropion/trazodone combination) and various testosterone-based treatments. The review synthesizes study outcomes and safety profiles for each agent, and offers clinical guidance on patient selection, diagnosis, expectation setting, side effect management, and patient education. The authors note that while FDA-approved options exist, their clinical uptake has been limited by modest effect sizes, side effect burdens, and barriers to access. Investigational therapies show early promise but require further clinical validation. A key limitation of this paper is its nature as a narrative review, meaning it does not pool data systematically and may be subject to selection bias in the studies included. It does not introduce new primary data.
Clinical obstetrics and gynecology · Jan 2025DOI ↗ Review
This review paper examines the role of zonulin — a protein that regulates intestinal tight junctions (TJs) — in the pathogenesis of Chronic Inflammatory Disorders (CIDs). The authors explore how dysregulation of zonulin contributes to increased intestinal permeability ("leaky gut"), which may facilitate the translocation of harmful substances from the gut into the bloodstream, potentially driving or worsening conditions such as Inflammatory Bowel Disease (IBD), celiac disease, and Multiple Sclerosis (MS). The paper synthesizes preclinical and clinical research on larazotide acetate, a zonulin antagonist, highlighting its potential to improve gut barrier integrity and reduce inflammation in CID patients. The authors also discuss zonulin's promise as a biomarker for intestinal permeability. Key limitations acknowledged by the review include the need for further mechanistic clarification of zonulin antagonists and robust clinical trials to establish their efficacy and safety. As a narrative review, this paper does not generate new primary data, and its conclusions are dependent on the quality and consistency of the underlying studies it synthesizes. The authors call for continued research to inform personalized therapeutic strategies for CIDs.
Current medicinal chemistry · Jan 2025DOI ↗ Review
This review paper examines the current state of knowledge and methodology surrounding the skin permeation of GHK-Cu (glycyl-L-histidyl-L-lysine copper tripeptide), a naturally occurring cosmetically active compound (CAC) associated with properties such as reducing fine lines and wrinkles, improving skin elasticity, and tightening skin. The authors highlight a central challenge: GHK-Cu is relatively hydrophilic, which limits its ability to penetrate the lipophilic stratum corneum, the skin's outermost barrier. The paper reviews liposomal encapsulation as a strategy to improve GHK-Cu's skin permeation potential, and surveys existing methods used to study transdermal transport of CACs—both free and liposome-encapsulated. A key finding from the literature analysis is that research specifically examining liposome-mediated transport of GHK-Cu is sparse, representing a notable gap in the field. The authors argue this gap motivates further methodological development to better assess how liposomes affect GHK-Cu trafficking through skin layers. As a review, the paper synthesizes existing literature rather than presenting original experimental data, and it does not include clinical trials or controlled human studies. Its conclusions about efficacy are therefore inferential and limited by the quality and quantity of the underlying studies reviewed.
Molecules (Basel, Switzerland) · Jan 2025DOI ↗ Review
This review article provides a comprehensive overview of approved and emerging hormone-based anti-obesity medications (AOMs), situating them within the broader context of obesity as a complex, chronic, global disease. The authors summarize the current regulatory landscape, noting that the GLP-1 receptor agonists (GLP-1RAs) liraglutide and semaglutide have received FDA and EMA approval for weight management. The review also covers pipeline agents, including oral GLP-1RAs (semaglutide, danuglipron, orforglipron), the amylin receptor agonist cagrilintide (alone and in combination with semaglutide), and dual agonists such as tirzepatide (GIP/GLP-1), survodutide, mazdutide, and pemvidutide (GLP-1R/GCGR). The authors highlight tirzepatide's placebo-subtracted weight reduction of 17.8% in a 72-week RCT and retatrutide's (a GLP-1R/GCGR/GIPR tri-agonist) placebo-subtracted reduction of 22.1% in a 48-week phase-II trial. The review cautions that long-term safety and cardiovascular outcome data for many of these agents remain incomplete. As a narrative review, it does not conduct original research or meta-analysis, and conclusions are limited by the quality and heterogeneity of the underlying primary studies it synthesizes.
Indian journal of endocrinology and metabolism · Sep 2024DOI ↗ Review
This review paper examines the history, development, and scientific utility of key synthetic tool compounds used to study the melanocortin receptor (MCR) family — a group of five Class A G protein-coupled receptors (GPCRs) involved in diverse physiological processes including pigmentation, steroidogenesis, and energy homeostasis. The authors trace how synthetic derivatives of the endogenous agonist α-MSH, including NDP-MSH (melanotan I), melanotan II (MTII), and SHU9119, have become essential pharmacological tools for the field. The review discusses how these compounds are used to validate cell lines stably expressing melanocortin receptors, serve as reference ligands in high-throughput screening, inform structure-activity relationship (SAR) studies, and act as core ligands in cryo-EM structural investigations of active and inactive receptor complexes. The paper also notes that these tool compounds have served as scaffolds for FDA-approved drugs. Limitations of the review include its descriptive, non-experimental nature and its focus on synthesizing existing literature rather than presenting new empirical data. It provides important context for researchers working on MCR pharmacology but does not itself generate clinical or mechanistic evidence.
ACS pharmacology & translational science · Aug 2024DOI ↗ Review
This review article explores phenotypic drug discovery (PDD) as a research framework and uses thymosin alpha-1 (Tα1), a thymic peptide hormone, as a central case study. PDD is described as an approach that screens compounds based on observable effects in cells, tissues, or whole organisms, without requiring prior knowledge of a specific molecular target. The authors contrast PDD with target-based drug discovery and argue that because disease definitions are largely symptom-based, therapeutic development can benefit from a phenotypic lens. The paper discusses how Tα1 has been evaluated in both preclinical and clinical settings, highlighting its complex immunomodulatory properties and its involvement in host-microbe metabolic interactions across multiple targets and metabolites. The authors also address challenges inherent to PDD, including hit validation and target deconvolution, and suggest that advances in big data analytics may help overcome these hurdles. The article further argues that Tα1's broad therapeutic utility can be meaningfully situated within the PDD framework and the modern precision medicine era. As a narrative review, it does not present original experimental data, and its conclusions are shaped by the selection and interpretation of existing literature.
Frontiers in medicine · Jun 2024DOI ↗ Review
This review article examines the evolving landscape of glucagon-like peptide-1 (GLP-1)-based therapies for obesity management. The authors describe how obesity, a major risk factor for type 2 diabetes and cardiovascular disease, often resists traditional lifestyle interventions, motivating the development of more targeted pharmacological approaches. The review focuses on incretin mimetics — drugs that mimic nutrient-stimulated hormones — which act on G-protein-coupled receptors including GLP-1, glucose-dependent insulinotropic polypeptide (GIP), and glucagon receptors. Specific agents highlighted include semaglutide and tirzepatide, as well as emerging multiagonist compounds such as GLP-1/glucagon and GIP/GLP-1/glucagon receptor co-agonists. The authors argue that glucagon receptor activation in particular represents a meaningful frontier in the field. The review surveys clinical efficacy data, neuroendocrine mechanisms, and signaling pathways underlying these therapies, while also outlining remaining challenges and future research directions. As a narrative review, it synthesizes existing literature rather than presenting original trial data, and does not conduct a formal meta-analysis. Its conclusions are therefore dependent on the quality and selection of the underlying primary studies reviewed.
Endocrinology and metabolism (Seoul, Korea) · Apr 2024DOI ↗ Review
This review paper examines the landscape of FDA-approved peptide therapeutics, tracing the field's evolution from the discovery of insulin in 1921 to approximately 100 subsequently authorized peptide drugs. The author focuses on six key peptide classes: glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) analogues for diabetes management, growth-hormone-releasing hormone (GHRH) analogues, cholecystokinin (CCK) analogues, adrenocorticotropic hormone (ACTH) analogues, and α-melanocyte-stimulating hormone (α-MSH) analogues. For each class, the review describes the native peptide's biological structure and mechanism of action, the medicinal chemistry strategies used to engineer synthetic analogues (such as modifications that extend half-life and reduce dosing frequency), the developmental and regulatory journey toward FDA approval, and known adverse effects. The paper highlights how targeted chemical modifications—including structural stabilization techniques—have improved the therapeutic utility of naturally derived peptides beyond their endogenous counterparts. Limitations include those inherent to any narrative review: no systematic search methodology or meta-analytic statistics are reported, and no original clinical or experimental data are generated. The work serves primarily as an educational synthesis of existing literature.
Biomolecules · Feb 2024DOI ↗ Review
This review article summarizes discussions from a round table held at the European Society for Sexual Medicine (ESSM) meeting in Rotterdam (February 2023), where leading experts addressed the diagnosis and treatment of hypoactive sexual desire disorder (HSDD) in premenopausal women. The authors note that HSDD is the most prevalent female sexual disorder, reported by approximately 28% of the estimated 40% of premenopausal women experiencing sexual dysfunction. The review covers the multifactorial nature of HSDD, encompassing biological, psychological, and sociocultural dimensions—including depression, sexual abuse history, gender-based "pleasure gaps," and structural inequalities. Regarding pharmacotherapy, the authors note that flibanserin and bremelanotide are the only FDA-approved treatments in the USA, while no medications are approved in Europe; compounds such as Lybrido, Lybridos, and Lorexys remain under development. The review reports that evidence supports combining pharmacological and psychosocial approaches, though clinician opinion remains divided. It also highlights that some women express a clear desire for access to drug-based options. A key limitation is that this article is expert opinion and narrative review rather than a systematic review or primary study, limiting the strength of its evidence base.
Pharmacology · Dec 2023DOI ↗ Review
This comprehensive review examines Hypoactive Sexual Desire Disorder (HSDD) in women, covering its etiology, diagnosis, treatment, and societal implications. The authors explore biological contributors — including hormonal fluctuations and neurotransmitter imbalances — alongside psychological factors such as stress, body image, and relationship dynamics, and sociocultural influences including media and cultural norms. Diagnostic criteria from DSM-5 and self-report assessment tools are reviewed to aid accurate identification and differentiation from other sexual disorders. The review surveys a broad spectrum of treatment options: non-pharmacological approaches (cognitive-behavioral therapy, sex therapy, couples therapy), pharmacological interventions (hormone therapy, SSRIs), and novel agents such as flibanserin and bremelanotide, as well as integrative strategies combining psychotherapy with lifestyle modification. The authors also address ongoing controversies, including lack of diagnostic consensus, concerns about medicalizing female sexuality, and ethical questions around pharmaceutical promotion. Future research directions highlighted include advances in neurobiology, personalized medicine, long-term outcome studies, and destigmatization efforts. As a narrative review, this paper synthesizes existing literature rather than generating new primary data, and is therefore subject to the limitations of selective source inclusion and potential author bias.
Review
This review examines the role of zonulin — a protein regulator of tight junctions in intestinal epithelial cells — in the context of the microbiota-gut-brain axis. The authors synthesize evidence from the past decade linking gut dysbiosis to increased intestinal permeability, whereby bacterial fragments and toxins enter systemic circulation, trigger local and systemic inflammation, and ultimately affect the brain. The review discusses how zonulin may also influence blood-brain barrier integrity, suggesting a dual role in both gut and neurological health. The authors survey potential pharmaceutical strategies targeting zonulin-associated pathways, including larazotide acetate and various zonulin receptor agonists and antagonists. Notably, the review also raises important methodological concerns, including inconsistent and potentially misleading nomenclature surrounding "zonulin" in the literature, as well as unresolved questions about the protein's exact molecular sequence. As a narrative review, it does not present new experimental data and is subject to selection bias. Its strength lies in synthesizing emerging findings and clearly identifying open scientific questions, making it a useful conceptual reference but not a source of direct clinical evidence.
International journal of molecular sciences · Apr 2023DOI ↗ Review
This paper is a narrative review evaluating bremelanotide (Vyleesi), a melanocortin receptor agonist delivered by injection, for the treatment of hypoactive sexual desire disorder (HSDD) in premenopausal women. The authors conducted a PubMed literature search of peer-reviewed publications and synthesized available evidence on the drug's proposed mechanism of action, pharmacokinetics, efficacy, and safety profile. The review notes that bremelanotide is thought to work by activating central melanocortin signaling pathways that may enhance sexual desire. Based on clinical trial data, the authors report that bremelanotide produced statistically significant improvements on validated questionnaires measuring sexual desire and distress; however, they characterize the overall clinical benefit as modest. The most commonly reported adverse event across trials was nausea, occurring in approximately 40% of participants. The authors caution that interpreting trial results is complicated by methodological challenges inherent to female sexual dysfunction research, including a pronounced placebo effect, long recall periods, and outcome measures susceptible to expectation bias. This paper does not present original trial data and relies on synthesis of existing literature, limiting its ability to independently confirm efficacy or safety claims.
Expert opinion on pharmacotherapy · Oct 2022DOI ↗ Review
This review paper traces more than a century of melanocortin research, from the initial discovery of melanocortins in 1916 to contemporary therapeutic applications. It describes the five known melanocortin receptors (MC1R–MC5R), with particular attention to the two neural receptors—MC3R and MC4R—which are predominantly expressed in the central nervous system and play key roles in regulating energy homeostasis. The authors systematically categorize ligands for these receptors into three groups: classical ligands (endogenous melanocyte-stimulating hormones and agouti-related peptide), nonclassical ligands (lipocalin 2, β-defensins, small molecules, and pharmacoperones), and clinically approved or repurposed agents (ACTH, setmelanotide, bremelanotide, and certain repurposed drugs). The review highlights how early medicinal chemistry efforts modifying endogenous peptides yielded potent and selective tool compounds, and how targeting neural MCRs has emerged as a viable strategy for metabolic conditions such as obesity and cachexia. Limitations inherent to this paper include its review design—it synthesizes existing literature rather than generating new experimental data—and therefore cannot independently establish clinical efficacy or safety for any specific ligand.
Biomolecules · Oct 2022DOI ↗ Review
This paper critically examines the regulatory approval of two FDA-approved drugs for hypoactive sexual desire disorder (HSDD) in women: flibanserin (Addyi, approved 2015) and bremelanotide (Vyleesi, approved 2019). The authors analyze the clinical trial data and outcome measures underpinning each approval. They report that clinical trials for flibanserin showed an average of only approximately one additional enjoyable sexual experience every two months compared to placebo, while bremelanotide trials showed no such numerical gain. The paper also highlights concerns about shifts in primary outcome measures during trials, a contested diagnostic indication, and the influence of a politicized, industry-sponsored patient advocacy campaign on flibanserin's approval—which succeeded on its third regulatory attempt. The authors argue that bremelanotide's approval, despite even weaker efficacy evidence, was facilitated by the regulatory precedent set by flibanserin. The paper calls for reconsideration of these approvals and recommends reforms to better manage conflicts of interest and define clinically meaningful benefit in future regulatory decisions. A key limitation is that this is an opinion/review piece rather than an original clinical study, and does not present new primary data.
Drug and therapeutics bulletin · Oct 2021DOI ↗ Review
This systematic review examines the role of the zonulin pathway in regulating tight junction integrity and its contribution to increased epithelial and endothelial permeability across a range of chronic and acute inflammatory conditions. The authors searched PubMed and Google Scholar using terms related to Larazotide (also known as AT-1001, FZI/0, and INN-202), retrieving 209 publications, which were then filtered for relevance and English language. Findings were organized by disease area, including celiac disease, type 1 diabetes, other autoimmune diseases, inflammatory bowel disease, Kawasaki disease, respiratory diseases (both infectious and non-infectious), and miscellaneous conditions. The review concludes that evidence from both in vivo and in vitro studies supports a substantial role for zonulin dysregulation in these diseases, and suggests Larazotide — a zonulin antagonist — as a potentially viable therapeutic strategy. The authors also highlight newly identified molecular targets for Larazotide. Key limitations include the heterogeneity of the underlying studies (spanning animal models, in vitro work, and human trials of varying quality), and the review's broad scope may obscure differences in evidence quality across disease indications.
Current medicinal chemistry · Jan 2021DOI ↗ Review
This narrative review examines the potential adjunctive role of growth hormone secretagogues (GHS) in managing body composition changes associated with male hypogonadism and metabolic syndrome. The authors acknowledge that while testosterone replacement therapy remains the standard of care for hypogonadism, its body composition benefits are inconsistent across patient populations. The review surveys existing literature on five GHS compounds — sermorelin, GHRP-2, GHRP-6, ibutamoren (MK-677), and ipamorelin — noting that all stimulate growth hormone (GH) and insulin-like growth factor-1 (IGF-1) secretion and may improve body composition metrics such as reducing fat mass and attenuating muscle atrophy. The authors also explore their potential utility in eugonadal males with metabolic syndrome or subclinical hypogonadism. A major limitation explicitly acknowledged by the authors is the scarcity of robust clinical trial data evaluating these compounds specifically in hypogonadal men. The review concludes that while GHS show theoretical and preliminary promise as complementary agents, the current evidence base is insufficient to draw firm clinical conclusions, and the authors call for future controlled investigations. No new primary data are presented.
Translational andrology and urology · Mar 2020DOI ↗ Review
This review paper examines the biological pathway linking growth hormone releasing peptides (GHRPs) — with a focus on the peptide hexarelin — to metabolic regulation via the scavenger receptor CD36 and the nuclear receptor PPARγ. The authors summarize evidence showing that GHRPs can activate PPARγ through CD36, and discuss how this pathway may influence key metabolic processes including atherosclerosis, hepatic cholesterol biosynthesis, and mitochondrial biogenesis in fat tissue. The paper also discusses the role of the PPARγ coactivator PGC-1 in mediating these downstream effects. The authors contextualize this pathway alongside established pharmacological approaches, such as thiazolidinediones, which also target PPARγ to improve insulin resistance in diabetic patients. The paper proposes that the GHRP-CD36-PPARγ axis represents a novel potential target for addressing metabolic disorders. As a review, the paper synthesizes existing preclinical and some clinical research but does not present original experimental data. Key limitations include the absence of new human trial data and the largely preclinical nature of much of the underlying evidence for hexarelin specifically.
International journal of molecular sciences · May 2018DOI ↗