Page last updated: 2024-11-13

adrenomedullin

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth

Description

Adrenomedullin: A 52-amino acid peptide with multi-functions. It was originally isolated from PHEOCHROMOCYTOMA and ADRENAL MEDULLA but is widely distributed throughout the body including lung and kidney tissues. Besides controlling fluid-electrolyte homeostasis, adrenomedullin is a potent vasodilator and can inhibit pituitary ACTH secretion. [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID91976826
MeSH IDM0216201

Synonyms (1)

Synonym
adrenomedullin

Research Excerpts

Toxicity

ExcerptReferenceRelevance
"Administration of adrecizumab is safe and well tolerated in humans, both in the absence and presence of systemic inflammation."( Safety, tolerability and pharmacokinetics/pharmacodynamics of the adrenomedullin antibody adrecizumab in a first-in-human study and during experimental human endotoxaemia in healthy subjects.
Blet, A; Geven, C; Kox, M; Mebazaa, A; Peelen, R; Pickkers, P; Ten Elzen, B; van Lier, D, 2018
)
0.48
" Adverse events (AEs), vital signs, physical examinations, laboratory tests, electrocardiograms (ECG), and pharmacokinetics were assessed."( Safety, Tolerability, and Pharmacokinetics of Adrenomedullin in Healthy Males: A Randomized, Double-Blind, Phase 1 Clinical Trial.
Kaji, Y; Kita, T; Kitamura, K, 2020
)
0.56
" MEL weakened the toxic effects of DOX on the cardiac tissue and it is shown histologically."( Effects of Melatonin and Adrenomedullin in Reducing the Cardiotoxic Effects of Doxorubicin in Rats.
Bahceci, SA; Durdagi, G; Oyar, EO; Ozbek, M; Pehlivan, DY, 2021
)
0.62
" Primary safety (90-day mortality, treatment emergent adverse events (TEAE)) and tolerability (drug interruption, hemodynamics) endpoints were recorded."( Safety and tolerability of non-neutralizing adrenomedullin antibody adrecizumab (HAM8101) in septic shock patients: the AdrenOSS-2 phase 2a biomarker-guided trial.
Bauer, M; Beishuizen, A; Bergmann, A; Chousterman, B; Contou, D; Dugernier, T; François, B; Godet, T; Hartmann, O; Helms, J; Hoiting, O; Huberlant, V; Karakas, M; Lacherade, JC; Lascarrou, JB; Laterre, PF; Marx, G; Mebazaa, A; Meziani, F; Oueslati, H; Pars, M; Pickkers, P; Pottecher, J; Richter, K; Schuerholz, T; Wittebole, X; Zimmermann, J, 2021
)
0.62

Pharmacokinetics

ExcerptReferenceRelevance
" PK analyses showed proportional increases in the maximum plasma concentration of adrecizumab with increasing doses, a small volume of distribution, a low clearance rate and a terminal half-life of ~14 days."( Safety, tolerability and pharmacokinetics/pharmacodynamics of the adrenomedullin antibody adrecizumab in a first-in-human study and during experimental human endotoxaemia in healthy subjects.
Blet, A; Geven, C; Kox, M; Mebazaa, A; Peelen, R; Pickkers, P; Ten Elzen, B; van Lier, D, 2018
)
0.48
" The present study aimed to evaluate the pharmacodynamic properties and safety of AM in healthy male adults in a phase 1 clinical trial."( Safety, Tolerability, and Pharmacokinetics of Adrenomedullin in Healthy Males: A Randomized, Double-Blind, Phase 1 Clinical Trial.
Kaji, Y; Kita, T; Kitamura, K, 2020
)
0.56
" Pharmacokinetic analysis revealed that elevated plasma AM in RD-Ag rats may be caused by a reduced volume of distribution."( Plasma Clearance of Intravenously Infused Adrenomedullin in Rats with Acute Renal Failure.
Hosoda, H; Nakamura, T; Yoshihara, F, 2022
)
0.72

Compound-Compound Interactions

ExcerptReferenceRelevance
" Inhaled nitric oxide combined with prostacyclin or ADM was more effective than nitric oxide alone in lowering PAP and improving oxygenation."( Inhaled nitric oxide combined with prostacyclin and adrenomedullin in acute respiratory failure with pulmonary hypertension in piglets.
Buonocore, G; Corsini, I; Dani, C; Forestieri, A; Giannesello, L; Gori, G; Gritti, G; Longini, M; Paternostro, F; Pavoni, V; Perna, A; Rubaltelli, FF, 2007
)
0.34
" In order to reduce rat proteins to elicit possible immune responses in humans, we determined the effect of human AM combined with human AMBP-1 after intestinal ischemia and reperfusion (I/R)."( Human adrenomedullin combined with human adrenomedullin binding protein-1 is protective in gut ischemia and reperfusion injury in the rat.
Blau, SA; Wang, P; Wu, R; Zhang, F; Zhou, M, 2009
)
0.35
" Here we investigate whether proadrenomedullin N-terminal 20 peptide (PAMP), a naturally occurring peptide of the skin with antimicrobial and proangiogenic properties, either alone or in combination with autologous skeletal muscle stem/progenitor cells, acts as a wound healing factor."( The angiogenesis promoter, proadrenomedullin N-terminal 20 peptide (PAMP), improves healing in both normoxic and ischemic wounds either alone or in combination with autologous stem/progenitor cells.
Bellón, JM; Buján, J; Cifuentes, A; García-Honduvilla, N; Martínez, A, 2013
)
0.39

Bioavailability

ExcerptReferenceRelevance
" AM infusion also upregulated the gene expression of guanosine-5'-triphosphate cyclohydrolase I and downregulated the expression of p22(phox), suggesting that AM increased the NOS coupling and bioavailability of NO."( Beyond vasodilation: the antioxidant effect of adrenomedullin in Dahl salt-sensitive rat aorta.
Cao, YN; Chen, AF; Eto, T; Kato, J; Kawano, J; Kitamura, K; Kuwasako, K; Nagoshi, Y; Suganuma, T; Tsuruda, T; Wada, A; Yanagita, T, 2005
)
0.33
" These data provide the first evidence that AM increases NO bioavailability in intact murine myocardium and confirm that the NO/sGC/cGMP pathway is central to the cytoprotective action of AM against ischaemia-reperfusion injury."( Nitric oxide/cGMP signalling mediates the cardioprotective action of adrenomedullin in reperfused myocardium.
Baxter, GF; Drexhage, C; Fowkes, RC; Hamid, SA; Rassaf, T; Thompson, I; Totzeck, M, 2010
)
0.36
"Atypical 7-transmembrane receptors, often called decoy receptors, act promiscuously as molecular sinks to regulate ligand bioavailability and consequently temper the signaling of canonical G protein-coupled receptor (GPCR) pathways."( Decoy receptor CXCR7 modulates adrenomedullin-mediated cardiac and lymphatic vascular development.
Bautch, VL; Caron, KM; Dunworth, WP; Espenschied, ST; Hoopes, SL; Karpinich, NO; Klein, KR; Kushner, EJ; Willcockson, HH, 2014
)
0.4
" Detailed information on the binding mode of ADM from a recently reported crystal structure as well as efforts to improve its plasma stability and bioavailability may help to overcome these limitations in the future."( Adrenomedullin - new perspectives of a potent peptide hormone.
Beck-Sickinger, AG; Els-Heindl, S; Schönauer, R, 2017
)
0.46
" The bioavailability of HSA-AM compared with that of adrenomedullin was much improved after subcutaneous administration in the rat, which was probably due to the superior resistance of HSA-AM towards endogenous proteases and its reduced clearance from the blood."( Development of a novel human adrenomedullin derivative: human serum albumin-conjugated adrenomedullin.
Akashi, E; Ashizuka, S; Kato, J; Kitamura, K; Kuroishi, N; Nagata, S; Yamasaki, M, 2021
)
0.62

Dosage Studied

Adrenomedullin inhibits calcium-induced amylase secretion by reducing calcium sensitivity of the pancreatic exocytotic machinery. In streptolysin-O permeabilized acini, 10 nM adrenomedull in shifted the calcium dose-response curve to the right. Studies in genetic animal models have revealed the critical importance of adrenomedully dosage at the maternal-fetal interface.

ExcerptRelevanceReference
" This study examined the dose-response effects of adrenomedullin (rat, 11-50) on mean arterial pressure (MAP), heart rate (HR), renal blood flow (RBF), glomerular filtration rate (GFR) and renal tubular electrolyte excretion in Inactin-anaesthetized Sprague Dawley rats."( Effects of calcitonin gene-related peptide receptor antagonists on renal actions of adrenomedullin.
Elhawary, AM; Pang, CC; Poon, J, 1995
)
0.29
" In streptolysin-O permeabilized acini, 10 nM adrenomedullin shifted the calcium dose-response curve to the right, indicating that adrenomedullin inhibits calcium-induced amylase secretion by reducing calcium sensitivity of the pancreatic exocytotic machinery."( Inhibition of stimulated amylase secretion by adrenomedullin in rat pancreatic acini.
Fujita, T; Mine, T; Ohnishi, H; Tanaka, Y; Tsuchida, T, 1999
)
0.3
" The dose-response curve of this effect showed a maximal response with 10(-7) M ADM."( The paradoxical effect of adrenomedullin on Na+ transport by the renal distal tubule luminal membrane.
Brunette, MG; Leclerc, M, 2000
)
0.31
" Ang II was administered ip at a dosage of 640 ng/kg."( Angiotensin II-induced insulin resistance is enhanced in adrenomedullin-deficient mice.
Ando, K; Asano, T; Fujita, T; Itakura, K; Matsui, H; Ogihara, T; Qingyou, X; Shimosawa, T; Xing, G, 2004
)
0.32
" Furthermore, a dose-response study was performed with subcutaneous microvessels using the potent vasodilator, adrenomedullin."( Visualisation of morphological changes in living intact human microvessels using confocal microscopy.
Campbell, S; Daly, CJ; Hamid, SA; Howe, DC, 2005
)
0.33
" To select the genes that may be regulated by estrogen, we treated mice with several doses of estrogen and searched for those genes whose dose-response expression pattern mirrored the uterine growth pattern."( The estrogen-responsive adrenomedullin and receptor-modifying protein 3 gene identified by DNA microarray analysis are directly regulated by estrogen receptor.
Chambon, P; Goto, M; Iguchi, T; Kobayashi, M; Krust, A; Takahashi, E; Watanabe, H, 2006
)
0.33
" Because of the potential clinical benefits of AM, indications for use and optimal dosing strategies should be established."( Pathophysiologic and therapeutic implications of adrenomedullin in cardiovascular disorders.
Ishimitsu, T; Matsuoka, H; Minami, J; Ono, H, 2006
)
0.33
" Rats treated with low dosage intermedin1-53 (5 nmol/kg/day, 2 days) showed 21% (P<0."( Intermedin1-53 protects the heart against isoproterenol-induced ischemic injury in rats.
Chang, JK; Geng, B; Gerns, H; Jia, YX; Pan, CS; Qi, YF; Tang, CS; Wen, JK; Xiao, Y; Yang, J; Yang, JH; Zhang, J; Zhao, J, 2006
)
0.33
" There was a dose-response relationship between VFs and BP status."( A pilot study on level of blood vasoactive factors in prehypertensive and hypertensive patients.
Liu, J; Liu, Y; Wang, Z; Wen, J; Wen, S; Wu, Z, 2008
)
0.35
" Results showed that administration of human AM/AMBP-1 reduced pro-inflammatory cytokines, attenuated organ injury, and improved the survival rate in a seemingly dose-response fashion."( Human adrenomedullin combined with human adrenomedullin binding protein-1 is protective in gut ischemia and reperfusion injury in the rat.
Blau, SA; Wang, P; Wu, R; Zhang, F; Zhou, M, 2009
)
0.35
" Dose-response studies revealed prominent effects of FG-4497 at a dose of 100 mg/kg as assessed by significant up-regulation of mRNA in both kidney and brain of the following HIF-dependent genes: vascular endothelial growth factor, adrenomedullin and erythropoietin."( Short-term effects of pharmacologic HIF stabilization on vasoactive and cytotrophic factors in developing mouse brain.
Arend, M; Gassmann, M; Keller, S; Krischke, G; Rascher, W; Schneider, C; Trollmann, R; Walkinshaw, G, 2009
)
0.35
" Therefore, we evaluated whether modulating adrenomedullin (Adm) gene dosage within tumor cells affects lymphangiogenesis."( Adrenomedullin gene dosage correlates with tumor and lymph node lymphangiogenesis.
Caron, KM; Espenschied, ST; Fedoriw, Y; Karpinich, NO; Kechele, DO; Willcockson, HH, 2013
)
0.39
" New insight has been gained regarding volume management, including dosing strategies for intravenous loop diuretics and the role of ultrafiltration in patients with heart failure and renal dysfunction."( Acute decompensated heart failure: update on new and emerging evidence and directions for future research.
Albert, NM; Butler, J; Carson, PE; Collins, SP; Colvin-Adams, M; Dimarco, JP; Ezekowitz, JA; Fang, JC; Givertz, MM; Hernandez, AF; Hershberger, RE; Katz, SD; Krishnamani, R; Rogers, JG; Spertus, JA; Starling, RC; Stevenson, WG; Stough, WG; Sweitzer, NK; Tang, WH; Teerlink, JR; Walsh, MN; Westlake Canary, CA, 2013
)
0.39
" Studies in genetic animal models have revealed the critical importance of adrenomedullin dosage at the maternal-fetal interface, with cells from both the maternal and fetal compartments contributing to essential aspects underlying appropriate uterine receptivity, implantation and vascular remodeling of spiral arteries."( Adrenomedullin and endocrine control of immune cells during pregnancy.
Caron, KM; Matson, BC, 2014
)
0.4
" Here, we provide the molecular underpinning for this proliferative phenotype by demonstrating that the dosage and signaling of adrenomedullin (Adm, gene; AM, protein)-a mitogenic peptide hormone required for normal cardiovascular development-is tightly controlled by CXCR7."( Decoy receptor CXCR7 modulates adrenomedullin-mediated cardiac and lymphatic vascular development.
Bautch, VL; Caron, KM; Dunworth, WP; Espenschied, ST; Hoopes, SL; Karpinich, NO; Klein, KR; Kushner, EJ; Willcockson, HH, 2014
)
0.4
"This phase I study (NCT01539889) evaluated the safety, efficacy, and dosing of PulmoBind for molecular imaging of pulmonary circulation."( Molecular imaging of the human pulmonary vascular endothelium using an adrenomedullin receptor ligand.
Cossette, M; Dupuis, J; Finnerty, V; Fournier, A; Harel, F; Létourneau, M; Levac, X; Marcil, S; Nguyen, QT, 2015
)
0.42
" Nociceptive behaviours and cumulative dose-response of morphine analgesia were assessed."( Contribution of adrenomedullin to the switch of G protein-coupled μ-opioid receptors from Gi to Gs in the spinal dorsal horn following chronic morphine exposure in rats.
Couture, R; Hong, Y; Huang, J; Li, Q; Wang, D; Zeng, J, 2016
)
0.43
" Of the 12 subjects in multiple dosing test, one from the AM group withdrew owing to a headache."( Safety, Tolerability, and Pharmacokinetics of Adrenomedullin in Healthy Males: A Randomized, Double-Blind, Phase 1 Clinical Trial.
Kaji, Y; Kita, T; Kitamura, K, 2020
)
0.56
" The aim of the study was to evaluate the diagnostic accuracy of sepsis defined by SIRS Criteria of 1991, Second Consensus Conference Criteria of 2001, modified Second Consensus Conference Criteria of 2001 (obtaining SIRS Criteria and SOFA score), Third Consensus Conference of 2016, in addition to the dosage of Procalcitonin (PCT) and MR-pro-Adrenomedullin (MR-proADM)."( Best diagnostic accuracy of sepsis combining SIRS criteria or qSOFA score with Procalcitonin and Mid-Regional pro-Adrenomedullin outside ICU.
Angeletti, S; Benvenuto, D; Caputo, D; Carnà, EPR; Ciccozzi, M; Costantino, S; De Florio, L; Fogolari, M; Nobile, E; Spoto, S; Valeriani, E, 2020
)
0.56
"Background and Objectives: The aim of this paper is to evaluate the impact of humoral substance mid-regional pro-adrenomedullin (MR-proADM) on the two-year survival of patients with chronic heart failure and relate it to the dosage of furosemide."( Relation between Mid-Regional Pro-Adrenomedullin in Patients with Chronic Heart Failure and the Dose of Diuretics in 2-Year Follow-Up-Data from FAR NHL Registry.
Benešová, K; Goldbergová-Pávková, M; Jarkovský, J; Krejčí, J; Lábr, K; Ludka, O; Málek, F; Ošťádal, P; Pařenica, J; Špinar, J; Špinarová, L; Špinarová, M, 2022
)
0.72
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (3,056)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's553 (18.10)18.2507
2000's1370 (44.83)29.6817
2010's891 (29.16)24.3611
2020's242 (7.92)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials131 (4.18%)5.53%
Reviews347 (11.07%)6.00%
Case Studies13 (0.41%)4.05%
Observational87 (2.78%)0.25%
Other2,557 (81.56%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (5)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
The Role of Adrenomedullin on the Outcome of Severe Heart Failure: a Clinical Randomized Study [NCT01154504]0 participants (Actual)Interventional2010-04-30Withdrawn(stopped due to We randomized 18 patients, but was impossible to measure adrenomedullin in Brazil. However, we analysed some interesting clinical and laboratorial results.)
A First-in-human, Double-blind, Placebo-controlled, Phase 1 Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Single and Multiple Intravenous Doses of HM201 (Pegylated Human Adrenomedullin) in Healthy Subjects (Adults) [NCT05088369]Phase 153 participants (Actual)Interventional2021-11-11Completed
Adrenomedullins Headache Inducing Effects on Migraine Without Patients [NCT04111484]20 participants (Actual)Interventional2019-09-28Completed
Role of Adrenomedullin in Leukemic Endosteal/Vascular Niches [NCT04460963]72 participants (Anticipated)Interventional2021-06-09Recruiting
A Multicenter, Single-arm, Clinical Trial of Adrenomedullin for Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy [NCT06072118]Phase 260 participants (Actual)Interventional2022-01-06Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]