Trial reportBritish journal of pharmacology1996
The increase in human plasma immunoreactive endothelin but not big endothelin-1 or its C-terminal fragment induced by systemic administration of the endothelin antagonist TAK-044.
Trial report in British journal of pharmacology, 1996. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed, 65 citations in OpenAlex.
- Comparison of the pharmacokinetics, pharmacodynamics and tolerability of tezosentan between caucasian and Japanese subjects.British journal of clinical pharmacology · 2006Trial
- Direct comparison of selective endothelin A and non-selective endothelin A/B receptor blockade in chronic heart failure.Heart (British Cardiac Society) · 2005Trial
- Pharmacokinetics and pharmacodynamics of tezosentan, an intravenous dual endothelin receptor antagonist, following chronic infusion in healthy subjects.British journal of clinical pharmacology · 2002Trial
- Endogenous endothelin maintains coronary artery tone by endothelin type A receptor stimulation in patients undergoing coronary arteriography.Heart (British Cardiac Society) · 2000Trial
- Pharmacokinetics and pharmacodynamic effects of ABT-627, an oral ETA selective endothelin antagonist, in humans.British journal of clinical pharmacology · 2000Trial
- Apelin is expressed throughout the human kidney, is elevated in chronic kidney disease & associates independently with decline in kidney function.British journal of clinical pharmacology · 2022Article
- Renin-Angiotensin and Endothelin Systems in Patients Post-Takotsubo Cardiomyopathy.Journal of the American Heart Association · 2022Article
- Orthogonal Peptide-Templated Labeling Elucidates Lateral ETChembiochem : a European journal of chemical biology · 2022Article
- Pulmonary hypertension: Proteins in the blood.Global cardiology science & practice · 2020Review
- Endothelin.Pharmacological reviews · 2016Review
- Endothelin receptors and their antagonists.Seminars in nephrology · 2015Review
- Endothelin@25 - new agonists, antagonists, inhibitors and emerging research frontiers: IUPHAR Review 12.British journal of pharmacology · 2014Review
- Contrasting actions of endothelin ET(A) and ET(B) receptors in cardiovascular disease.Annual review of pharmacology and toxicology · 2007Review
- Clinical pharmacology of bosentan, a dual endothelin receptor antagonist.Clinical pharmacokinetics · 2004Review
- Structural basis of the function of endothelin receptor.Molecular and cellular biochemistry · 1999Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 4 institutions in 1 country.
Funding
Abstract
1. We examined the effects of systemic infusion, in healthy human volunteers, of the endothelin antagonist TAK-044 on the plasma concentrations of mature endothelin, big endothelin-1 and the C-terminal fragment of big endothelin-1, by selective solid-phase extraction and specific radioimmunoassays. 2. Unlabelled TAK-044 competed with specific [125I]-endothelin-1 binding to human left ventricle tissue in a biphasic manner giving KD values of 0.11 nM and 26.8 nM at the ETA and ETB receptor subtypes, respectively, indicating a 244 fold selectivity for the ETA receptor subtype. 3. A 15 min intravenous infusion of placebo or 30 mg TAK-044 (giving a serum concentration of 2 nM, calculated to block > 95% of ETA but < 5% ETB receptors) had no effect on the immunoreactive plasma concentrations of the three peptides. 4. At the higher dose of 750 mg TAK-044 (giving a serum concentration of 80 nM, calculated to block > 99% of ETA and > 75% ETB receptors), the immunoreactive plasma endothelin concentrations were increased 3.3 fold over basal levels (P < 0.01). The concentrations of big endothelin-1 or C-terminal fragment of big endothelin-1 were unchanged. 5. At both doses of TAK-044, there were significant decreases in diastolic blood pressure, and peripheral vascular resistance, with corresponding increases in cardiac index and stroke index. There were no changes in systolic or mean arterial blood pressures or heart rate. 6. Since only the concentrations of the mature peptide were increased, we conclude that the most likely sources of endothelin contributing to the observed rise were displacement of receptor-bound peptide and reduction in plasma clearance rather than peptide synthesis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.