Relaxin

Relaxin-2 (the main circulating human form, gene RLN2); serelaxin = recombinant human relaxin-2, development codes RLX030 / Reasanz (proposed brand name, never licensed)

Cardiovascular & circulation

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Summary

Class: Naturally occurring two-chain peptide hormone of the insulin/relaxin superfamily, linked by disulphide bonds (53 amino acids across the A and B chains)
Mechanism: Activates the RXFP1 receptor to widen blood vessels, increase blood flow to the kidney, and suppress fibrosis — a hormone that remodels connective tissue
Routes studied: Continuous intravenous infusion (all the major trials); subcutaneous in some earlier studies
Half-life: Short in plasma (minutes to a few hours), hence the continuous-infusion design
Storage: Recombinant protein; investigational material handled refrigerated under pharmacy control
Regulatory status: Not approved anywhere. The FDA and EMA declined approval, and development was discontinued after RELAX-AHF-2 †

Doses are as reported in studies or by the community — never recommendations.

1What it is

Relaxin was discovered in the 1920s as the hormone that loosens the pelvic ligaments in pregnancy — hence the name. In humans, relaxin-2 rises in pregnancy and does far more than soften ligaments: it raises cardiac output, increases renal blood flow and reduces vascular resistance, which is part of how a pregnant circulation accommodates a second person. It is also one of the body's few genuinely anti-fibrotic signals.

That combination made it an obvious candidate for acute heart failure, where the problem is congestion, stiff vessels and a struggling kidney. Serelaxin, the recombinant version, became one of the most closely watched cardiovascular drug programmes of the 2010s — and one of the more instructive failures. It is not a community compound: it was only ever given as a 48-hour hospital infusion. Community use: essentially none documented.

2How it's thought to work

Activates RXFP1 (relaxin family peptide receptor 1), a G-protein-coupled receptor, raising cAMP and nitric oxide.

Produces vasodilation that is systemic and includes the renal circulation, increasing renal plasma flow and glomerular filtration — unusual among vasodilators, which often compromise the kidney.

Anti-fibrotic. downregulates TGF-β signalling, reduces collagen synthesis and increases matrix metalloproteinase activity, in effect telling tissue to stop laying down scar.

Increases vascular compliance (arteries become less stiff), which is distinct from simply lowering pressure.

Has anti-inflammatory and anti-apoptotic effects in organ-injury models.

Relaxin at the RXFP1 receptor. The vessel widens and renal blood flow rises, while the collagen being laid down in tissue thins out — a vasodilator and a brake on fibrosis from the same receptor.Schematic — not to scale

3What the research shows

Graded A (positive)

Acute heart failure, Phase 2

Pre-RELAX-AHF, a dose-finding randomised trial, suggested the 30 µg/kg/day dose relieved dyspnoea and reduced worsening heart failure (Teerlink 2009, Lancet). [1]

Graded A (mixed)

Acute heart failure, RELAX-AHF

RELAX-AHF (n≈1,161) met one of two co-primary dyspnoea endpoints (VAS area under the curve) and missed the other, and showed no difference in the 60-day outcomes it was powered for. What drew attention was a secondary, unexpected finding: a reduction in 180-day all-cause and cardiovascular mortality of roughly a third (Teerlink 2013, Lancet). A 48-hour infusion improving six-month survival was biologically surprising, and the field treated it as a hypothesis to test rather than a result to act on. [2]

Graded A (negative)

Acute heart failure, RELAX-AHF-2

The confirmatory trial enrolled approximately 6,500 patients and failed both primary endpoints: no reduction in 180-day cardiovascular death, and no reduction in worsening heart failure through day 5 (Metra 2019, NEJM). The mortality signal from RELAX-AHF did not reproduce. Development for this indication ended. This is the single most important fact about serelaxin, and a textbook illustration of why a striking secondary endpoint is not a finding. [3]

Graded A (negative)

Systemic sclerosis (scleroderma)

Recombinant relaxin was tested for skin fibrosis in systemic sclerosis on the anti-fibrotic rationale. A randomised placebo-controlled trial found no benefit on modified Rodnan skin score, and there were renal safety concerns on withdrawal (Khanna 2009, Arthritis Rheum; earlier Seibold 2000, Ann Intern Med). [4][5]

Portal hypertension, cirrhosis and kidney disease

Small human studies report increased renal and hepatic blood flow and reduced portal pressure, consistent with mechanism. Exploratory only.

Cardiac and renal fibrosis, pre-eclampsia models

Consistent anti-fibrotic and vasoprotective findings in rodents across heart, kidney and lung models. The gap between this animal literature and RELAX-AHF-2 is itself an open research question.

4Reported side effects and interactions

Literature-reported

In the large trials serelaxin was well tolerated. The most common finding was hypotension, expected from a vasodilator and the usual reason for dose reduction or stopping the infusion. Rates of renal and hepatic adverse events were not increased versus placebo in RELAX-AHF-2; serum creatinine actually tended to improve on treatment.

Community-reported

None. Not in self-directed use.

Theoretical. Relaxin's connective-tissue effects are the reason pregnant ligaments loosen; what sustained exposure would do to tendon and joint integrity in a non-pregnant person has never been studied, and this is the obvious caution against any informal use. Anti-fibrotic signalling also overlaps with tissue-remodelling pathways relevant to tumour invasion.

Interactions. Additive hypotension with nitrates, ACE inhibitors, ARBs, sacubitril/valsartan and diuretics. No formal interaction studies beyond trial co-medication analyses.

Markers researchers commonly monitor

These follow the trial protocols:

Marker	Why it's watched
Blood pressure, frequently during infusion	hypotension is the dose-limiting effect and triggered protocol dose reductions.
Serum creatinine and eGFR	renal function was a key endpoint, and uniquely for a vasodilator it tended to improve.
NT-proBNP	congestion and wall-stress marker; fell more on serelaxin in RELAX-AHF.
Liver enzymes (ALT/AST)	monitored in the trials; no excess signal emerged.
Troponin	markers of myocardial injury were tracked as part of the organ-protection hypothesis.
Body weight and fluid balance	standard in acute heart failure for decongestion.
Relaxin levels	research assays only; not clinically available.

Free for everyone. Safety information is never behind a paywall.

5Reconstitution and handling

Not applicable as a consumer practice. Serelaxin was supplied as investigational material for dilution and continuous intravenous infusion over 48 hours under blood-pressure monitoring, with protocol rules for reducing or stopping the infusion if systolic pressure fell. There is no vial format, no regimen in general use, and no calculator preset.

6Commonly studied alongside

In the heart-failure literature it is discussed next to nesiritide (recombinant BNP — another acute-heart-failure vasodilator that failed its confirmatory trial), urocortin 2 (#155), adrenomedullin (#151) and ularitide. Relaxin-3 and the RXFP3 receptor are a separate neuroscience story, not a cardiovascular one.

Informational cross-links. Not stack recommendations.

7Regulatory status by region

Region	Status (checked —)
United States	Not FDA-approved. FDA advisory review did not support approval; programme discontinued after RELAX-AHF-2 †
European Union	Not authorised; the proposed name Reasanz was never licensed †
United Kingdom	Not licensed
Australia	Not approved
South Africa	Not registered
Sport	Not specifically listed by WADA. As a non-approved peptide hormone it would fall under S0 if used. Check the current list

8Open questions

Why did the RELAX-AHF mortality signal vanish in a trial six times the size — chance, population differences, or background therapy?
Is the anti-fibrotic effect real in humans over months, where no adequate trial has tested it?
Would relaxin help in portal hypertension or chronic kidney disease, where mechanism and early data align better than in acute heart failure?
What are the musculoskeletal consequences of sustained RXFP1 activation outside pregnancy?

9References

1Teerlink JR et al. (2009). Relaxin for the treatment of patients with acute heart failure (Pre-RELAX-AHF): a multicentre, randomised, placebo-controlled, parallel-group, dose-finding phase IIb study. Lancet. PubMed · DOI
2Teerlink JR et al. (2013). Serelaxin, recombinant human relaxin-2, for treatment of acute heart failure (RELAX-AHF): a randomised, placebo-controlled trial. Lancet. PubMed · DOI
3Metra M et al. (2019). Effects of serelaxin in patients with acute heart failure (RELAX-AHF-2). NEJM. PubMed · DOI
4Seibold JR et al. (2000). Recombinant human relaxin in the treatment of scleroderma: a randomized, double-blind, placebo-controlled trial. Ann Intern Med. PubMed · DOI
5Khanna D et al. (2009). Recombinant human relaxin in the treatment of systemic sclerosis with diffuse cutaneous involvement. Arthritis Rheum. PubMed
6Bathgate RAD et al. (2013). Relaxin family peptides and their receptors. Physiol Rev. PubMed · DOI
7Conrad KP (2011). Maternal vasodilation in pregnancy: the emerging role of relaxin. Am J Physiol Regul Integr Comp Physiol. PubMed · DOI

References are being resolved to PubMed/DOI identifiers; links search PubMed for the citation until then.

† Being confirmed by our reviewers against current sources.

10Community

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Self-reported side effects Phase 2

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11Page history

30 Oct 2026Profile published — awaiting medical review

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