Teprotide
The pit-viper venom peptide that proved blocking angiotensin-converting enzyme lowers blood pressure, and the model for captopril
Teprotide is a nine-amino-acid peptide first found in the venom of the Brazilian pit viper Bothrops jararaca and later made synthetically under the code SQ 20881. It blocks angiotensin-converting enzyme (ACE), the step that turns angiotensin I into the blood-pressure-raising angiotensin II. In the 1970s it was injected into people with high blood pressure, heart failure and other conditions, mostly as a test of how much their blood pressure depended on renin. It worked only by injection and was scarce, so it was never marketed; its success drove the design of the oral drug captopril.
Used in human trials: 1 mg/kg, Single injection, Intravenous (Study: salt-replete hypertension, 9 patients) Details ↓
Recommended Dosing
Used in human trials
No manufacturer dose exists for this use: these are amounts given in published trials, not recommendations.
What is it?
Teprotide belongs to a family of short, proline-rich peptides in the venom of Bothrops jararaca, a Brazilian pit viper. These peptides were first noticed because they made the body's own bradykinin act more strongly, which is why teprotide is also called bradykinin-potentiating peptide 9a. The reason turned out to be an enzyme: the same converting enzyme that breaks bradykinin down also turns angiotensin I into angiotensin II. A synthetic version, coded SQ 20881, was used in nearly every study of it.
In the test tube teprotide binds angiotensin-converting enzyme tightly. Kinetic work on the purified bovine kidney enzyme gave an inhibition constant of about 2.5 nanomolar, and later comparisons in dog blood vessels found it a more potent blocker of angiotensin I conversion than captopril. In perfused rat mesenteric vessels it also slowed the breakdown of bradykinin at concentrations that did not stop angiotensin conversion, part of a debate in the 1980s about which of the enzyme's two jobs mattered most for lowering blood pressure.
In people, teprotide was given as a single intravenous injection, usually around 1 mg/kg. Its effect depended on renin. In patients with high-renin hypertension it cut mean arterial pressure by about 19% by relaxing the arteries, against about 10% in normal-renin hypertension and no change in people with normal blood pressure. Doctors used this as a diagnostic test: a large fall after an injection pointed to renin-driven hypertension, such as narrowing of a kidney artery, and helped choose surgery or drug treatment. In 18 hypertensive emergencies, the response to 1 mg/kg sorted patients into those who should get a beta-blocker and those who needed diuretics and salt restriction.
Studies also looked beyond blood pressure. After heart surgery it lowered pressure in the lung circulation, in proportion to the patient's renin; in severe heart failure it reduced the work of the heart without starving the heart muscle of oxygen; and in healthy volunteers it lowered blood pressure without blunting the normal response to standing or hand-grip exercise. In women whose blood pressure stayed high after pre-eclampsia, it had no effect until a diuretic had been given, which suggested their high pressure did not depend on angiotensin II.
Teprotide was never developed into a medicine. It had to be injected, it was scarce, and its short action made it a test drug rather than a treatment. Its human results showed that blocking angiotensin-converting enzyme lowers blood pressure, and chemists used what they learned about how it fitted the enzyme to design captopril, the first oral ACE inhibitor, which made teprotide obsolete within a few years.
Mechanism of Action
Teprotide blocks angiotensin-converting enzyme, which both makes angiotensin II and breaks down bradykinin, so it lowers a pressure-raising hormone and can raise a pressure-lowering one.
Renin-dependent pressure fall
The larger the role of renin, the larger the fall: in high-renin patients it lowered peripheral resistance by about 30% (1980 haemodynamic study).
Bradykinin
Plasma kinins rose after it in some hypertensive patients but not in others, so how much bradykinin adds to its effect was never settled (1977 to 1981 human studies).
Template for captopril
Its fit to the enzyme guided the design of captopril, an oral drug with the same target (1982 account of captopril's design).
Published Research
Studies of teprotide (SQ 20881) itself, read from their PubMed abstracts: injections in people with hypertension, heart failure, renal artery disease and pre-eclampsia, studies in healthy volunteers, and laboratory and animal work on how it acts. Most are from 1977 to 1987, when it was used as a research and diagnostic tool.
Two ways of lowering pressure
In three groups of five patients, teprotide did nothing measurable in people with normal pressure and normal renin. In normal-renin hypertension mean arterial pressure fell 10%, mainly because the heart pumped less; in high-renin hypertension it fell 19% through a 30% drop in peripheral resistance, while cardiac output rose 13%. Heart rate did not rise in either group.
Stronger response in hypertension
In nine healthy people on a low-salt diet, 30 µg/kg of SQ 20881 lowered mean pressure by 5 mm Hg and raised kidney blood flow and renin. In six people with essential hypertension the threshold dose was a third as large, the same dose lowered pressure by 11 mm Hg, and plasma bradykinin rose only in this group.
Angiotensin II falls, kinins do not rise
Nine salt-replete hypertensive patients given 1 mg/kg intravenously had a pressure fall within 20 minutes, lowest at 60 minutes. Angiotensin II and aldosterone dropped and renin rose, while blood kinins fell slightly, so the authors put the effect down to less angiotensin II rather than more bradykinin.
Compared with captopril
On a 10 mEq sodium diet, 10 patients with normal-renin essential hypertension had a 13 mm Hg fall in diastolic pressure with teprotide, against 18 mm Hg in 21 patients on captopril, though renin and angiotensin II changed similarly. Plasma kinins rose with teprotide but not with captopril, pointing to different mechanisms.
Testing for renovascular hypertension
Twelve patients with renovascular hypertension had a fall in blood pressure and aldosterone and a rise in renin after an injection, and renin rose more in the vein of the affected kidney. All four patients with a positive test who had surgery became normotensive.
Kinins in renal hypertension
In eight patients with renal hypertension, 0.25 mg/kg intravenously lowered blood pressure and slowed the heart in five. Plasma kininase activity was inhibited, free kinins rose and kininogen fell; renin rose more in blood from the kidney with the narrowed artery.
Lower pressure in the lung circulation
In 13 patients who became hypertensive after coronary bypass surgery, teprotide cut pulmonary vascular resistance by 30% and mean pulmonary artery pressure by 23%, and right ventricular work fell by 30% while cardiac output rose. The changes tracked baseline renin, not changes in the left heart.
Heart failure: less work, same oxygen
In 11 patients with ischaemic heart disease and severe heart failure given captopril or teprotide, systemic resistance fell from about 2,400 to 1,700 units, cardiac output rose 18% and filling pressure fell. Coronary blood flow and oxygen use did not change, so the heart's efficiency improved without signs of ischaemia.
Reflexes kept in healthy volunteers
Teprotide lowered mean arterial pressure in healthy volunteers on high and low salt diets, but the normal rise in pressure with hand-grip exercise and the response to standing were preserved. Where fainting occurred after the injection, cardiac output had fallen as well as pressure.
No effect in post-partum pre-eclampsia
Five women with hypertension persisting after pre-eclamptic pregnancies received rising intravenous doses of 0.25 to 3.0 mg/kg about six hours after delivery. Before a diuretic it changed neither pressure nor renin; after furosemide, 1 mg/kg lowered pressure by 14% to 24% in three women, so the authors concluded the hypertension was not angiotensin-dependent.
Case: transplant patient with high renin
In a kidney transplant recipient with severe high-renin hypertension, intravenous and subcutaneous teprotide lowered pressure; the first fall came with a brief bradykinin rise, but the longer effect did not depend on it. A beta-blocker stopped the later rebound in renin and added to the effect.
Tight binding to the enzyme
Kinetic titration of the converting enzyme from bovine kidney cortex with SQ 20881, the venom nonapeptide, gave fast association and an equilibrium inhibition constant of about 2.5 nM, and the authors used it to count the enzyme's active sites.
Serum and brain enzyme differ
Converting-enzyme activity in human serum was more sensitive to captopril and teprotide than activity in homogenates of human caudate or mouse brain, whose inhibition curves were more complex, suggesting other enzymes or binding substances in brain tissue.
Bradykinin breakdown in artery walls
In perfused rat mesenteric beds, teprotide at 0.4 to 10 µmol/l, like captopril and enalaprilat, strongly potentiated bradykinin without stopping angiotensin I conversion, supporting the idea that long blood-pressure effects follow kininase inhibition in the artery wall.
More potent than captopril in dog vessels
In the mesenteric, renal and iliac circulations of dogs, SQ 20881 blocked angiotensin I conversion more potently than captopril and, unlike captopril, also increased the kidney's response to bradykinin.
Works only through angiotensin in rats
At 1 mg/kg, the most effective dose, teprotide lowered blood pressure in normal rats only after salt depletion, not after both kidneys were removed, and added nothing on top of the angiotensin antagonist saralasin.
Matched by a renin inhibitor in monkeys
In conscious salt-depleted monkeys, 1 mg/kg lowered mean pressure to a low point 13 minutes after injection, and the fall was similar to that from a peptide renin inhibitor, in both normotensive and acutely renal-hypertensive animals.
Less vessel growth in hypoxic rats
Rats injected with 2 mg/kg every 8 hours during a week of low oxygen had lower right ventricular pressure and less protein build-up in the pulmonary trunk than saline-treated hypoxic rats, though right ventricular enlargement was not prevented.
Ten weeks in rats
Rats given 3 mg/kg under the skin twice daily for up to 10 weeks showed no change in adrenal cortex structure or serum aldosterone, but renin granules in the kidney increased and the kidneys enlarged slightly.
Rabbits after bleeding
Pretreatment with 1.0 mg/kg blocked the blood-pressure and aldosterone response to a modest angiotensin I infusion in rabbits but not to a larger one, and it lowered pressure after haemorrhage but not in normal rabbits.
Dosing Data
Teprotide was never approved, so there is no label. These are the single intravenous doses given in the published human studies carded above, almost all as a one-off test of renin dependence.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
What a Buyer Needs to Know
What is sold, how it is mixed, stored and taken, and what is known about its safety, quality and legal status. Each part names its source. Where we have none, it says unknown.
What is sold
Unknown: we hold no label and no published test that says what forms or vial sizes Teprotide is sold in. A vial's own label is a seller's claim, not a source.
Mixing a vial: a worked example
No worked example: none of the doses on this page is a fixed amount in mg or mcg injected under the skin or into a muscle (the routes given are: intravenous). There is no home-mixing step to show. The reconstitution calculator does the arithmetic for any vial.
Source: the route and amount of each dose row in Dosing Data below.
Storage before and after mixing
Unknown: no label or published stability study on file says how to store Teprotide, before or after mixing. The mixing guide sets out the general rules, with their sources: keep a mixed vial in the fridge, and use it promptly, as the bacteriostatic water label says of any drug dissolved in it. The 28 days often quoted is the limit for an opened multiple-dose vial from a manufacturer, an outer limit set for sterility, not a time a mixed solution has been shown to keep. Nobody has published how long Teprotide stays intact once mixed.
How it is taken
As it was given in human studies: Intravenous (Single injection; Study: salt-replete hypertension, 9 patients).
For injection technique, sites and needle disposal, see the mixing guide.
Source: Used in human trials: the route and frequency of each row in Dosing Data below.
What to expect, and when
How long it stays in the body: not established by a measurement cited on this entry.
How long the doses were given: Study: salt-replete hypertension, 9 patients: Once, followed for 105 minutes; Study: renal hypertension, 8 patients: Once; Study: healthy volunteers and essential hypertension, low-salt diet: Once.
When effects appear: unknown; no source on this page gives a time to effect for Teprotide. Results reported in the studies are under Published Research.
Source: Used in human trials, the duration of each row in Dosing Data below.
Side effects, and when to stop or get help
From the Side Effects section: Fainting with a fall in blood pressure and cardiac output in some healthy volunteers (PMID 6185419); Large falls in blood pressure in renin-dependent patients, the effect the test was designed to show (PMID 6160013); A rebound rise in renin after the injection (PMID 6170971); No safety data beyond single injections and short animal courses. Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping Teprotide. Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“From the studies above, which were short and reported little on safety”).
Interactions
Unknown: a PubMed search for human interaction studies of Teprotide (reviewed 2026-10-28) found none. Unknown is not the same as safe to combine.
Every peptide's record, with its source: the interaction matrix.
Checking what you bought
Unknown: no published independent test of Teprotide products is in our lab-results database yet, so how products sold under this name measure up is not known.
To read a certificate of analysis, paste it into the COA decoder; it checks the measured mass against Teprotide's expected mass, 1,101.3 Da, from this entry's molecular data. Trust & Verification explains what independent testing can and cannot show.
Legal status
US: Research Chemical (Never approved). Sport: Prohibited (S0 catch-all).
Country by country ↓ · Regulatory tracker
Source: this entry's approval status and the WADA Prohibited List, as in Legal Status below.
Side Effects & Contraindications
Reported Side Effects
From the studies above, which were short and reported little on safety.
Contraindications & Cautions
No product label exists. These cautions follow from the evidence.
Legal Status
Teprotide was a research and diagnostic compound; it has never been approved as a medicine.
Frequently Asked Questions
?What is teprotide?
A nine-amino-acid peptide from the venom of the Brazilian pit viper Bothrops jararaca, made synthetically as SQ 20881. It blocks angiotensin-converting enzyme and was the first drug of that kind tested in people.
?How is it related to captopril?
Teprotide showed in people that blocking the converting enzyme lowers blood pressure, and its fit to the enzyme guided the design of captopril, an oral drug with the same target that replaced it.
?Why was teprotide never sold?
It worked only by injection, was scarce and acted briefly, so it was used as a test of renin-dependent hypertension rather than a treatment; captopril, taken by mouth, arrived soon after.
?What was it used for in patients?
Mostly as a single intravenous test: a large fall in blood pressure pointed to renin-driven hypertension, such as narrowing of a kidney artery, and helped choose surgery or drug treatment.
?Does it also affect bradykinin?
The same enzyme breaks down bradykinin, and some studies found kinins rose after teprotide, but others found they did not; its blood-pressure effect followed angiotensin II more closely.
References
- [other] PubChem CID 443376, Teprotide: formula C53H76N14O12, molecular weight 1101.3. Read October 28, 2026. https://pubchem.ncbi.nlm.nih.gov/compound/443376
- [clinical-trial] Niarchos AP, et al. "Hemodynamic effects of the converting enzyme inhibitor teprotide in normal- and high-renin hypertension." Clin Pharmacol Ther, 1980;28(5):592-601. PMID: 6160013.
- [clinical-trial] Williams GH, et al. "Accentuated vascular and endocrine response to SQ 20881 in hypertension." N Engl J Med, 1977;297(4):184-8. PMID: 195203.
- [clinical-trial] Hulthén L, et al. "The effect of the converting enzyme inhibitor SQ 20.881 on kinins, renin-angiotensin-aldosterone and catecholamines in relation to blood pressure in hypertensive patients." Acta Med Scand, 1978;204(6):497-502. PMID: 735881.
- [clinical-trial] Crantz FR, et al. "Differences in response to the peptidyldipeptide hydrolase inhibitors SQ 20,881 and SQ 14,225 in normal-renin essential hypertension." Hypertension, 1980;2(5):604-9. PMID: 6158478.
- [clinical-trial] Rosenthal T, et al. "Angiotensin-converting enzyme inhibitor (SQ 20881) in the diagnosis of renovascular hypertension." Angiology, 1979;30(2):123-8. PMID: 434566.
- [clinical-trial] Edery H, et al. "Blood kinin system in renal hypertensive patients administered with SQ 20881." Adv Exp Med Biol, 1979;120B:571-4. PMID: 517251.
- [clinical-trial] Niarchos AP, et al. "Effects of the converting enzyme inhibitor (SQ 20881) on the pulmonary circulation in man." Am J Med, 1979;67(5):785-91. PMID: 315711.
- [clinical-trial] Halperin JL, et al. "Coronary hemodynamic effects of angiotensin inhibition by captopril and teprotide in patients with congestive heart failure." Am J Cardiol, 1982;50(5):967-72. PMID: 6182786.
- [clinical-trial] Niarchos AP, et al. "Cardiovascular responses to isometric exercise and standing in normotensive subjects during converting enzyme inhibition with teprotide." Hypertension, 1982;4(4):538-44. PMID: 6185419.
- [clinical-trial] Sullivan JM, et al. "SQ 20,881: effect on eclamptic--pre-eclamptic women with postpartum hypertension." Am J Obstet Gynecol, 1978;131(7):707-15. PMID: 686062.
- [pubmed] VandenBurg MJ, et al. "Hormonal and blood pressure changes during converting enzyme inhibition by teprotide." Postgrad Med J, 1981;57(667):283-8. PMID: 6170971.
- [pubmed] Larionova NI, et al. "[Titration of active centers of enzymes by means of reversible inhibitors. Dipeptidyl-carboxypeptidase - inhibitor SQ 20881 from venom of the snake Bothrops jararca)]." Biokhimiia, 1982;47(8):1332-7. PMID: 6181819.
- [pubmed] Zubenko GS, et al. "Captopril and teprotide as discriminators of angiotensin-converting enzyme activity in brain tissue." Neurosci Lett, 1985;60(1):33-7. PMID: 2997673.
- [pubmed] Lindsey CJ, et al. "Effects of teprotide, captopril and enalaprilat on arterial wall kininase and angiotensin converting activity." J Hypertens Suppl, 1987;5(2):S71-6. PMID: 2821209.
- [pubmed] Fiksen-Olsen MJ, et al. "Effects of SQ 20881 and captopril on mesenteric, renal, and iliac vasculatures." Am J Physiol, 1983;244(3):H313-9. PMID: 6187226.
- [pubmed] Jaeger P, et al. "Mechanism of blood pressure reduction by teprotide (SQ 20881) in rats." Kidney Int, 1978;13(4):289-96. PMID: 651128.
- [pubmed] Takaori K, et al. "Hypotensive effects of the renin inhibitor (RI-78) and the converting enzyme inhibitor (teprotide) in conscious monkeys." Clin Exp Hypertens A, 1987;9(2-3):387-90. PMID: 3038400.
- [pubmed] McKenzie JC, et al. "Reduction in hypertension-induced protein synthesis in the rat pulmonary trunk after treatment with teprotide (SQ 20881)." Proc Soc Exp Biol Med, 1984;177(2):377-82. PMID: 6207542.
- [pubmed] Weaver J, et al. "Failure of chronic administration of the angiotensin I-converting enzyme inhibitor, Teprotide (SQ 20881), to affect the ultrastructure of the adrenal cortex and the aldosterone secretion in the rat." Lab Invest, 1981;45(6):527-33. PMID: 6172661.
- [pubmed] Saito I, et al. "Effects of converting enzyme inhibitor (SQ 20881) on changes in blood pressure and plasma aldosterone induced by angiotensin I or acute hemorrhage in rabbits." Jpn Heart J, 1980;21(1):95-101. PMID: 6154159.
- [review] Nemec K, et al. "[From teprotide to captopril. Rational design of ACE inhibitors]." Pharm Unserer Zeit, 2003;32(1):11-6. PMID: 12577755.
- [pubmed] Ruddy MC, et al. "Comparative effects of teprotide and captopril." Hypertension, 1981;3(2):277-8. PMID: 6163703.
- [review] Cushman DW, et al. "Development and design of specific inhibitors of angiotensin-converting enzyme." Am J Cardiol, 1982;49(6):1390-4. PMID: 6176105.
- [pubmed] Tifft CP, et al. "Converting enzyme inhibition in hypertensive emergencies." Ann Intern Med, 1979;90(1):43-7. PMID: 420460.
- [review] DiBianco R, et al. "Adverse reactions with angiotensin converting enzyme (ACE) inhibitors." Med Toxicol, 1986;1(2):122-41. PMID: 3023783.
Sources & Citations
Every study on this page was read from its PubMed record on October 28-29, 2026. Regulatory status comes from Drugs@FDA (openFDA) and the EMA medicines list, read October 28, 2026; the formula and weight are PubChem's. Grey Peptides sells nothing and links to no vendor.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.