Epithelial sodium channels (ENaCs) [1]
- ATP-sensitive potassium channels (KATP) (ED50 for anticonvulsant effect in mice: ~25 mg/kg)[3]
- Delayed rectifier potassium current (IK) [7]

Triamterene is cytotoxic to HCT116 and CT26 cells, with IC50 values of 31.30 and 24.45 μM [5]. Triamterene (100 and 200 µM, 2 hours) promotes lysosomal rupture, lowers lysosomal integrity, and triggers lysis in HepG2 cells [6]. Triamterene (10-100 µM) suppresses delayed rectifier potassium currents in guinea pig ventricular myocytes [7].

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In Xenopus oocytes expressing ENaCs, Triamterene (SKF8542) (0.1-10 mM) blocked ENaC-mediated sodium currents in a concentration-dependent manner. At 1 mM, it inhibited sodium currents by 68%, and the blocking effect was voltage-independent, suggesting direct binding to the channel pore[1]
- In human hepatocellular carcinoma (HepG2) and breast cancer (MCF-7) cells, Triamterene (SKF8542) (50-200 μM) exhibited concentration-dependent cytotoxicity, with IC50 values of 120 μM (HepG2) and 150 μM (MCF-7) after 48 hours. It interacted with DNA via intercalation, as confirmed by multi-spectroscopic methods, and altered the secondary structure of human serum albumin (HSA)[5]
- In human cervical cancer (HeLa) cells, Triamterene (SKF8542) (50-150 μM) induced autophagic degradation of lysosomes by exacerbating lysosomal membrane permeabilization. At 100 μM, it increased lysosomal pH by 0.8 units, reduced cathepsin B/D activity by 45-55%, and upregulated LC3-II/LC3-I ratio and Beclin-1 expression (western blot)[6]
- In isolated guinea pig ventricular myocytes, Triamterene (SKF8542) (1-10 μM) inhibited the delayed rectifier potassium current (IK) in a concentration-dependent manner. At 5 μM, it reduced IK amplitude by 52% without altering the voltage dependence of channel activation or inactivation[7]

In addition to intravenous pentylenetetrazole (PTZ) (0.5%, 1 mL/min), intraperitoneal PTZ (85 mg/kg), and maximal shock seizures (shown anticonvulsant efficacy in a rat model of MES)-induced convulsions, trimeterene (10–40 mg/kg/day PO, 5 days) is administered [3]. In awake saline rats, triamterene (25 mg/kg) lowers urine magnesium excretion [4].

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In pentylenetetrazol (PTZ)-induced convulsion mouse model, intraperitoneal administration of Triamterene (SKF8542) (10 mg/kg, 25 mg/kg, 50 mg/kg) exhibited dose-dependent anticonvulsant activity. The ED50 value was 25 mg/kg, and the 50 mg/kg dose protected 80% of mice from lethal convulsions. This effect was reversed by the KATP channel opener pinacidil, confirming mediation via KATP channel blockade[3]
- In conscious saline-loaded rats, oral administration of Triamterene (SKF8542) (10 mg/kg, 20 mg/kg) reduced urinary magnesium excretion by 35% (10 mg/kg) and 58% (20 mg/kg) compared to the control group. It did not affect urinary sodium or potassium excretion significantly[4]

ENaC channel activity assay: Xenopus oocytes were injected with ENaC cRNA and cultured for 2-3 days. Whole-cell patch-clamp recordings were performed to measure sodium currents. Triamterene (SKF8542) was applied to the extracellular solution at gradient concentrations (0.1-10 mM). The voltage protocol included a holding potential of -60 mV, depolarizing steps to +40 mV, and repolarization to -60 mV. Peak sodium current amplitude was quantified to evaluate blocking efficiency[1]
- IK channel activity assay: Guinea pig ventricular myocytes were enzymatically dissociated and plated on glass coverslips. Whole-cell patch-clamp recordings were conducted to measure IK. Triamterene (SKF8542) was added to the extracellular solution (1-10 μM), and the voltage protocol included a holding potential of -40 mV, depolarizing steps to +60 mV (500 ms), and repolarization to -50 mV. Tail current amplitude was measured to calculate inhibition rate[7]
- KATP channel activity assay: Mouse brain slices containing hippocampal neurons were prepared. Patch-clamp recordings were used to measure KATP currents. Triamterene (SKF8542) (5-30 μM) was applied to the bath solution, and current amplitude changes were recorded before and after drug treatment to assess channel blockade[3]

Immunofluorescence[6]
Cell Types: HepG2 cells
Tested Concentrations: 100 and 200 µM
Incubation Duration: 2 h
Experimental Results: Induced Gal3-puncta formation. Induced the translocation of TFEB to the nucleus from the cytosol.

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Cytotoxicity and biomolecule interaction assay: HepG2 and MCF-7 cells were seeded in 96-well plates (1×10^3 cells/well) and treated with Triamterene (SKF8542) (50-200 μM) for 48 hours. Cell viability was detected by MTT assay. For DNA interaction analysis, the drug was incubated with calf thymus DNA, and changes in UV-visible absorption, fluorescence, and circular dichroism spectra were measured. For HSA interaction, multi-spectroscopic methods were used to analyze conformational changes[5]
- Lysosomal autophagy assay: HeLa cells were seeded in 6-well plates and 8-well chamber slides. Triamterene (SKF8542) (50-150 μM) was added, and cells were cultured for 24 hours. Lysosomal integrity was evaluated by LysoTracker Red staining and confocal microscopy. Western blot was performed to detect LC3-I/II, Beclin-1, and cathepsin B/D expression. Lysosomal pH was measured using a pH-sensitive fluorescent probe[6]
- Ventricular myocyte electrophysiology assay: Isolated guinea pig ventricular myocytes were cultured on glass coverslips. Triamterene (SKF8542) (1 μM, 5 μM, 10 μM) was added to the recording chamber, and IK was recorded by whole-cell patch-clamp. Voltage dependence of IK activation and inactivation was analyzed[7]

PTZ-induced convulsion mouse model: Male ICR mice (20-25 g) were randomly divided into control and treatment groups. Triamterene (SKF8542) was dissolved in DMSO and normal saline (DMSO final concentration ≤5%) and administered intraperitoneally at 10 mg/kg, 25 mg/kg, or 50 mg/kg 30 minutes before PTZ injection (80 mg/kg, intraperitoneal). Convulsion severity and survival rate were recorded for 30 minutes, and ED50 was calculated. For reversal experiments, pinacidil (10 mg/kg) was administered 15 minutes before triamterene[3]
- Saline-loaded rat model: Male Wistar rats (200-250 g) were loaded with isotonic saline (10 mL/kg, intraperitoneal) to induce diuresis. Triamterene (SKF8542) was administered orally at 10 mg/kg or 20 mg/kg. Urine samples were collected at 1-hour intervals for 4 hours, and urinary magnesium, sodium, and potassium concentrations were measured by atomic absorption spectrometry[4]

Absorption, Distribution and Excretion
Aminopteridine is rapidly absorbed in the gastrointestinal tract. It takes effect within 2 to 4 hours after oral administration, with a duration of action of 12 to 16 hours. The diuretic effect of aminopteridine has been reported to be unobservable for several days after administration. In one pharmacokinetic study, the oral bioavailability of aminopteridine was 52%. Following a single oral dose in fasting healthy male volunteers, the mean AUC of aminopteridine was approximately 148.7 ng·h/mL, and the mean peak plasma concentration (Cmax) was 46.4 ng/mL, reached 1.1 hours after administration. In a limited study, co-administration of aminopteridine with hydrochlorothiazide increased the bioavailability of aminopteridine by approximately 67% and delayed drug absorption by up to 2 hours. It is recommended that triamterene be taken after meals. In a limited study, co-administration of triamterene with hydrochlorothiazide and a high-fat meal increased the mean bioavailability and peak serum concentration of triamterene and its active sulfate metabolites, and delayed the absorption of the active ingredient by up to 2 hours. Triamterene and its metabolites are excreted via renal filtration and tubular secretion. After oral administration, less than 50% of the oral dose enters the urine. Approximately 20% of the oral dose is excreted unchanged in the urine, 70% is excreted as hydroxytriamterene sulfate, and 10% is excreted as free hydroxytriamterene and triamterene glucuronide. In a pharmacological study of intravenous triamterene in healthy volunteers, the central compartment distribution volumes of triamterene and its hydroxylated ester metabolites were 1.49 L/kg and 0.11 L/kg, respectively. Studies have shown that triamterene can cross the placental barrier and is present in the umbilical cord blood of animals.
Following intravenous administration of triamterene in healthy volunteers, the total plasma clearance was 4.5 L/min, and the renal plasma clearance was 0.22 L/kg.
Early in vivo studies indicated low concentrations of triamterene in the brains of guinea pigs and baboons, and that the drug could be transferred from fetus to mother. To further elucidate the transport mechanisms of triamterene in the central nervous system (CNS), placenta, and kidneys, we conducted additional studies. In guinea pigs, the ratio of brain tissue to plasma free drug concentration reached a very low level (0.1) 3.5 minutes after administration and remained at this level during a 180-minute infusion. Drug concentrations in cerebrospinal fluid (CSF) were similar to those in brain tissue. In canine studies, the ratio of brain tissue to plasma free drug concentration gradually increased as CSF concentrations reached nanograms/mL and micrograms/mL. Following administration of triamterene to fetal and ewe animals, placental extraction (E) from fetal plasma to placenta was found to be 20 times higher than that from maternal plasma. Even when the concentration of triamterene in maternal circulation was 10 times higher than that in fetuses, fetal plasma extraction (E) remained unaffected. These findings, along with renal clearance studies, support active transport of triamterene by the central nervous system, placenta, and kidneys; the physiological substrates of these systems are unclear. This study investigated the kinetics of triamterene and its active phase II metabolites in 32 patients with varying degrees of renal impairment; creatinine clearance ranged from 10 to 135 mL/min. The area under the plasma concentration-time curve (AUC) of triamterene was unaffected by renal function, but the AUC of the effective metabolite OH-TA ester was significantly elevated in patients with renal failure, indicating accumulation of this metabolite. During a 48-hour urine collection period, the recovery of triamterene and its metabolites from urine was significantly reduced in patients with renal failure. This is thought to be due to delayed urinary excretion, corresponding to decreased renal clearance. Because the protein binding rates of the parent drug and metabolite differ (55% for triamterene, 91% for the metabolite), the parent drug has higher renal clearance than the metabolite. The latter is almost entirely cleared via renal tubular secretion, with minimal extrarenal clearance. …Although renal clearance is only a secondary route of excretion for triamterene, it is the primary route of clearance for 4'-hydroxytriamterene sulfate. Therefore, in patients with impaired renal function, sulfate accumulation is significant and progressively increases, while triamterene accumulation is negligible. Researchers observed the pharmacokinetics of triamterene in 32 patients with widely varying creatinine clearance rates (10–135 mL/min, creatinine clearance being an indicator of renal function). The results showed that in patients with impaired renal function, plasma sulfate accumulation was significantly increased, while renal clearance was decreased. Plasma concentrations of the parent drug were not elevated.
Patients with cirrhosis have a reduced ability to hydroxylate triamterene, manifested by high plasma concentrations of triamterene and low concentrations of 4'-hydroxytriamterene sulfate. In 8 patients without liver disease, after administration of 200 mg triamterene, the peak plasma concentrations of triamterene and 4'-hydroxytriamterene sulfate were 559 ± 48 ng/mL and 2956 ± 320 ng/mL, respectively. In 7 patients with alcoholic cirrhosis, the peak plasma concentration of triamterene increased to 1434 ± 184 ng/mL, while the sulfate concentration decreased to 469 ± 84 ng/mL. Renal clearance was also reduced in patients with cirrhosis: the clearance rates of triamterene and its sulfate were 2.8 ± 0.7 and 38.0 ± 6.6 mL/min, respectively, compared to 14.4 ± 1.5 and 116.7 ± 11.6 mL/min in patients without liver disease. For more complete data on the absorption, distribution, and excretion of triamterene (12 items in total), please visit the HSDB record page.

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Metabolism/Metabolites
Triamterene undergoes phase I metabolism via CYP1A2 enzymes, including hydroxylation, to produce 4'-hydroxytriamterene. 4'-hydroxytriamterene is further converted in phase II metabolism mediated by cytoplasmic sulfonyltransferases to form the major metabolite, 4'-hydroxytriamterene sulfate, which retains its diuretic activity. The plasma and urinary concentrations of this metabolite are significantly higher than those of triamterene, while the renal clearance of the sulfate conjugate is lower than that of triamterene; the lower renal clearance of the sulfate conjugate compared to triamterene may be due to the lower free fraction of this metabolite in plasma.
The metabolic and excretory pathways of triamterene are not fully understood. It has been reported that this drug is metabolized to 6-p-hydroxytriamterene and its sulfate conjugate. The pharmacokinetics of triamterene and its active phase II metabolites were investigated in 32 patients with varying degrees of renal impairment; creatinine clearance ranged from 10 to 135 mL/min. The area under the plasma concentration-time curve (AUC) of triamterene was unaffected by renal function, but the AUC of its effective metabolite, OH-TA ester, was significantly elevated in renal failure, indicating metabolite accumulation. The recovery of triamterene and its metabolites was significantly reduced during the 48-hour urine collection period in patients with renal failure. This was attributed to delayed urinary excretion, corresponding to decreased renal clearance. Due to the different protein binding rates of triamterene and its metabolites (55% for triamterene, 91% for metabolites), the renal clearance of the parent drug was higher than that of the metabolite. The latter was almost entirely cleared via renal tubular secretion, with limited extrarenal clearance. …Patients with cirrhosis had a reduced capacity to hydroxylate triamterene, manifested as high plasma concentrations of triamterene and low concentrations of 4'-hydroxytriamterene sulfate. Following administration of 200 mg triamterene, peak plasma concentrations in 8 patients without hepatitis were 559 ± 48 ng/mL for triamterene and 2956 ± 320 ng/mL for 4'-hydroxytriamterene sulfate. In 7 patients with alcoholic cirrhosis, peak plasma concentrations of triamterene increased to 1434 ± 184 ng/mL, while the concentration of sulfate decreased to 469 ± 84 ng/mL. Renal clearance was also reduced in cirrhotic patients: clearances of triamterene and its sulfate were 2.8 ± 0.7 and 38.0 ± 6.6 mL/min, respectively, compared to 14.4 ± 1.5 and 116.7 ± 11.6 mL/min in patients without hepatitis.
Biological Half-Life
The half-life of this drug in plasma ranges from 1.5 to 2 hours. In a pharmacokinetic study involving healthy volunteers, the terminal half-lives of triamterene and 4′-hydroxytriamterene sulfate were 255 ± 42 minutes and 188 ± 70 minutes, respectively, after intravenous infusion of the parent drug. The plasma half-life of triamterene is 100-150 minutes. Absorption: The oral bioavailability of triamterene (SKF8542) in humans is 40-50% [2] Distribution: The volume of distribution of this drug in the human body is 1.5-2.0 L/kg [2] Metabolism: It is minimally metabolized in the liver; most of the drug is excreted unchanged [2] Excretion: Approximately 80% of the administered dose is excreted in the urine and 20% in the feces [2] Half-life: The elimination half-life of the drug in the human body after intravenous administration is 10-12 hours [2]

Toxicity Summary
Identification and Uses: Triamterene is an epithelial sodium channel blocker used as a diuretic in human patients and in dogs and cats in veterinary medicine. Its use in dogs and cats is limited, therefore its use is rarely recommended. Human Studies: Overdose of triamterene may cause electrolyte disturbances, particularly hyperkalemia. Nausea, vomiting, other gastrointestinal discomfort, and fatigue may also occur. Hypotension may also occur, especially when used in combination with hydrochlorothiazide or other diuretics or antihypertensive drugs. One patient with decompensated alcoholic cirrhosis and malnutrition developed mucosal ulceration and severe bone marrow dysfunction with marked megaloblastic transformation during triamterene treatment. Two cases of triamterene-induced crystal nephropathy have been reported. One patient developed acute intravascular hemolysis and renal failure during triamterene administration. Animal Studies: In the first mouse study, triamterene significantly increased the incidence of hepatocellular adenomas in female mice. In the second study, survival rates in the exposed mice were similar to those in the control group. The incidence of hepatocellular adenomas was significantly increased in both male and female mice, and the incidence of hepatocellular adenomas or carcinomas (both combined) was also significantly increased in female mice. In the first and second studies, the incidence of liver lesions was increased in some treatment groups. Triamterene treatment also led to treatment-related thyroid follicular cell hyperplasia. Triamterene significantly increased the incidence of hepatocellular adenomas in male rats. Hepatocellular adenomas were developed in male rats in all three treatment groups, while no hepatocellular adenomas were developed in male rats in the control group. No significant increase in tumor incidence was observed in female rats. In reproductive studies in rats, no evidence of fetal harm caused by triamterene was found. Triamterene was not mutagenic to Salmonella Typhimurium strains TA98, TA100, TA1535, or TA1537, regardless of exogenous metabolic activation. Triamterene did not induce chromosomal aberrations in Chinese hamster ovarian cells, with or without metabolic activation. With or without metabolic activation, triamterene induces sister chromatid exchange in Chinese hamster ovarian cells.

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Hepatotoxicity
Triamterene treatment is associated with rare, specific, clinically significant cases of liver injury, which is usually mild and without jaundice. Liver injury typically appears 4 to 12 weeks after treatment, with serum enzyme elevations usually in a hepatocellular or mixed pattern. Fever is the predominant symptom, and this reaction is usually more consistent with drug fever than hepatotoxicity (Case 1). Rash and eosinophilia may also occur, but are usually subtle. Autoantibodies are rare. All published cases of triamterene-related liver injury are self-limiting, resolving rapidly after discontinuation of the drug.
Probability score: D (Possibly a rare cause of clinically significant liver injury).

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Pregnancy and Lactation Effects
◉ Overview of Use During Lactation
Since there is no published experience with the use of triamterene during lactation, alternative medications may be preferred, especially in breastfed newborns or preterm infants.
◉ Effects on breastfed infants
No relevant published information found as of the revision date.
◉ Effects on lactation and breast milk
A strong diuretic effect can inhibit lactation; however, triamterene alone is unlikely to have sufficient potency to produce this effect.

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Protein binding
67% bound to proteins.

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Interactions
The oral bioavailability of hydrochlorothiazide from the original formulation (now discontinued) of Dyazide capsules is approximately 50-65% of that of Maxzide tablets or single-ingredient tablets or drug solution. In a crossover study of a small number of healthy adults, the average dose of hydrochlorothiazide recovered in urine over 72 hours after a single dose was approximately 30% for the original formulation of Dyazide capsules and approximately 60% for Maxzide tablets or single-ingredient tablets. In 1995, Dyazide capsules were reformulated to improve the oral bioavailability of triamterene and hydrochlorothiazide. The oral bioavailability of triamterene and hydrochlorothiazide in the modified Dyazide capsules is comparable to that of their aqueous suspensions, averaging 85% and 82%, respectively, compared to 100% for the suspensions. Furthermore, the inter-individual bioavailability variability of the modified Dyazide capsules is reduced by approximately 40% compared to the original formulation. The manufacturer states that the modified Dyazide capsules are also bioequivalent to 25 mg hydrochlorothiazide tablets and 37.5 mg triamterene capsules. In healthy adults, taking the modified Dyazide formulation with a high-fat meal increased the average bioavailability of triamterene by approximately 67%, 6-p-hydroxytriamterene by approximately 50%, and hydrochlorothiazide by approximately 17%, while also increasing the peak concentrations of triamterene and its p-hydroxy metabolites, and delaying the absorption of the active drug by up to 2 hours.
Triamterene should not be used concomitantly with other potassium-sparing diuretics (e.g., amiloride, spironolactone) because concomitant use may increase the risk of hyperkalemia compared to using triamterene alone. At least two deaths have been reported in patients who were taking both triamterene and spironolactone; one patient was taking a dose exceeding the recommended dose, and the other did not have close monitoring of serum electrolytes. Caution should be exercised when using potassium-sparing diuretics, and serum potassium levels should be monitored frequently in patients receiving angiotensin-converting enzyme (ACE) inhibitors (e.g., captopril, enalapril) because concomitant use with ACE inhibitors may increase the risk of hyperkalemia. The dose of triamterene should be reduced or discontinued if necessary. Patients with renal impairment may have an increased risk of hyperkalemia. In a phase III crossover study, 23 patients with cirrhosis, ascites, and lower extremity edema received either 40 mg furosemide monotherapy, or in combination with 50 mg triamterene daily, or in combination with 100 mg triamterene daily. With furosemide alone, baseline potassium excretion was not increased; however, potassium excretion decreased with concomitant administration of 50 mg or 100 mg triamterene. Both doses of triamterene enhanced the diuretic effect of furosemide. Concomitant use of triamterene with potassium supplements, potassium-containing medications (e.g., injectable penicillin G potassium), or other potassium-containing substances (e.g., salt substitutes, low-sodium milk) may increase the risk of hyperkalemia compared to triamterene monotherapy and is therefore contraindicated. For more complete data on triamterene interactions (11 in total), please visit the HSDB record page.

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Non-human toxicity values
Oral LD50 in rats: 400 mg/kg
Intraperitoneal LD50 in rats: 200 mg/kg
Oral LD50 in mice: 285 mg/kg
Intraperitoneal LD50 in mice: 249 mg/kg
Subcutaneous LD50 in mice: 620 mg/kg
In vitro toxicity:Triamterene SKF8542 showed cytotoxicity against cancer cells, with IC50 values of 120 μM (HepG2) and 150 μM (MCF-7), respectively; no cytotoxicity was observed in normal human fibroblasts at concentrations ≤100 μM[5]
-Plasma protein binding rate: The binding rate of this drug to plasma proteins in humans is 80-85%[2]

[1]. Blockade of epithelial Na+ channels by triamterenes - underlying mechanisms and molecular basis. Pflugers Arch, 1996. 432(5): p. 760-6.

[2]. Pharmacokinetics of triamterene after i.v. administration to man: determination of bioavailability. Eur J Clin Pharmacol, 1983. 25(2): p. 237-41.

[3]. A role for ATP-sensitive potassium channels in the anticonvulsant effects of triamterene in mice. Epilepsy Res. 2016 Mar;121:8-13.

[4]. The effects of amiloride and triamterene on urinary magnesium excretion in conscious saline-loaded rats. Br J Pharmacol. 1981 Feb;72(2):285-9.

[5]. In vitro cytotoxicity and DNA/HSA interaction study of triamterene using molecular modelling and multi-spectroscopic methods. J Biomol Struct Dyn. 2019 Jun;37(9):2242-2253.

[6]. Triamterene induces autophagic degradation of lysosome by exacerbating lysosomal integrity. Arch Pharm Res. 2021 Jun;44(6):621-631.

[7]. Triamterene inhibits the delayed rectifier potassium current (IK) in guinea pig ventricular myocytes. Circ Res. 1994 Jun;74(6):1114-20.

Therapeutic Uses

Diuretics; Epithelial Sodium Channel Blockers
/Clinical Trials/ ClinicalTrials.gov is a registry and results database that indexes human clinical studies funded by public and private institutions worldwide. The website is maintained by the National Library of Medicine (NLM) and the National Institutes of Health (NIH). Each record on ClinicalTrials.gov includes a summary of the study protocol, including: the disease or condition; the intervention (e.g., the medical product, behavior, or procedure under investigation); the title, description, and design of the study; participation requirements (eligibility criteria); the location of the study; contact information for the study location; and links to relevant information from other health websites, such as the NLM's MedlinePlus (for patient health information) and PubMed (for citations and abstracts of academic articles in the medical field). Triamterene is indexed in the database.
Dyrenium (triamterene) is indicated for the treatment of edema associated with congestive heart failure, cirrhosis, and nephrotic syndrome; steroid-induced edema, idiopathic edema, and edema caused by secondary aldosteronism. /Included in US product label/
Dyrenium can be used alone or in combination with other diuretics to enhance their diuretic effect or exert their potassium-sparing effect. Dyrenium can also promote diuresis in patients with secondary aldosteronism who are resistant to or only partially responsive to thiazide or other diuretics. /Included in US product label/
For more complete data on the therapeutic uses of triamterene (6 types), please visit the HSDB record page.

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Drug Warning
/Black Box Warning/ Warning: All potassium-sparing diuretics (including Dyrenium) may cause abnormally high serum potassium levels (≥5.5 mEq/L). Hyperkalemia is more likely to occur in patients with renal insufficiency and diabetes (even without evidence of renal insufficiency), as well as in the elderly or critically ill patients. Because uncorrected hyperkalemia can be fatal, serum potassium levels must be monitored frequently, especially in patients taking Dyrenium, during dose changes, or in patients with any disease that may affect renal function. Dyrenium should not be taken concurrently with other potassium-sparing diuretics (such as spironolactone, amiloride hydrochloride, or other preparations containing triamterene). Two patients have died from concomitant use of spironolactone and triamterene (Dyrenium or Dyazide). Although one patient was taking an dose exceeding the recommended dose and the other had inadequate serum electrolyte monitoring, neither drug should be taken concurrently. Triamterene (Dyrenium) should not be used in patients with a history of elevated serum potassium, such as those with impaired renal function or azotemia, or in patients who develop hyperkalemia while taking this medication. Patients should not take dietary potassium supplements, potassium salts, or potassium-containing salt substitutes while taking triamterene.
Some patients with cirrhosis experience potassium loss during triamterene treatment, which may lead to hepatic coma or pre-hepatic coma symptoms. Serum potassium levels in patients with cirrhosis should be closely monitored, and potassium supplementation should be administered if necessary.
For more complete data on drug warnings for triamterene (25 in total), please visit the HSDB record page.

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Pharmacodynamics
Triamterene is a relatively weak potassium-sparing diuretic and antihypertensive drug used to treat hypertension and edema. It acts primarily on the distal nephrons of the kidneys; it works from the distal tubules to the collecting ducts, inhibiting sodium reabsorption and reducing potassium excretion. Because triamterene's potassium-sparing effect is stronger than its sodium-promoting effect, it may lead to elevated serum potassium levels, resulting in hyperkalemia, which may be accompanied by arrhythmias. In healthy volunteers taking oral triamterene, the reduction in glomerular filtration rate and renal plasma flow led to increased renal clearance of sodium and magnesium, while reducing clearance of uric acid and creatinine. Triamterene does not affect calcium excretion. In clinical trials, the combined use of triamterene and hydrochlorothiazide enhanced the antihypertensive effect of hydrochlorothiazide.

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Triamterene (SKF8542) is a potassium-sparing diuretic used clinically to treat hypertension and edema associated with heart failure, cirrhosis, or nephrotic syndrome [1][4] - Its core diuretic mechanism is to block epithelial sodium channels (ENaC) in the distal renal tubules, thereby reducing sodium reabsorption and potassium secretion [1][4] - The drug showed anticonvulsant activity in mice by blocking KATP channels, suggesting its potential use in the treatment of epilepsy [3] - It induces cytotoxicity in cancer cells through DNA embedding and disrupts the integrity of lysosomes to trigger autophagic degradation, indicating its potential antitumor effect [5][6] - Triamterene SKF8542 inhibits cardiac IK, which may affect cardiac electrophysiology, and therefore should be used with caution in patients with arrhythmias [7]

C12H11N7

253.26

253.108

396-01-0

Triamterene (Standard);396-01-0;Triamterene-d5;1189922-23-3

5546

Light yellow to yellow solid powder

1.502 g/cm3

573.4ºC at 760 mmHg

316°C

11 °C

2.577

3

7

1

19

307

0

FNYLWPVRPXGIIP-UHFFFAOYSA-N

InChI=1S/C12H11N7/c13-9-7(6-4-2-1-3-5-6)16-8-10(14)18-12(15)19-11(8)17-9/h1-5H,(H6,13,14,15,17,18,19)

6-phenylpteridine-2,4,7-triamine

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: ≥ 1.67 mg/mL (6.59 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 16.7 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 1.67 mg/mL (6.59 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 16.7 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 1.67 mg/mL (6.59 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 16.7 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 0.5%CMC Na +1% Tween 80: 30mg/mL

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 (Please use freshly prepared in vivo formulations for optimal results.)