Triamterene Chemical Properties

Melting point:

316°C

Boiling point:

386.46°C (rough estimate)

Density 

1.3215 (rough estimate)

refractive index 

1.8260 (estimate)

Flash point:

11 °C

storage temp. 

2-8°C

solubility 

formic acid: soluble200 mg + 4 mL warm Formic Acid, clear, yellow-green

pka

6.2(at 25℃)

color 

Pale Yellow to Yellow

Water Solubility 

<0.1 G/100 ML AT 20 ºC

Merck 

14,9599

BRN 

266723

InChIKey

FNYLWPVRPXGIIP-UHFFFAOYSA-N

CAS DataBase Reference

396-01-0(CAS DataBase Reference)

NIST Chemistry Reference

Triamterene(396-01-0)

IARC

2B (Vol. 108) 2016

EPA Substance Registry System

Triamterene (396-01-0)

Safety Information

Hazard Codes 

Xn,T,F

Risk Statements 

22-36/37/38-36/38-23/25-39/23/24/25-23/24/25-11

Safety Statements 

26-36/37/39-45-33-24-16-7-36/37

RIDADR 

2811

WGK Germany 

3

RTECS 

UO3470000

HazardClass 

6.1(b)

PackingGroup 

III

HS Code 

2933997500

Hazardous Substances Data

396-01-0(Hazardous Substances Data)

MSDS

• Language:English Provider:2,4,7-Triamino-6-phenylpteridine
• Language:English Provider:SigmaAldrich
• Language:English Provider:ALFA

Triamterene Usage And Synthesis

Description

Triamterene is an inhibitor of the epithelial sodium channel (ENaC; IC₅₀ = 4.5 μM for the rat channel). In vivo, triamterene (0.5-32 mg/animal) enhances sodium secretion and decreases potassium secretion in adrenalectomized rats. Formulations containing triamterene have been used in the treatment of edema. This product is also available as an analytical reference standard .

Chemical Properties

Yellow Solid

Originator

Jatropur,Rohm,W. Germany,1962

Uses

Triamterene is a potassium-sparing diuretic ie, it inhibits the urinary excretion of potassium

Uses

This drug is recommended in combination with other diuretics for treating edema caused by usual reasons such as circulatory insufficiency, cirrhosis of the liver, and nephrotic syndrome.

Uses

Triamterene is a weak diuretic with potassium sparing properties; blocks Na+ reuptake in the kidneys.

Definition

ChEBI: Triamterene is pteridine substituted at positions 2, 4 and 7 with amino groups and at position 6 with a phenyl group. A sodium channel blocker, it is used as a diuretic in the treatment of hypertension and oedema. It has a role as a diuretic and a sodium channel blocker.

Manufacturing Process

To a solution of 9 grams of 5-nitroso-2,4,6-triaminopyrimidine in 500 mi of refluxing dimethylformamide is added 9 grams of phenylacetonitrile and the refluxing is stopped. The 3 grams of anhydrous sodium methoxide is added and the mixture is refluxed for 15 minutes. The mixture is chilled and the solid is filtered and washed several times with warm water until the washings are neutral. Drying gives yellow crystals which are recrystallized with a Darco treatment from formamide-water heating the solution no hotter than 125°C.
This product is then suspended in filtered deionized water and warmed for 15 minutes. This yields the 2,4,7-triamino-6-phenylpteridine as yellow crystals with a MP of 314° to 317°C.

Therapeutic Function

Diuretic

Biological Functions

Triamterene (Dyrenium) results in changes in urinary electrolyte patterns that are qualitatively similar to those produced by spironolactone. The mechanism by which this agents bring about the alterations in electrolyte loss, however, is quite different. Triamterene produces this effects whether or not aldosterone or any other mineralocorticoid is present. The action of this drug is clearly unrelated to endogenous mineralocorticoid activity, and this drug is effective in adrenalectomized patients.

General Description

Odorless yellow powder or crystalline solid. Melting point 316°C. Almost tasteless at first and with a slightly bitter aftertaste. Acidified solutions give a blue fluorescence. Used as a diuretic drug.

Air & Water Reactions

Sensitive to light; slowly oxidized upon exposure to air. Insoluble in water.

Reactivity Profile

2,4,7-Triamino-6-phenylpteridine neutralizes acids in exothermic reactions to form salts plus water. May be incompatible with isocyanates, halogenated organics, peroxides, phenols (acidic), epoxides, anhydrides, and acid halides. Flammable gaseous hydrogen may be generated in combination with strong reducing agents, such as hydrides.

Fire Hazard

Flash point data for 2,4,7-Triamino-6-phenylpteridine are not available; however, 2,4,7-Triamino-6-phenylpteridine is probably combustible.

Mechanism of action

Triamterene is a pyrazine derivative that inhibits reabsorption of sodium ions without increasing excretion of potassium ions. It exhibits the same approximate effect as spironolactone; however, it does not competitively bind with aldosterone receptors. Its action does not have an effect on secretion of aldosterone or its antagonists, which are a result of direct action on renal tubules.
This potassium sparing diuretic causes a moderate increase in excretion of sodium and bicarbonate ions in urine, and it raises excretion of potassium and ammonia ions. It has little effect on urine volume.

Clinical Use

Triamterene can be used in the treatment of congestive heart failure, cirrhosis, and the edema caused by secondary hyperaldosteronism. It is frequently used in combination with other diuretics except spironolactone. Amiloride, but not triamterene, possesses antihypertensive effects that can add to those of the thiazides. These K⁺-sparing diuretics have low efficacy when used alone, since only a small amount of total Na reabsorption occurs at more distal sites of the nephron.
These compounds are used primarily in combination with other diuretics, such as the thiazides and loop diuretics, to prevent or correct hypokalemia. The availability of fixed-dose mixtures of thiazides with nonsteroidal K⁺-sparing compounds has proved a rational form of drug therapy. Both triamterene and amiloride are available alone or in combination with hydrochlorothiazide.

Side effects

Because the actions of triamterene and amiloride are independent of plasma aldosterone levels, their prolonged administration is likely to result in hyperkalemia. Both amiloride and triamterene are contraindicated in patients with hyperkalemia.Triamterene should not be given to patients with impaired renal function. Potassium intake must be reduced, especially in outpatients.A folic acid deficiency has been reported to occur occasionally following the use of triamterene.

Synthesis

Triamterene, 2,4,7-triamino-6-phenylpteridine (21.5.13), is synthesized in by the following scheme. Reacting guanidine with malonodinitrile gives 2,4,6-triaminopyrimidine (21.5.11). This undergoes nitrosation by reacting it with nitric acid, which results in the formation of 5-nitroso-2,4,6-triaminopyrimidine (21.5.12), which upon condensation with benzyl cyanide in the presence of sodium methoxide cyclizes into triamterene (21.5.13).

Veterinary Drugs and Treatments

Triamterene is a potassium-sparing diuretic that potentially could be used as an alternative to spironolactone for the adjunctive treatment of congestive heart failure in dogs, however, there is little experience associated with its use in dogs or cats.

Drug interactions

Potentially hazardous interactions with other drugs
ACE inhibitors and angiotensin-II antagonists: enhanced hypotensive effect (risk of severe hyperkalaemia).
Analgesics: increased risk of nephrotoxicity with NSAIDs; increased risk of hyperkalaemia, especially with indometacin; antagonism of hypotensive effect.
Antibacterials: avoid concomitant use with lymecycline.
Antidepressants: enhanced hypotensive effect with MAOIs; increased risk of postural hypotension with tricyclics.
Antipsychotics: enhanced hypotensive effect with phenothiazines.
Antihypertensives: enhanced hypotensive effect; increased risk of first dose hypotensive effect of postsynaptic alpha-blockers, e.g. prazosin.
Ciclosporin: increased risk of hyperkalaemia.
Cytotoxics: increased risk of nephrotoxicity and ototoxicity with platinum compounds.
Lithium: reduced excretion of lithium (risk of lithium toxicity).
Potassium salts: increased risk of hyperkalaemia.
Tacrolimus: increased risk of hyperkalaemia.

Metabolism

Triamterene is extensively metabolised apparently via the cytochrome P450 isoenzyme CYP1A2. It is mainly excreted in the urine in the form of metabolites with some unchanged triamterene; variable amounts are also excreted in the bile.

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