Amiloride is a potassium-sparing diuretic, first approved for use in 1967 (then known as MK 870), used in the management of hypertension

Hypertension

Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...

 and congestive heart failure

Congestive heart failure

Heart failure often called congestive heart failure is generally defined as the inability of the heart to supply sufficient blood flow to meet the needs of the body. Heart failure can cause a number of symptoms including shortness of breath, leg swelling, and exercise intolerance. The condition...

. Amiloride was also tested as treatment of cystic fibrosis

Cystic fibrosis

Cystic fibrosis is a recessive genetic disease affecting most critically the lungs, and also the pancreas, liver, and intestine...

, but it was revealed inefficient in vivo due to it's short time of action, therefore longer-acting ENaC inhibitors may prove more effective, e.g. Benzamil

Benzamil

Benzamil or benzyl amiloride is a potent blocker of the ENaC channel and also a sodium-calcium exchange blocker. It is a potent analog of amiloride, and is marketed as the hydrochloride salt...

.

Structure

Amiloride is a guanidinium

Guanidine

Guanidine is a crystalline compound of strong alkalinity formed by the oxidation of guanine. It is used in the manufacture of plastics and explosives. It is found in urine as a normal product of protein metabolism. The molecule was first synthesized in 1861 by the oxidative degradation of an...

 group containing pyrazine

Pyrazine

Pyrazine is a heterocyclic aromatic organic compound with the chemical formula C4H4N2.Pyrazine is a symmetrical molecule with point group D2h. Derivatives like phenazine are well known for their antitumor, antibiotic and diuretic activity. Pyrazine is less basic in nature than pyridine, pyridazine...

 derivative

Derivative (chemistry)

In chemistry, a derivative is a compound that is derived from a similar compound by some chemical or physical process. In the past it was also used to mean a compound that can be imagined to arise from another compound, if one atom is replaced with another atom or group of atoms, but modern...

.

Mechanism of action

Amiloride works by directly blocking the epithelial sodium channel

Epithelial sodium channel

The epithelial sodium channel is a membrane-bound ion-channel that is permeable for Li+-ions, protons and especially Na+-ions. It is a constitutively active ion-channel...

 (ENaC) thereby inhibiting sodium

Sodium

Sodium is a chemical element with the symbol Na and atomic number 11. It is a soft, silvery-white, highly reactive metal and is a member of the alkali metals; its only stable isotope is 23Na. It is an abundant element that exists in numerous minerals, most commonly as sodium chloride...

 reabsorption in the late distal convoluted tubule

Distal convoluted tubule

The distal convoluted tubule is a portion of kidney nephron between the loop of Henle and the collecting duct system.- Physiology :It is partly responsible for the regulation of potassium, sodium, calcium, and pH...

s, connecting tubules, and collecting ducts in the kidney

Kidney

The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...

s (this mechanism is the same for triamterene). This promotes the loss of sodium and water from the body, but without depleting potassium

Potassium

Potassium is the chemical element with the symbol K and atomic number 19. Elemental potassium is a soft silvery-white alkali metal that oxidizes rapidly in air and is very reactive with water, generating sufficient heat to ignite the hydrogen emitted in the reaction.Potassium and sodium are...

. The drug is often used in conjunction with thiazide

Thiazide

Thiazide is a term used to describe a type of molecule and a class of diuretics often used to treat hypertension and edema ....

 (e.g. co-amilozide

Co-amilozide

Co-amilozide is a non-proprietary name used to denote a combination of amiloride and hydrochlorothiazide. Co-amilozide is used in the treatment of hypertension and congestive heart failure with the tendency of the thiazide to cause low potassium levels offset by the potassium-sparing effects of...

) or loop diuretic

Loop diuretic

Loop diuretics are diuretics that act on the ascending loop of Henle in the kidney. They are primarily used in medicine to treat hypertension and edema often due to congestive heart failure or renal insufficiency...

s (e.g. co-amilofruse

Co-amilofruse

Co-amilofruse is a non-proprietary name used to denote a combination of amiloride and the formerly named frusemide . Co-amilofruse in the treatment of fluid retention , either in the legs or on the lungs...

). Due to its potassium-sparing capacities, hyperkalemia

Hyperkalemia

Hyperkalemia refers to the condition in which the concentration of the electrolyte potassium in the blood is elevated...

 (high blood potassium levels) is occasionally observed in patients taking amiloride. The risk is high in concurrent use of ACE inhibitor

ACE inhibitor

ACE inhibitors or angiotensin-converting enzyme inhibitors are a group of drugs used primarily for the treatment of hypertension and congestive heart failure...

s or spironolactone

Spironolactone

Spironolactone , commonly referred to as simply spiro, is a diuretic and is used as an antiandrogen.It is a synthetic 17-lactone drug that is a renal competitive aldosterone antagonist in a class of pharmaceuticals called...

. Patients are also advised not to use potassium-containing salt replacements. Amiloride also carries the risk of developing an acidosis

Acidosis

Acidosis is an increased acidity in the blood and other body tissue . If not further qualified, it usually refers to acidity of the blood plasma....

.

A fraction of the effects of amiloride is inhibition of cyclic GMP-gated cation channels in the inner medullary collecting duct.

Amiloride has a second action on the heart, blocking Na+/H+ exchangers Sodium-hydrogen antiporter 1

Sodium-hydrogen antiporter 1

The sodium-hydrogen antiporter 1 also known as sodium/hydrogen exchanger 1 or SLC9A1 is an isoform of sodium–hydrogen antiporter that in humans is encoded by the SLC9A1 gene.- Function :...

 or NHE-1. This minimizes reperfusion injury in ischemic attacks.

Acid-sensing ion channel

Acid-sensing ion channel

Acid-sensing ion channels are neuronal voltage-insensitive cationic channels activated by extracellular protons. ASIC proteins are a subfamily of the ENaC/Deg superfamily of proteins. To date six proteins of the ASIC family have been identified that arise from four genes, ASIC1, ASIC2, ASIC3, and...

s (ASICs) are also sensitive to inhibition by amiloride. ASICs are involved in nociceptor

Nociceptor

A nociceptor is a sensory receptor that responds to potentially damaging stimuli by sending nerve signals to the spinal cord and brain. This process, called nociception, usually causes the perception of pain.-History:...

 responses to pH .

Formulations and trade names

• amiloride hydrochloride
  Hydrochloride
  In chemistry, hydrochlorides are salts resulting, or regarded as resulting, from the reaction of hydrochloric acid with an organic base . This is also known as muriate, derived from hydrochloric acid's other name: muriatic acid....
  
  
  • Midamor (U.S.)

• co-amilozide
  Co-amilozide
  Co-amilozide is a non-proprietary name used to denote a combination of amiloride and hydrochlorothiazide. Co-amilozide is used in the treatment of hypertension and congestive heart failure with the tendency of the thiazide to cause low potassium levels offset by the potassium-sparing effects of...
  
  (amiloride hydrochloride with hydrochlorothiazide)