Amiloride

Amiloride

Clinical data
Trade names	Midamor, others
AHFS/Drugs.com	Monograph
Pregnancy category	US: B (No risk in non-human studies)
Routes of administration	Oral
ATC code	C03DB01 (WHO)
Legal status
Legal status	UK: POM (Prescription only) US: ℞-only
Pharmacokinetic data
Bioavailability	Readily absorbed, 15–25%
Protein binding	~23%
Metabolism	Nil
Onset of action	2 hours (peak at 6–10 hours, duration ~24 hours)
Biological half-life	6 to 9 hours
Excretion	Urine (20–50%), feces (40%)
Identifiers
IUPAC name 3,5-diamino-6-chloro-N-(diaminomethylene)pyrazine-2-carboxamide
Synonyms	MK-870
CAS Number	2016-88-8 Y
PubChem (CID)	16231
IUPHAR/BPS	2421
DrugBank	DB00594 Y
ChemSpider	15403 Y
UNII	7M458Q65S3 Y
KEGG	D07447 Y
ChEBI	CHEBI:2639 Y
ChEMBL	CHEMBL945 Y
ECHA InfoCard	100.018.205
Chemical and physical data
Formula	C6H8ClN7O
Molar mass	229.627 g/mol
3D model (Jmol)	Interactive image
SMILES Clc1nc(C(=O)\N=C(/N)N)c(nc1N)N
InChI InChI=1S/C6H8ClN7O/c7-2-4(9)13-3(8)1(12-2)5(15)14-6(10)11/h(H4,8,9,13)(H4,10,11,14,15) Y Key:XSDQTOBWRPYKKA-UHFFFAOYSA-N Y
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Amiloride, sold under the trade name Midamor among others, is a potassium-sparing diuretic. It is used most often in the management of hypertension and congestive heart failure.

Amiloride was first approved for use in 1967. It is on the World Health Organization's List of Essential Medicines, the most important medications needed in a basic health system.

Contraindications

Amiloride is contraindicated in patients with Addison's disease, hyperkalaemia, hyponatremia and anuria.

Adverse effects

• Common adverse effects:
  • Hyperkalemia
  • Hyponatremia
  • Dehydration
  • Headache
  • Polyuria
  • Fatigue
  • Nausea
  • Vomiting
  • Stomach pain
  • Dizziness
  • Anorexia
  • Skin Rash

Structure

Amiloride's chemical structure contains a guanidinium group containing pyrazine derivative.

Mechanism of action

Amiloride works by directly blocking the epithelial sodium channel (ENaC) thereby inhibiting sodium reabsorption in the late distal convoluted tubules, connecting tubules, and collecting ducts in the nephron. This promotes the loss of sodium and water from the body, but without depleting potassium. The drug is often used in conjunction with a thiazide diuretic to counteract the potassium-sparing effect. Due to its potassium-sparing capacities, hyperkalemia can occur. The risk of developing hyperkalemia is high in patients who are also on ACE inhibitors, angiotensin II receptor antagonists, other potassium-sparing diuretics like spironolactone, or any potassium-containing supplements.

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 or NHE-1. This minimizes re-perfusion injury in ischemic attacks.

Amiloride also blocks the Na⁺/H⁺ antiporter on the apical surface of the proximal tubule cells, in the nephron, abolishing more than 80% of the action of angiotensin II on the secretion of hydrogen ions in proximal tubule cells.

Amiloride was also tested as treatment of cystic fibrosis, but it was revealed inefficient in vivo due to its short time of action, therefore longer-acting epithelial sodium channel (ENaC) inhibitors may prove more effective, e.g. benzamil.

Acid-sensing ion channels (ASICs) are also sensitive to inhibition by amiloride. ASICs are involved in nociceptor responses to pH.

Society and culture

It is on the World Health Organization's List of Essential Medicines, the most important medication needed in a basic health system.

Amiloride is listed on the world anti-doping agency's list of banned substances, it is considered a masking agent.

Formulations and trade names

• Amiloride hydrochloride
  • Midamor (U.S.)
• Co-amilozide (amiloride hydrochloride with hydrochlorothiazide)
• Co-amilofruse (amiloride hydrochloride with furosemide)
• Amiloride hydrochloride with cyclopenthiazide
• Amiloride hydrochloride with bumetanide