Benzamil
Encyclopedia
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 (benzamil hydrochloride). As amiloride, benzamil has been studied as a possible treatment for cystic fibrosis
, although with disappointing results.
group-containing analog of amiloride. Like amiloride, it is a guanidinium
group-containing pyrazine
derivative
.
Benzamil is closely related to amiloride
. By adding the benzyl group to the nitrogen of the guanidinium
group the activity is increased several hundredfold.
Amiloride works by directly blocking the epithelial sodium channel
(ENaC) thereby inhibiting sodium
reabsorption in the distal convoluted tubule
s and collecting ducts in the kidney
s (this mechanism is the same for triamterene). This promotes the loss of sodium and water from the body, but without depleting potassium
.
ENAC
ENAC may refer to: - a French civil aeronautics academy* Epithelial sodium channel * Italian Civil Aviation Authority...
channel and also a sodium-calcium exchange blocker. It is a potent analog
Analog (chemistry)
In chemistry, a structural analog , also known as chemical analog or simply analog, is a compound having a structure similar to that of another one, but differing from it in respect of a certain component. It can differ in one or more atoms, functional groups, or substructures, which are replaced...
of amiloride
Amiloride
Amiloride is a potassium-sparing diuretic, first approved for use in 1967 , used in the management of hypertension and congestive heart failure. Amiloride was also tested as treatment of cystic fibrosis, but it was revealed inefficient in vivo due to it's short time of action, therefore...
, and is marketed as the 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....
salt (benzamil hydrochloride). As amiloride, benzamil has been studied as a possible treatment for cystic fibrosis
Cystic fibrosis
Cystic fibrosis is a recessive genetic disease affecting most critically the lungs, and also the pancreas, liver, and intestine...
, although with disappointing results.
Structure
Benzamil is a benzylBenzyl
In organic chemistry, benzyl is the term used to describe the substituent or molecular fragment possessing the structure C6H5CH2-. Benzyl features a benzene ring attached to a CH2 group.-Nomenclature:...
group-containing analog of amiloride. Like amiloride, it 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
Amiloride is a potassium-sparing diuretic, first approved for use in 1967 , used in the management of hypertension and congestive heart failure. Amiloride was also tested as treatment of cystic fibrosis, but it was revealed inefficient in vivo due to it's short time of action, therefore...
. By adding the benzyl group to the nitrogen of the 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 the activity is increased several hundredfold.
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 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 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...
.