Amiloride and its analogs as tools to inhibit Na+ transport via the Na+ channel, the Na+/H+ antiport and the Na+/Ca2+ exchanger.
Amiloride analogs inhibit a number of transmembrane Na+ transport systems: 1) the epithelium Na+ channel, 2) the Na+/H+ exchange system and 3) the Na+/Ca2+ exchange system. Structure--activity relationships using amiloride derivatives with selected modification of each of the functional groups of the molecule indicate that the 3 Na+ transporting systems have distinct pharmacological profiles. 5-N Disubstituted derivatives of amiloride, such as ethylisopropylamiloride are the most potent inhibitors of the Na+/H+ exchange system. Conversely, amiloride derivatives that are substituted on the guanidino moiety, such as phenamil, are potent inhibitors of the epithelium Na+ channel. It is thus possible, by using selected amiloride derivatives to inhibit selectively one or another of the Na+ transport systems.
Frelin
C
C
Centre National de la Recherche Scientifique, Nice, France.
Barbry
P
P
Vigne
P
P
Chassande
O
O
Cragoe
E J
EJ
Lazdunski
M
M
D000584:Amiloride / Q000378:metabolism* / Q000494:pharmacology; D000663:Amphibians; D000818:Animals; D001692:Biological Transport; D002352:Carrier Proteins / Q000378:metabolism*; D002645:Chickens; D004848:Epithelium / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D015222:Sodium Channels / Q000187:drug effects*; D019831:Sodium-Calcium Exchanger; D017923:Sodium-Hydrogen Exchangers
D002352:Carrier Proteins; D015222:Sodium Channels; D019831:Sodium-Calcium Exchanger; D017923:Sodium-Hydrogen Exchangers; D000584:Amiloride