Effects of amiloride and its analogues on [3H]batrachotoxinin-A 20-alpha benzoate binding, [3H]tetracaine binding and 22Na influx.
The ability of amiloride and its analogues to inhibit [3H]batrachotoxinin-A 20-alpha benzoate [( 3H]BTX-B) and [3H]tetracaine binding to rat synaptosomes and to a rat heart membrane preparation was tested. Their ability to inhibit 22Na influx was determined with rat synaptosomes. 5-N-substituted analogues were generally more potent in inhibiting [3H]BTX-B and [3H]tetracaine binding than compounds substituted on the guanidine group. However, the inhibition was not competitive. Amiloride and some of its analogues were as active or more active in inhibiting [3H]tetracaine binding than they were in inhibiting [3H]BTX-B binding. 22Na influx was inhibited with the same relative potencies as [3H]BTX-B binding and a good correlation was found between the two inhibitions. These results show an effect of amiloride and its analogues on the voltage-sensitive Na+ channels, which could partly explain the inotropic effects of these drugs.
Velly
J
J
Institut de Pharmacologie (UA 589 CNRS) Faculté de Médecine, Strasbourg, France.
Grima
M
M
Decker
N
N
Cragoe
E J
EJ
Schwartz
J
J
D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D001496:Batrachotoxins / Q000378:metabolism*; D001667:Binding, Competitive / Q000187:drug effects; D066298:In Vitro Techniques; D009206:Myocardium / Q000378:metabolism; D009498:Neurotoxins / Q000378:metabolism*; D011526:Protoveratrines / Q000494:pharmacology; D051381:Rats; D012964:Sodium / Q000378:metabolism*; D012979:Sodium Radioisotopes; D013574:Synaptosomes / Q000378:metabolism; D013748:Tetracaine / Q000378:metabolism*
D001496:Batrachotoxins; D009498:Neurotoxins; D011526:Protoveratrines; D012979:Sodium Radioisotopes; D013748:Tetracaine; C031775:batrachotoxinin A 20-alpha-benzoate; D000584:Amiloride; D012964:Sodium