Effects of some pyrazinecarboxamides on sodium transport in frog skin.
1 The inhibitory effect of amiloride (N-amidino-3,5-diamino-6-chloropyrazinecarboxamide) on sodium transport in isolated skin of frog has been compared with 17 of its analogues. The dissociation constant of amiloride for passive sodium channels was 181.9 +/- 8.9 nM, and the maximal percentage inhibition of sodium transport was 101.3 +/- 0.4% (means of 123 measurements) when measured at a sodium concentration of 111 mM. 2 The N-benzylamidino and N-o-chlorobenzylamidino compounds had affinities approximately 20 times larger than those for amiloride, and produced maximal inhibition of transport. 3 Substitution of chlorine in the 6-position by other halogens showed that the bromo-compound was equally active to amiloride, whereas the iodo derivative had an affinity equal to 15% of that for amiloride. 4 Substitution in the 5-amino group in 10 compounds reduced the affinities to less than 1% of that of amiloride, without affecting their ability to produce complete inhibition of transport. 5 N-Amidino-3,5-diaminopyrazinecarboxamide was unique in that it produced an unusual concentration-response relationship.
D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D001001:Anura; D001692:Biological Transport / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D011719:Pyrazines / Q000494:pharmacology*; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*
D011719:Pyrazines; D000584:Amiloride; D012964:Sodium