EFFECTS OF SOME PYRAZINECARBOXAMIDES ON SODIUM TRANSPORT IN FROG SKIN

The inhibitory effect of amiloride (N‐amidino‐3,5‐diammo‐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. The N‐benzylamidino and N‐o‐chlorobenzylamidino compounds had affinities approximately 20 times larger than those for amiloride, and produced maximal inhibition of transport. 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 affnity equal to 15% of that for amiloride. 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. N‐Amidino‐3,5‐diaminopyrazinecarboxamide was unique in that it produced an unusual concentration‐response relationship.