Interference of N-(1-[4-(4-fluorophenoxy)butyl]-piperidinyl)-N-methyl- 2-benzothiazolamine with Na+/H+ exchange and Na+/Ca2+ exchange in purified cardiac sarcolemmal membranes.
The effect of R 56865 (N-[1-[4-(4-fluorophenoxy)butyl]-piperidinyl]-N-methyl-2- benzothiazolamine, CAS 104606-13-5) on Na+/H+ exchange and Na+/Ca2+ exchange was studied in isolated cardiac sarcolemmal vesicles. R 56865 inhibited Na+/H+ exchange with an ED50 of 180 mumol/l at a concentration of 0.05 mmol/l Na+. The potency of R 56865 decreased with increasing concentrations of Na+. Na+/Ca2+ exchange was also inhibited. The ED50 amounted to 45 mumol/l. This ED50 was close to that of the reference compound dichlorobenzamil (ED50 = 27 mumol/l). The inhibitory potency of R 56865 on Na+/H+ and Na+/Ca2+ exchange is far too low to explain the already reported beneficial effects of this inhibitor of Na+ and Ca+ overload during ouabain intoxication and ischemia and reperfusion.
Scheufler
E
E
Janssen Research Foundation, Neuss, Fed. Rep. of Germany.
Heers
C
C
Wilffert
B
B
Peters
T
T
Pierce
G N
GN
D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D052160:Benzothiazoles; D002118:Calcium / Q000378:metabolism*; D002417:Cattle; D006321:Heart / Q000187:drug effects; D006859:Hydrogen / Q000378:metabolism*; D066298:In Vitro Techniques; D007474:Ion Exchange; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism*; D010042:Ouabain / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology*; D012508:Sarcolemma / Q000187:drug effects / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*; D013844:Thiazoles / Q000494:pharmacology*
D052160:Benzothiazoles; D010880:Piperidines; D013844:Thiazoles; C041470:3',4'-dichlorobenzamil; D010042:Ouabain; D000584:Amiloride; D006859:Hydrogen; C054551:R 56865; D012964:Sodium; D002118:Calcium