Inotropic actions of BDF 9148 and DPI 201-106 and their enantiomers in guinea-pig, rat and human atria.
The positive inotropic effects of the sodium channel modulators, DPI 201-106 and BDF 9148, were tested in atrial preparations from guinea-pig, rat and man. In rat, the racemate and S enantiomer of both DPI 201-106 and BDF 9148 displayed the same efficacy as did increased extracellular Ca2+, but in guinea-pig and man, the efficacy varied between 60 and 90% of the maximum Ca2+ response. In all three species, BDF 9148 was significantly more potent than DPI 201-106 by approximately one order of magnitude. The same was evident for the S enantiomers. The R enantiomers did not inhibit the effects of the S enantiomers. We have shown pronounced differences in the efficacy and potency of the enantiomers of DPI 201-206 and BDF 9148, which may be useful for future radioligand binding studies.
Hoey
A
A
Institut für Pharmakologie, Universität-Gesamthochschule-Essen, Germany.
Lehmkuhl
A
A
Sadony
V
V
Ravens
U
U
D000818:Animals; D001384:Azetidines / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006801:Humans; D009200:Myocardial Contraction / Q000187:drug effects*; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D013045:Species Specificity; D013237:Stereoisomerism
D001384:Azetidines; D002316:Cardiotonic Agents; D010879:Piperazines; C071117:BDF 9148; C046261:DPI 201-106