Species differences in the positive inotropic response to DPI 201-106, a novel cardiotonic agent.
The positive inotropic activity of the novel cardiotonic DPI 201-106 was investigated in rat and guinea pig isolated hearts. For comparative purposes, the adenylate cyclase stimulant forskolin and the sodium channel agonist veratridine were also evaluated in both species. DPI 201-106 and veratridine produced greater inotropic effects in rat hearts than in guinea pig hearts, whereas forskolin produced comparable effects. In both species the inotropic response to DPI 201-106 and veratridine, but not forskolin, was reversed by the sodium channel antagonist tetrodotoxin. These results confirm that the positive inotropic effect of DPI 201-106 is due to stimulation of the sodium channel and demonstrate for the first time that species differences exist in the inotropic response to this novel cardiotonic drug.
Haleen
S J
SJ
Department of Pharmacology, Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, Ann Arbor, MI 48105.
Steffen
R P
RP
Weishaar
R E
RE
D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D005576:Colforsin / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D015222:Sodium Channels / Q000187:drug effects; D013045:Species Specificity; D013779:Tetrodotoxin / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology
D002316:Cardiotonic Agents; D010879:Piperazines; D015222:Sodium Channels; D005576:Colforsin; D013779:Tetrodotoxin; D014701:Veratridine; C046261:DPI 201-106