Cardiovascular effects of the novel potassium channel opener (3S,4R)-3-hydroxy-2,2-dimethyl-4-(2-oxo- 1-pyrrolidinyl)-6-phenylsulfonylchromane hemihydrate.
Cardiovascular effects of the novel potassium channel opener (3S,4R)-3-hydroxy-2,2-dimethyl-4-(2-oxo-1-pyrrolidinyl)-6- phenylsulfonylchromane hemihydrate (Hoe 234, CAS 132014-21-2) were investigated in rats, dogs and monkeys. In all species and independent of the route of administration Hoe 234 lowered systemic blood pressure accompanied with increases in heart rate. In rats after intravenous (i.v.) application Hoe 234 was 3 times more potent than cromakalim and its effects were reduced by pretreatment with the potassium channel blocker glibenclamide. Following intraduodenal application again Hoe 234 was more potent but mean arterial blood pressure (MAP) decreased more slowly and maximal effects were obtained later than after cromakalim. Oral administration of either single or repeated doses, however, revealed a somewhat higher potency for cromakalim. In anesthetized dogs Hoe 234 i.v. reduced MAP more potently than cromakalim whereas changes in heart rate were less pronounced. Cardiac output was increased and total peripheral resistance decreased for either agent. These results show that Hoe 234 is a novel potassium channel opener lowering blood pressure in animals due to peripheral vasodilation. It compares favourable with known potassium channel openers except for oral administration.
Linz
W
W
Hoechst Aktiengesellschaft, Frankfurt/Main, Fed. Rep. of Germany.
Klaus
E
E
Albus
U
U
Becker
R
R
Mania
D
D
Englert
H C
HC
Schölkens
B A
BA
D000284:Administration, Oral; D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002839:Chromans / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007271:Injections, Intradermal; D007275:Injections, Intravenous; D008253:Macaca mulatta; D008297:Male; D009125:Muscle Relaxants, Central / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects*; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D017207:Rats, Sprague-Dawley
D002839:Chromans; D009125:Muscle Relaxants, Central; D015221:Potassium Channels; D011759:Pyrrolidines; C075012:rilmakalim