Electrophysiological effects of amosulalol, a new alpha- and beta-adrenoceptor blocker, in isolated rabbit papillary muscles.
The electrophysiological effects of amosulalol, a newly developed alpha- and beta-adrenoceptor blocking agent, were examined and compared with those of labetalol, prazosin and propranolol in isolated rabbit papillary muscles by means of standard microelectrode techniques. Amosulalol above 3 microM produced a concentration-dependent decrease in the maximum rate of depolarization (Vmax) and an increase in action potential duration (APD). Labetalol and prazosin produced a similar APD prolongation, and Vmax was depressed by all these drugs in a concentration-dependent manner. The depressant action of these drugs on Vmax was enhanced by increasing the stimulation rate from 0.25 to 2.0 Hz. In the presence of these drugs the Vmax declined exponentially to a new plateau level (rate-dependent block) and the onset of the rate dependent block for amosulalol at 1 Hz was similar to that for labetalol and propranolol, and faster than that for prazosin. The time constants of the recovery from rate-dependent block for amosulalol, labetalol and prazosin were considerably slower than that for propranolol. These results suggest that amosulalol possesses class I and III antiarrhythmic properties and the recovery from the rate-dependent block of Vmax is relatively slow with this drug.
Tohse
N
N
Nakaya
H
H
Kanno
M
M
D000200:Action Potentials / Q000187:drug effects; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D004558:Electric Stimulation; D004983:Ethanolamines / Q000494:pharmacology*; D005260:Female; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D007700:Kinetics; D007741:Labetalol / Q000494:pharmacology; D008297:Male; D010210:Papillary Muscles / Q000187:drug effects; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011817:Rabbits; D013997:Time Factors; D000096926:Benzenesulfonamides
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D004983:Ethanolamines; D007741:Labetalol; D011224:Prazosin; D011433:Propranolol; C032473:amosulalol; D000096926:Benzenesulfonamides