Effects of beta-adrenoceptor blocking agents of N-tertiary butyl derivatives on maximum upstroke velocity of action potential in guinea-pig papillary muscles.
The effects of bufetolol (27.8-138.9 mumol/l), bunitrolol (70.2-351.1 mumol/l), bupranolol (16.2-100 mumol/l), carteolol (60.7-607 mumol/l), D32 (17.3-100 mumol/l), penbutolol (1.5-29.4 mumol/l) and timolol (115.5 and 231.2 mumol/l) on action potentials were investigated in isolated guinea-pig papillary muscles. All these beta-adrenoceptor blocking agents of teritary butyl aminopropranol derivatives produced a concentration-dependent reduction of Vmax at driving rates of 1 Hz, 0.027 Hz and 4 Hz. The reduction was frequency-dependent but at all the rates penbutolol was highest in potency, as estimated by ED30 (0.027 Hz) and ED 50 values (1 and 4 Hz), followed by bupranolol, D-32, bufetolol and bunitrolol. These were followed in turn by timolol and carteolol in ED30 at 0.027 Hz and ED50 at 1 Hz, but by carteolol and timolol in ED50 at 4 Hz. Each log (1/ED) value is a linear function of log n-octanol/water partition coefficient (log P). The slope and intercept (the value at log P = 0) of the line of log (1/ED50) at 4 Hz are steeper and higher, respectively, than those of the lines at the other frequencies. The time course of recovery of Vmax during diastole was studied by assessing Vmax in premature responses at 0.027 Hz, being approximated by a single exponential function. The time constants of recovery (tau) and intercepts (Ao: the value extrapolated to the time of APD90 of the conditioning responses) at the level of ED50 and at 100 mumol/l of the drugs were thus estimated.(ABSTRACT TRUNCATED AT 250 WORDS)
D000200:Action Potentials / Q000187:drug effects*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects; D010210:Papillary Muscles / Q000187:drug effects* / Q000502:physiology; D012964:Sodium / Q000378:metabolism; D013329:Structure-Activity Relationship
D000319:Adrenergic beta-Antagonists; D007473:Ion Channels; D012964:Sodium