Effects of various structurally related beta-adrenoceptor blocking agents on maximum upstroke velocity of action potential in guinea-pig papillary muscles.
The effects of indenolol (7.0-100 mumol/l), befunolol (15.3-250 mumol/l), metoprolol (58.4-1000 mumol/l), Kö707 (7.3-100 mumol/l), D-25 (3.7-100 mumol/l) and Kö1313 (73.9-1000 mumol/l) on action potentials were investigated in isolated guinea-pig papillary muscles. All these aryloxyisopropylaminopropanol derivatives produced a concentration-dependent reduction of V max at a basic rate of 1 Hz. The reduction was less prominent when interstimulus intervals were prolonged. The time course of recovery of V max during diastole was studied by assessing V max in premature responses at 0.25, 0.1 and 0.027 Hz and in responses after interrupting driving stimuli of 1 Hz. The recovery process was approximated by a single exponential function prominent when interstimulus intervals were prolonged. The time course of recovery of V max during diastole was studied by assessing V max in premature responses at 0.25, 0.1 and 0.027 Hz and in responses after interrupting driving stimuli of 1 Hz. The recovery process was approximated by a single exponential function prominent when interstimulus intervals were prolonged. The time course of recovery of V max during diastole was studied by assessing V max in premature responses at 0.25, 0.1 and 0.027 Hz and in responses after interrupting driving stimuli of 1 Hz. The recovery process was approximated by a single exponential function. The results, together with those reported previously (Sada and Ban 1980, 1981), revealed: (1) a significant correlation between potencies of these derivatives for depression of V max at 0.027, 0.25, 1 and 5 Hz and their log n-octanol/water partition coefficients (log P): (2) The time constants of recovery were relatively concentration independent and correlated significantly with the molecular weights. The results suggest that the potency of these drugs for the depression of V max was mainly determined by log P, being modified secondarily by the time constants of recovery which are intimately associated with the molecular weights.
D000200:Action Potentials / Q000187:drug effects; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D004558:Electric Stimulation; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007192:Indenes / Q000494:pharmacology; D008790:Metoprolol / Q000494:pharmacology; D008970:Molecular Weight; D010210:Papillary Muscles / Q000187:drug effects / Q000502:physiology*; D011412:Propanolamines / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000319:Adrenergic beta-Antagonists; D007192:Indenes; D011412:Propanolamines; C006034:befunolol; C002989:indenolol; D008790:Metoprolol