ISSN:
1432-1912
Keywords:
Cardiac action potential
;
Fast Na+ system of the cardiac membrane
;
β-Adrenoceptor blocking agents
;
Structure-activity relation
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary The effects of atenolol (2–5 mmol/l), sotalol (1–2 mmol/l) and pamatolol (0.1–1 mmol/l), together with N-tertiary butyl phenoxypropanolamines with o-methyl (D-2T: 50–100 μmol/l) m-methyl (D-3T: 50–100 μmol/l) and p-methyl (D-4T:100–200 μmol/l) group as well as with o,p-methyl groups (D-24T) (50–100 μmol/l) on action potentials (APs) were investigated in isolated guinea-pig papillary muscles. All the drugs in these concentrations produced a concentration-dependent reduction of the maximum upstroke velocity (V max). The reduction ofV max in premature APs induced by stimuli interpolated between the basic driving rate of 0.25, 0.1 or 0.027 Hz decayed exponentially during diastolic intervals. The time constants of these decay processes τ for atenolol, pamatolol and sotalol ranged between 260–541 ms, those for D-3T and D-4T between 655–1,166 ms, and D-2T and D-24T between 1,565–1,931 ms. A drug which provided larger τ values caused the reduction ofV max in a wider range of the frequency. With respect to the aryloxypropanolamine derivatives so far studied (Sada and Ban 1980, 1981 a, b; Sada et al. 1983) fairly good correlations were found as follows: between logn-octanol/water partition coefficient (logP) and ED20 at 0.25 Hz, ED30 at 1 and 4 Hz for 11–14 compounds; between logP and resting block, between molecular weight and A o c i.e. the value extrapolated to the time of APD90 of the conditioning response relative to the predrugV max value which may represent a fraction of channels blocked per AP for 100 μmol/l of 20–22 compounds. With respect to 8 compounds with methyl substituents in the benzene ring or amine part the ortho methyl group makes a major contribution to increase the resting block and to increase log τ values.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00695196
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