Prajmaline as a calcium antagonist in cardiac tissue

J Mol Cell Cardiol 19 (Supplement III) (1987) 88

EFFECTS OF 505fL ~;]W CARDIOTONIC

AGENTS ~[!TH VASODILATOR

Angela hagen I) and V. qa ~ en 2) . I) PnarmacoloEicgl , Pharmaceutical

Kombinat

!}ERIdED, Berlin/GD~

and

ACTIVIIX.

Research Institute of the

Z)institute

of Drug Research

of Academ~ of Science of the GDR/Berlin fhe in vitro cardiac effects of some new p}ridine derivatives were investigated in guinea pig atria and Len~endorff perfused heart of guinea pig. Several 2-Oxaalk~Imq*ino-j 2-0xaalkox N- and 2-Aminoalk~lamino-~-cNan- 5(/~-p~ridin~l)-p~ridines exert a spectrum of different pharmacological effects which comprise a concentration-dependent increase in force of contraction and a dilatation of coronar~ vessels. Various effects were observed re~;arding spontaneous heart rate. In conclusion of our results, several compounds represent a hove[type of cardiobonic agents, Structure-Activity Relationships are discussed.

89

P R A J M A L I N E AS A C A L C I U M A N T A G O N I S T IN C A R D I A C T I S S U E . O. H~la, J.Gy. Papp, L. Szekeres. Department of Pharmacology, University Medical School, Szeged, Hungary Several antiarrhythnics exert rather complex effects on the electrical and mechanical activity of the myocardium. The aim of the present study was to examine whether prajmaline, which is known to block preferentially the fast sodium inward current (Class I action), has some subsidiary features associated with the restriction of calcium-dependent functions in cardiac tissue (Class IV action) i.e. whether this antiarrhythmic drug is capable of inhibiting the calci~n-induced enhancement in the sino-atrial- (SA) and atrio-ventricular-nodal (AV) pacemaker rate and in the contractile force of the atrial and ventricular myocardi~n. Spontaneously firing SA and AV portions, right anterior papillary n~ascles and left atrial trabeculae were prepared frcm the heart of young rabbits. The calcium concentration-response relationships were established in the range of i . O to 6.0 n~ol/l extracellular calci~n concentration under control conditions and in the presence of O.i, 0.2 and 0.5 mg/l prajmaline. The calcit~n-induced increase in the SA- and AV-nodal pacemaker rates was clearly diminished by O.i to 0.5 r~/l prajmaline in a concentration-dependent manner. The same applies to the inhibition by prajmaline of the positive inotropic action of calci~n in atrial trahecular and ventricular papillary muscle. It is suggested that functional cardiac receptors for prajmaline exist in association with both sodium and calciL~n channels.

90

Suppression of Cultured Vascular Smooth Muscle Cell Proliferation by Fendilin H~mmerle H., Betz E. Institut of Physiology I, University of TObingen, Gmelinstr.5, D-7400 TObingen, FRG In the initial stage of atherosclerotic plaque development smooth muscle cells from the media migrate into the subendothelial space (1,2). After proliferation these smooth muscle cells form in a few weeks intimal thickenings and atherosclerotic plaques. In the present study we tested the influence of Fendilin on the proliferation of diploid smooth muscle cell cultures.

Fendilin reveals a dose dependent suppressiv

effect on the proliferation of smooth muscle cells from the media of rabbit thoracic and abdominal aorta. The ID(50) of Fendilin was at a concentration of Ixi0

mol i

whereas at a concentration of 5xlO -6 mol 1-1 no antiproliferativ effect was dedectable. Our finding suggest that Fendilin may suppress the smooth muscle cell proliferation in vivo and therefore may influence the atherosclerotic plaque development. 1.Wissler et al., Circ.36:1-4

(1967) 2.Ross at al., Science 180:1332-1339

S.30

(1973)