By W. Lochner (auth.), Professor Dr. Wilhelm Lochner, Wolfgang Braasch, Günther Kroneberg (eds.)

The First Adalat Symposium held in Tokyo in 1973, awarded vital experimental and scientific effects which were accumulated in Europe and Japan with the recent coronary healing agent. the eu scientists had a chance to debate the issues and effects in my view with their jap colleagues. the second one Adalat Symposium used to be held in Amsterdam inside a yr with the aim of bringing jointly normally scientists inside Europe. the consequences mentioned in Tokyo were prolonged and supplemented via extra reports. Contributions in simple technological know-how are provided, yet most crucial are these scientific experiences, which aid and expand facts of the drug's efficacy in people. The editors desire to show their appreciation to all these answerable for contributing to this record and, particularly, to Dr. M. SPENGLER, Dr. F. EBNER and Dr. ok. BRANDAU for his or her editorial support, and to Dr. W. BOTTGER for the guidance of the topic Index. we are hoping that this book may be a worthy contribution towards conveying info to physicians and scientists. DiisseldorfjWuppertal, Autumn 1975 W. LOCHNER' W BRAASCH' G. KRONEBERG Contents creation: W. LOCHNER current foundation of Coronary remedy: W. LOCHNER. With eleven Figures 2 consultation I. Chemistry and Experimental Pharmacology (Chairmen: A. FLECKENSTEIN and ok. LANDMARK) Pharmacology of Nifedipine: G. KRONEBERG. With eight Figures 12 dialogue feedback 19 The Chemistry of Nifedipine: F. BOSSERT. With nine Figures 20 Pharmacokinetics of Adalat in Animal Experiments: ok. PATZSCHKE, B.

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Zur Pharmakologie von 4-(2' -Nitrophenyl)-2,6dimethyl-l,4-dihydropyridin-3,5-dicarbonsliuredimethylester (Nifedipine, BAY a 1040). -Forsch. ) 22, 1-14 (1972). 11. : Effects of agents which inhibit the slow channel on sinus node automaticity and atrioventricular conduction in the dog. Circulation Res. 34, 184-192 (1974). 12. : Action of manganese ions and"tetrodotoxin on atrioventricular nodal transmembrane potentials in isolated rabbit hearts. Circulation Res. 32,447-454 (1973). Discussion Remarks FLECKENSTEIN: In our experiments on anesthetized guinea pigs, we injected verapamil, D 600, and nifedipine and could not detect principal differences in their influence on the atrioventricular (A-V) node.

The next move in the synthetic program followed logically: the introduction into the molecule of such carboxylic ester functions as were known to be resistant to hydrolysis. Examples are shown in Fig. 3. Sterically hindered esters of type (5) are known to be resistant to normal sa"ponifica tion conditions, the ester group being screened by the substituents R 1 und R 2 . Also resistant are amido-carboxylic esters (6) where the electronic effect of the nitrogen hinders attack at the carbonyl carbon atom.

During this time an equivalent concentration of approx. 02 Ilg/ml was present in the arterial plasma. 05 Ilg/ml. That means that 32 K. P ATZSCHKE et al. even very small concentrations of drug are sufficient to produce a pharmacodynamic effect. 03 to 3 mg/kg) and dogs (1 mg/kg). In rats more than 90% of the orally administered substance was absorbed. Of the orally or intravenously administered activity, 50 to 70% was excreted via the kidneys and 30 to 50% via the feces. The activity-content in the tissues (body excluding gastro-intestinal tract), 48 h after administration, was approx.

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