Effects of unsymmetrical ester substituted 1,4-dihydropyridine derivatives and their optical isomers on contraction of smooth muscle

  • R. Towart
  • E. Wehinger
  • H. Meyer
Short Communications


The optical isomers of two nifedipine-like 1,4-dihydropyridine derivates have been synthesised and tested in vitro. The (−)-isomer (S-configuration of both compounds) was more potent than the racemate, which in turn was more potent than the (+)-isomer (R-configuration). The S-configuration isomers are approximately ten times more potent than nifedipine, and may represent the optimal structure and configuration for binding to and inhibiting calcium channels.

Key words

1,4-Dihydropyridines Optical isomers Stereospecificity Nifedipine Calcium antagonists 


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  1. Bayer R, Kalusche D, Kaufmann R, Mannhold R (1975) Inotropic and electrophysiological actions of verapamil and D600 in mammalian myocardium. III Effects of the optical isomers on transmembrane action potentials. Naunyn-Schmiedeberg's Arch Pharmacol 290:81–97Google Scholar
  2. Bolton TB (1979) Mechanism of action of transmitters and other substances on smooth muscle. Physiol Rev 59:606–718Google Scholar
  3. Bossert F, Horstmann H, Meyer H, Vater W (1979) Einfluß der Esterfunktion auf die vasodilatierenden Eigenschaften von 1,4-Dihydro-2,6-dimethyl-4-nitrophenyl-pyridin-3,5-dicarbonsäureestern. Arzneim Forsch (Drug Res) 29:226–229Google Scholar
  4. Daniel EE (1963) On roles of calcium, strontium and barium in contraction and excitability of rat uterine muscle. Arch Int Pharmacodyn 146:298–349Google Scholar
  5. Diem K, Lentner C (1970) (eds) Statistical methods. In: Documenta Geigy, Basel, pp 174–183Google Scholar
  6. Fleckenstein A (1977) Specific pharmacology of calcium in myocardium, cardiac pacemakers, and vascular smooth muscle. Ann Rev Pharmacol Toxicol 17:149–166Google Scholar
  7. Furchgott RF, Bhadrakom S (1953) Reactions of strips of rabbit aorta to epinephrine, isopropylarterenol, sodium nitrite and other drugs. J Pharmacol Exp Ther 108:129–143Google Scholar
  8. Gunther H (1973) NNR-Spektoskopie. G. Thieme Verlag, Stuttgart, p 332Google Scholar
  9. Massingham R (1973) A Study of compounds which inhibit vascular smooth muscle contraction. Eur J Pharmacol 22:75–82Google Scholar
  10. Meyer H, Bossert F, Wehinger E, Stoepel K, Vater W (1981) Synthese and vergleichende pharmakologische Untersuchungen von 1,4-Dihydro-2,6-dimethyl-1-4-(3-nitrophenyl)pyridin-3,5-dicarbonsäureestern mit nicht-identischen Esterfunktionen. Arzneim Forsch (Drug Res) 31:407–409Google Scholar
  11. Rodenkirchen R, Bayer R, Steiner R, Bossert F, Meyer H, Möller E (1979) Structure activity studies on nifedipine in isolated cardiac muscle. Naunyn-Schmiedeberg's Arch Pharmacol 310:69–78Google Scholar
  12. Rosenberger L, Triggle DJ (1978) Calcium, calcium translocation, and specific calcium antagonists. In: Weiss GB (ed) Calcium in Drug Action. Plenum Press, New York, pp 3–31Google Scholar
  13. Sato M, Nagao T, Yamaguchi I, Nakajima H, Kiyomoto A (1971) Pharmacological studies on a new 1,5-benzothiazepine derivative (CRD-401). Arzneim Forsch (Drug Res) 21:1338–1343Google Scholar
  14. Shibanuma T, Iwanani M, Okuda K, Takenaka T, Murakami M (1980) Synthesis of optically active 2-(N-benyl-N-methylamino)-ethyl methyl 2,6-dimethyl-4-(M-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate (nicardipine). Chem Pharm Bull 28:2809–2812Google Scholar
  15. Vater W, Kroneberg G, Hoffmeister F, Kaller H, Meng K, Oberdorf A, Puls W, Schloßmann K, Stoepel K (1972) Zur Pharmakologie von 4-(2-nitrophenyl)-2,6-dimethyl-1,4-dihydropyridin-3,5-dicarbosäuredimethylester (nifedipine, BAY a 1040). Arzneim Forsch (Drug Res) 22:1–14Google Scholar
  16. Wehinger E, Meyer H, Bossert F, Vater W, Towart R, Stoepel K, Kazda S (1979), Bayer AG, German Offenlegungsschrift 2935451 (filed Setember 1st, 1979).Google Scholar

Copyright information

© Springer-Verlag 1981

Authors and Affiliations

  • R. Towart
    • 1
  • E. Wehinger
    • 2
  • H. Meyer
    • 2
  1. 1.Institut für PharmakologieWuppertal 1Germany
  2. 2.Chemisch-Wissenschaftliches Laboratorium Pharma Bayer AGWuppertal 1Germany

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