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Arzneimittelforschung 2012; 62(07): 345-350
DOI: 10.1055/s-0032-1312617
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

The Novel Phenylpropiophenone Derivates Induced Relaxation of Isolated Rat Aorta

B. Ivković
1   Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia
,
S. Vladimirov
1   Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia
,
R. Novaković
2   Department of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
,
V. Čupić
3   Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Belgrade, Belgrade, Serbia
,
H. Heinle
4   Institute of Physiology, University of Tübingen, Tübingen, Germany
,
L. Gojković-Bukarica
2   Department of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
› Author Affiliations
Further Information

Publication History

received 04 January 2012

accepted 23 April 2012

Publication Date:
24 May 2012 (online)

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Abstract

Our aim was to define how different chemical properties of newly developed phenylpropiophenone derivates (PhPds) influenced their potency and efficacy to relax rat aorta. A contribution of ion channels in the PhPds and propafenone mechanism of vasodilatation was tested. PhPds were syntethysed by substitution in the benzyl moiety with -F, -CH3 or -CF3 groups on the ortho or para position. The vasodilatation by PhPds was examined on the rings of rat aorta precontracted with phenylephrine. In order to test involvement of voltage-gated Na+ and K+ channels and L-type Ca2+ channels in a mechanism of action of PhPds, we used their blockers: lidocaine, nifedipine and 4-aminopiridine, respectively. Aorta was more sensitive to 5-ortho-trifluoromethyl derivate than to propafenone and other PhPds. The 5-para-methyl derivate had lower potency and efficacy than propafenone and other PhPds. Lidocaine did not influenced relaxation induced by PhPds, but slightly inhibited the effect of propafenone. The 4-aminopiridine only inhibited relaxation induced by 5-para-methyl derivate. Nifedipine inhibited relaxation of the rat aorta induced by 5-ortho-trifluoromethyl derivate and by propafenone. Introduction of 5-ortho-trifluoromethyl and 5-para-methyl group in the benzyl moiety of propafenone molecule changed its potency, efficacy and mechanism of action in the rat aorta. The 4-aminopiridine- and nifedipine sensitive ion channels are involved in mechanism of action of 5-para-methyl and 5-ortho-trifluoromethyl derivate. The introduction of other tested groups in the benzyl moiety does not affect pharmacological properties of the PhPds in relation to propafenone.

Key words

vasodilatation - structure-properties relationship study - ion channels
 

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