title: The novel phenylpropiophenone derivates induced relaxation of isolated rat aorta.
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.
authors.affiliation: Department of Pharmaceutical Chemistry, University of Belgrade, Belgrade, Serbia. blucic@pharmacy.bg.ac.rs
authors.forename: B
authors.initials: B
authors.lastname: Ivković
authors.forename: S
authors.initials: S
authors.lastname: Vladimirov
authors.forename: R
authors.initials: R
authors.lastname: Novaković
authors.forename: V
authors.initials: V
authors.lastname: Cupić
authors.forename: H
authors.initials: H
authors.lastname: Heinle
authors.forename: L
authors.initials: L
authors.lastname: Gojković-Bukarica
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008012:Lidocaine / Q000494:pharmacology; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011405:Propafenone / Q000494:pharmacology; D011427:Propiophenones / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D011427:Propiophenones; D010656:Phenylephrine; D011405:Propafenone; D008012:Lidocaine; D009543:Nifedipine