title: The novel potent multidrug resistance inhibitors N,N-bis(cyclohexanol)amine aryl esters are devoid of vascular effects.
abstract: The aim of this study was to investigate the effects of the four isomers (3a, 3b, 3c and 3d) of a novel multidrug resistance-reverting agent - 3,4,5-trimethoxybenzoic acid 4-(methyl-{4-[3-(3,4,5-trimethoxyphenyl)acryloyloxy]cyclohexyl}amino)cyclohexyl ester - on vascular functions in vitro. A comparison of their mechanical and electrophysiological actions in rat aorta rings and single rat tail artery myocytes, respectively, was performed. In rat aorta rings, 3a-d antagonized both 60 mmol/l K(+)- and phenylephrine-induced contraction in a concentration-dependent manner, with maximal relaxation values averaging 50% of controls, 3d being the most effective of the series. The vasorelaxing effect was similar either in presence or absence of intact endothelium. In rat tail artery myocytes, out of the four isomers, only 3a consistently inhibited Ba(2+) current through Ca(v)1.2 channels. Our results provide functional evidence that 3a-d are weak vasorelaxing agents, although at concentrations much higher than those effective for multidrug resistance reversion in cancer cells.
authors.affiliation: Dipartimento di Neuroscienze, Università degli Studi di Siena, Siena, Italy. saponara@unisi.it
authors.forename: Simona
authors.initials: S
authors.lastname: Saponara
authors.forename: Beatrice
authors.initials: B
authors.lastname: Gorelli
authors.forename: Virginia
authors.initials: V
authors.lastname: Tzankova
authors.forename: Cecilia
authors.initials: C
authors.lastname: Martelli
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Teodori
authors.forename: Giampietro
authors.initials: G
authors.lastname: Sgaragli
authors.forename: Fabio
authors.initials: F
authors.lastname: Fusi
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000502:physiology; D001158:Arteries; D002121:Calcium Channel Blockers / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D004952:Esters / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D013623:Tail / Q000098:blood supply; D014664:Vasodilation / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002121:Calcium Channel Blockers; D004952:Esters; D014700:Verapamil