title: [Anticholinergic effect of 2-aminopyridine and its sulfonylcarbamide derivatives on electromechanical activity in guinea pig atrium].
abstract: The aim of the study was to investigate an action of 2-aminopyridine and its new sulfonylcarbamide derivatives 2-AP21, 2-AP22, 2-AP26, and 2-AP27 (10(-5)-10(-3) M) on carbachol-induced shortening of action potential duration and reduction of contraction force in guinea pig atrial muscles. Experiments were carried out using a standard method of myocardium electromechanical activity registration. Under control conditions (perfusion of atrial strips with Tyrode solution), an average of action potential duration, measured at 90% (AP90) and 50% (AP50) of repolarization, were 112.32+/-6.07 ms and 50.21+/-3.25 ms, (n=19), respectively, and contraction force was of 1.42+/-0.28 mN (n=20). Carbachol (10(-6)M), an agonist of muscarinic acetylcholine receptor and activator of K(Ach) channels, markedly decreased AP90 to 35.31+/-4.21%, AP50--to 26.42+/-2.66% (n=19) (P<0.001), and contraction force--to 24.23+/-2.0% (n=20) (P<0.001) vs. control. Modification of 2-aminopyridine structure by replacing 2-amino group by 4-toluolsulfonylcarbamide fragment and quaternization of nitrogen in pyridine ring increased anticholinergic effect on action potential duration and contraction force. According to their maximal prolongation of AP at 90% of repolarization, all new drugs ranked as follows: 2-AP27>>2-AP26>2-AP22> or =2-AP>2-AP21. 2-aminopyridine derivative 2-AP27, containing 4-toluolsulfonylcarbamide fragment and 4-nitrobenzyl radical at quaternized nitrogen of the pyridine, had the most potent anticholinergic effect on AP90 (936.60+/-178.23%). 2-AP22 and 2-AP26 (containing methyl or allyl radicals at quaternized nitrogen of the pyridine, respectively) showed a much weaker anticholinergic effect (231.39+/-28.48% and 318.25+/-63.81%, respectively). The weakest anticholinergic effect (63.59+/-34.38%) was induced by 2-aminopyridine derivative 2-AP21, which had non-quaternized nitrogen of the pyridine.
authors.affiliation: Institute of Cardiology, Kaunas University of Medicine, Sukileliu 17, 50161 Kaunas, Lithuania. membiof@kmu.lt.
authors.forename: Vida
authors.initials: V
authors.lastname: Gendviliene
authors.forename: Danguole
authors.initials: D
authors.lastname: Zablockaite
authors.forename: Irma
authors.initials: I
authors.lastname: Martisiene
authors.forename: Herta
authors.initials: H
authors.lastname: Gurskaite
authors.forename: Antanas
authors.initials: A
authors.lastname: Stankevicius
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000631:Aminopyridines / Q000494:pharmacology*; D000818:Animals; D016275:Atrial Function / Q000187:drug effects; D002217:Carbachol / Q000494:pharmacology*; D018679:Cholinergic Agonists / Q000494:pharmacology*; D018680:Cholinergic Antagonists / Q000494:pharmacology*; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects*; D007537:Isometric Contraction / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects*; D011976:Receptors, Muscarinic / Q000187:drug effects; D013997:Time Factors
chemical_list: D000631:Aminopyridines; D018679:Cholinergic Agonists; D018680:Cholinergic Antagonists; D011976:Receptors, Muscarinic; D002217:Carbachol; C032439:alpha-aminopyridine