Electrophysiological characterization of a novel class III antiarrhythmic agent, GLG-V-13 in the mammalian heart.
GLG-V-13, a novel 3,7-diheterabicyclo[3.3.1]nonane, was examined both in vivo and in vitro in order to characterize its electrophysiological, haemodynamic and inotropic properties. Left ventricular epicardial monophasic action potential (MAP), surface ECG and mean arterial blood pressure (MBP) were recorded in six pentobarbital-anaesthetized, artificially ventilated and thoracotomized guinea-pigs. When studied in an intravenous dose interval ranging between 0.5 micrograms/kg and 500 micrograms/kg, GLG-V-13 dose-dependently lengthened the MAP duration (p < 0.05 at doses above 5 micrograms/kg), the atrioventricular conduction time (p < 0.05 at doses above 1 microgram/kg) and the RR interval (p < 0.05 at doses above 25 micrograms/kg). At the highest dose (500 micrograms/kg) these variables were increased by 30%, 13% and 23%, respectively. Only minor effects were noted on intraventricular conduction time (QRS interval) and MBP. In rabbit atrial and papillary muscle preparations, GLG-V-13 (0.32 to 3.2 mg/l) did not exert negative inotropic action. In 10 intact anaesthetized mongrel dogs, left ventricular endocardial MAP at 90% repolarization (MAP90) was measured during atrial pacing before and after administration of GLG-V-13, 3 and 6 mg/kg i.v., respectively.
Fazekas
T
T
Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, USA.
Scherlag
B J
BJ
Carlsson
L
L
Mabo
P
P
Patterson
E
E
Berlin
K D
KD
Lazzara
R
R
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000737:chemistry / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001643:Bridged Bicyclo Compounds / Q000737:chemistry / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D004594:Electrophysiology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D007093:Imidazoles / Q000737:chemistry / Q000494:pharmacology*; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects; D011817:Rabbits
D000889:Anti-Arrhythmia Agents; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D007093:Imidazoles; C095121:GLG-V 13