Actions of alinidine and AQ-A 39 on rate and contractility of guinea pig atria during beta-adrenoceptor stimulation.
We studied two new agents, alinidine (St 567, 2-[N-allyl-N-(2,6-dichlorophenyl)-amino]-2-imidazoline) and AQ-A 39 (5,6-dimethoxy-2-[3[[alpha-(3,4-dimethoxy)-phenylethyl] methylamino]propyl]phthalimidine), in isolated guinea pig atria with respect to their specificity to decrease heart rate but not contractility during beta-adrenoceptor stimulation. Spontaneous electrical activity in sinoatrial node preparations was increased by perfusion with isoprenaline (0.1 micrograms/ml); addition of alinidine (3 micrograms/ml), AQ-A 39 (3 micrograms/ml), or propranolol (0.03-0.3 micrograms/ml) reduced sinus rate to the control values. The same concentrations of these drugs were tested in electrically driven (1 Hz) left atria. The positive inotropic effect of isoprenaline was not affected by alinidine and AQ-A 39; however, it was markedly reduced or abolished by propranolol. The experiments, therefore, demonstrated the bradycardic specificity of alinidine and AQ-A 39 under conditions of beta-adrenoceptor stimulation. A cumulative concentration-response curve for the positive chronotropic effect of isoprenaline was established in spontaneously beating atria. AQ-A 39, 1 and 10 micrograms/ml, reduced the control sinus rate but did not affect the following concentration-response curve of isoprenaline. A similar result was published earlier for alinidine and excludes an interaction of both drugs with isoprenaline on a possible subgroup of selective beta-adrenoceptors in the sinoatrial node.
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002317:Cardiovascular Agents / Q000494:pharmacology*; D003000:Clonidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004594:Electrophysiology; D005260:Female; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects*; D066298:In Vitro Techniques; D054833:Isoindoles; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D010797:Phthalimides / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D012849:Sinoatrial Node / Q000187:drug effects
D000318:Adrenergic beta-Agonists; D002317:Cardiovascular Agents; D054833:Isoindoles; D010797:Phthalimides; D011433:Propranolol; C022192:alinidine; D007545:Isoproterenol; D003000:Clonidine; C030532:falipamil