Characterization of NGP 1-01, an aromatic polycyclic amine, as a calcium antagonist.
Primary pharmacological and electrophysiological screening procedures were carried out on the aromatic polycyclic amine 3-hydroxy-4-benzyl-4-azahexacyclo[5.4.1.0(2,6).0(3,10).0(5,9).0(8, 11]- dodecane (NGP 1-01). Effects observed in the isolated guinea-pig atria and ileum were, respectively, reversal of CaCl2 induced positive chronotropy and inotropy and papaverine-like depression of the dose-response curve induced by acetyl choline. Electrophysiological studies using isolated guinea-pig papillary muscle showed a reduction in the action potential (AP) plateau potential and an increase in AP duration with accompanying negative inotropic effects. The calcium-mediated (slow response) AP was completely, but reversibly blocked by NGP 1-01 at concentrations of 5 X 10(-5) M and higher. Experiments on sheep Purkinje fibres strongly supported the finding that NGP 1-01 blocks the slow inward (calcium dependent) current Isi, but also suggested a decrease brought about in an outward current, most probably the background potassium current, IK1.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001681:Biological Assay; D001952:Bridged-Ring Compounds / Q000494:pharmacology* / Q000633:toxicity; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000633:toxicity; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007928:Lethal Dose 50; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D012756:Sheep; D013329:Structure-Activity Relationship
D001952:Bridged-Ring Compounds; D002121:Calcium Channel Blockers; C049649:NGP 1-01