Subject(s)
Memory/drug effects , Thiazoles/pharmacology , Animals , Avoidance Learning/drug effects , Mice , Quinuclidinyl Benzilate , Radioligand Assay , RatsSubject(s)
Antipsychotic Agents/pharmacology , Fluphenazine/analogs & derivatives , Animals , Antipsychotic Agents/pharmacokinetics , Avoidance Learning/drug effects , Behavior, Animal/drug effects , Dogs , Fluphenazine/pharmacokinetics , Fluphenazine/pharmacology , Hemodynamics/drug effects , Radioimmunoassay , RatsABSTRACT
GYKI-23 107 is a new antiarrhythmic substance with local anaesthetic activity. Its specific pharmacological and cardiovascular effects were studied in vivo and its efficacy was compared with that of lidocaine and mexiletine. GYKI-23 107 was effective against chemically (aconitine and ouabain) induced arrhythmias after both parenteral and oral administration. In aconitine-induced arrhythmia in mice the new compound was more active than either mexiletine or lidocaine after i.p. treatment. In ouabain-induced arrhythmia in dogs, the ED50 of GYKI-23 107 was approximately half that of mexiletine after i.v. injection. GYKI-23 107 and mexiletine produced similar elevation of the fibrillation threshold in anaesthetized cats. After oral pretreatment, GYKI-23 107 showed protective effects against coronary ligation-induced arrhythmia in conscious rats. The circulatory side-effects of GYKI-23 107 in anaesthetized and conscious dogs and cats were milder then those of mexiletine. In the antiarrhythmic dose range there were no adverse cardiovascular actions.
Subject(s)
Anti-Arrhythmia Agents/therapeutic use , Arrhythmias, Cardiac/drug therapy , Propylamines/therapeutic use , Aconitum , Animals , Anti-Arrhythmia Agents/pharmacology , Arrhythmias, Cardiac/chemically induced , Cats , Chemical Phenomena , Chemistry , Dogs , Female , Hemodynamics/drug effects , Lidocaine/therapeutic use , Male , Mexiletine/therapeutic use , Mice , Ouabain , Propylamines/pharmacology , RatsABSTRACT
New, potential aldosterone blocking 17-spiro-oxazolidinone derivatives with androstane, estrane and 13 beta-ethyl-gonane ring system were synthesized. 17S-Spiro-oxiranes were used as starting compounds and the oxazolidinone ring was built up in different ways. All compounds but one were devoid of considerable endocrine activities. 3-Oxo-13 beta-ethyl-gona-4,9(10),11-triene-17S-spiro-5'-(2'-oxo-3'-methyl)oxazolidine shows significant antiandrogen activity on s.c., but none on p.o. administration.
