Assuntos
Antipsicóticos/farmacologia , Flufenazina/análogos & derivados , Animais , Antipsicóticos/farmacocinética , Aprendizagem da Esquiva/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Cães , Flufenazina/farmacocinética , Flufenazina/farmacologia , Hemodinâmica/efeitos dos fármacos , Radioimunoensaio , RatosRESUMO
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.
Assuntos
Antiarrítmicos/uso terapêutico , Arritmias Cardíacas/tratamento farmacológico , Propilaminas/uso terapêutico , Aconitum , Animais , Antiarrítmicos/farmacologia , Arritmias Cardíacas/induzido quimicamente , Gatos , Fenômenos Químicos , Química , Cães , Feminino , Hemodinâmica/efeitos dos fármacos , Lidocaína/uso terapêutico , Masculino , Mexiletina/uso terapêutico , Camundongos , Ouabaína , Propilaminas/farmacologia , RatosRESUMO
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.