Cardiodepressor effects of 7-O-demethylisothalicberine, bisbenzylisoquinoline alkaloid isolated from Berberis chilensis.
7-O-demethylisothalicberine (7-O-DI), an alkaloid isolated from Berberis chilensis Gillies ex Hook, induces a negative inotropism and chronotropism on guinea pig isolated atria (IC50 = 1.5 x 10(-4) and 1.8 x 10(-4) M, respectively). As these effects were not antagonized by propranolol, 7-O-DI inhibition of isoproterenol-induced atrial activation seems to be attained through a mechanism distinct of beta-receptor blockade. A probable cholinergic mechanism of action was also ruled out. 7-O-DI atrial effects were completely reversed by a 50% increase of calcium concentration. The spontaneous frequency of rat sinus node was also deeply modified by 7-O-DI, in accordance with previous results obtained in frog cardiac pacemaker cells. It is concluded that 7-O-DI should perform its pharmacological action through calcium entry blockade. These results open expectations for future research about probable therapeutic use for 7-O-DI.
Morales
M A
MA
Departamento de Farmacología, Facultad de Medicina, Universidad de Chile, Santiago.
González
E
E
Torres
R
R
Martínez
J L
JL
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D044182:Benzylisoquinolines; D002121:Calcium Channel Blockers / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007546:Isoquinolines; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D010946:Plants, Medicinal; D051381:Rats; D017208:Rats, Wistar
D000470:Alkaloids; D000889:Anti-Arrhythmia Agents; D044182:Benzylisoquinolines; D002121:Calcium Channel Blockers; D007546:Isoquinolines; C062425:7-O-demethylisothalicberine