Antiarrhythmic and antihypertensive activity of some xanthone derivatives.
Some of appropriate aminoisopropanoloxy derivatives of 4-xanthone were tested for their effect on circulatory system (protection against adrenaline-, barium-, and calcium chloride-induced arrhythmias, as well as hypotensive activity and acute toxicity). The most prominent hypotensive activity was demonstrated by (+/-)-1-[4-(hydroxyethyl)-1-(piperazinyl)]-3-(4-xanthonoxy)-2-propanol dihydrochloride (II), which diminished arterial blood pressure by about 40% during one hour observation. The investigated compounds did not prevent adrenaline- and barium-induced arrhythmias. In calcium-induced model of arrhythmia compound II slightly intensified blocks (about 7%), but delayed extrasystoles (37%), efficiently prevented bigeminy (70%, p <0.01) and diminished (53%, p <0.05) mortality of animals. All investigated compounds decreased heart rate by 10 - 18%, prolonged P-Q section, QRS complex and Q-T interval. The most potent and significant negative chronotropic effect and markedly prolonged duration of P-Q section was demonstrated by compound II. The influence of investigated compounds on ECG components suggests that activity of compound IV is similar to class 1a anti-arrhythmic compounds according to Voughan-Williams classification of antiarrhythmic drugs, because of prolongation of P-Q and Q-T intervals and extension of QRS complex. Compounds II and IV were also evaluated for anticonvulsant activity in the maximal electroshock seizures (MES) and subcutaneous pentylenetetrazole seizure threshold (ScMet) assays and for neurotoxicity (TOX). The anti-MES activity in mice was found for IV, which in a dose of 100 mg/kg within 0.5 h after ip administration showed 75% anticonvulsant protection with 50% neurotoxicity.
Marona
Henryk
H
Department of Technology and Biotechnology of Drugs, Faculty of Pharmacy, Medical College, Jagiellonian University, Kraków, Poland.
Librowski
Tadeusz
T
Cegła
Marek
M
Erdoğan
Cankat
C
Sahin
Nefise Ozlen
NO
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects / Q000138:chemical synthesis / Q000494:pharmacology*; D000927:Anticonvulsants / Q000009:adverse effects / Q000138:chemical synthesis / Q000494:pharmacology; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000138:chemical synthesis / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000188:drug therapy*; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D004562:Electrocardiography; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy; D008297:Male; D051379:Mice; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D023382:Toxicity Tests, Acute; D044004:Xanthones / Q000009:adverse effects / Q000138:chemical synthesis / Q000494:pharmacology*
D000889:Anti-Arrhythmia Agents; D000927:Anticonvulsants; D000959:Antihypertensive Agents; D044004:Xanthones