Calcium antagonist properties of the bisbenzylisoquinoline alkaloid cycleanine.
The alkaloid cycleanine ([12aR-(12aR,24aR)]-2,3,12a,13,14,15,24,24a-octa hydro-5,6,17,18- tetramethoxy-1,13-dimethyl-8, 11:20,23-dietheno-1H,12H [1,10]dioxacyclooctadecino[2,3,4-ij:11,12,13-i'j']diisoquinolin e) was extracted from the bulbs of Stephania glabra (Roxb) Miers and its effects on cardiac and smooth muscle preparations were studied and compared to those of nifedipine (1,4-dihydro-2, 6-dimethyl-4-(2-nitrophenyl)-3,5-pyridine dicarboxylic acid dimethylesther). Cycleanine inhibited the KCl-induced contraction of rabbit aortic rings with higher potency than nifedipine. IC50s for cycleanine and nifedipine were 0.8 and 7.10(-9) M respectively. Cycleanine had minor effects on the norepinephrine-induced contraction of rabbit aortic rings. Cycleanine and nifedipine also depressed the contraction of rat ventricular preparations but with lower potency (IC50 = 3 and 0.03.10(-6) M respectively). Action potential duration of rat right ventricular strips was decreased by both compounds. L-type Ca-current (ICaL) of single rat ventricular cardiomyocytes was inhibited by cycleanine in a voltage- and frequency-dependent manner. With a higher potency nifedipine inhibited ICaL in a tonic and almost frequency-independent manner. The results suggest that cycleanine can act as a potent vascular selective Ca-antagonist.
Martínez
J A
JA
Laboratorio de Electrofisiología, Instituto de Cardiología y Cirugía Cardiovascular, La Habana, Cuba.
Bello
A
A
Rubio
L L
LL
Rodríguez
C
C
Galán
L
L
Caudales
E
E
Alvarez
J L
JL
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004558:Electric Stimulation; D006352:Heart Ventricles / Q000187:drug effects; D066298:In Vitro Techniques; D007546:Isoquinolines; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009200:Myocardial Contraction / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011817:Rabbits; D051381:Rats
D000470:Alkaloids; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004365:Drugs, Chinese Herbal; D007546:Isoquinolines; C037098:cycleanine; D009543:Nifedipine