Antioquine: a new bisbenzylisoquinoleine alkaloid with calcium antagonist activity.
The objective of this work was to examine the smooth muscle relaxing properties of antioquine, compared to papaverine, in isolated rat uterus. The results obtained show that both antioquine and papaverine are capable of relaxing sustained contractions induced by Ca2+ in K-depolarizing solution as well as the spontaneous activity of rat uterus. Antioquine (0.1 mM, 0.5 mM and 1 mM) also induces a displacement to the right of the dose-response curves to Ca2+, and the antagonism was not competitive. Papaverine produced a decrease in the frequency and amplitude of contractile responses induced by oxytocin, and these inhibitory effects were observed regardless of whether papaverine was added before or after the induced contractions. On the other hand, antioquine only modified the frequency of contractile responses to oxytocin or desynchronized cumulative dose-response curves to oxytocin when the uterus was preincubated with this alkaloid before addition of the agonist. These experiments suggest that the relaxant effects produced by antioquine may be due to the blockade of calcium movements across the cell membrane, mainly through voltage-operated channels, whereas papaverine affects Ca2+-entry both through VOCs and through ROCs.
D'Ocon
M P
MP
Laboratorio de Farmacognosia y Farmacodinamia, Facultad de Farmacia, Valencia, Spain.
Candenas
M L
ML
Anselmi
E
E
Zafra-Polo
M C
MC
Cortes
D
D
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D044182:Benzylisoquinolines; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002122:Calcium Chloride / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D010121:Oxytocin / Q000494:pharmacology; D010208:Papaverine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014590:Uterine Contraction / Q000187:drug effects
D000470:Alkaloids; D044182:Benzylisoquinolines; D002121:Calcium Channel Blockers; D010121:Oxytocin; C059733:antioquine; D010208:Papaverine; D002122:Calcium Chloride; D011188:Potassium