Antispasmodic effects of an alkaloid extracted from Phyllanthus sellowianus: a comparative study with papaverine.
Infusions of Phyllanthus sellowianus or P. niruri (Euphorbiaceae) are a popular remedy in Brazil for kidney and bladder stones. This study describes the isolation of an alkaloid from P. sellowianus, denoted ALK-1, and compares its antipasmodic activity with that of papaverine on isolated strips of guinea pig ileum and rat uterus, and rat aorta rings. ALK-1 and papaverine promoted a dose-dependent flattening of the dose-response curves obtained to acetylcholine and histamine on ileum strips and of the dose-response curves to acetylcholine and oxytocin on uterine strips. A non-competitive antagonism of noradrenaline-induced contractions by the P. sellowianus alkaloid was also demonstrated on aortic rings. Whereas the antispasmodic potency (pD'2 values) of papaverine did not depend on the muscle preparation and agonist used, ALK-1 exhibited a greater potency on the ileum strips than on the uterine or aortic preparations. Because of this selective antispasmodic action on the ileum, ALK-1 was equipotent to papaverine on this tissue, but was about 10-fold less potent than papaverine on uterine smooth-muscle. The dose-response curves to CaCl2 obtained for potassium-depolarized uterine strips were shifted to the right by both antispasmodics. Similar pA2 values with slopes not differing from unity -1.0 were obtained from Schild plots of the data, suggesting that competitive antagonism of calcium entry into the cell is a mechanism of action common to both alkaloids. The presence of at least one potent antispasmodic alkaloid in P. sellowianus justifies the popular use of infusions of this plant. Smooth muscle relaxation within the urinary or biliary tract probably facilitates the expulsion of kidney or bladder calculi.
D000470:Alkaloids / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D001938:Brazil; D005260:Female; D006168:Guinea Pigs; D007082:Ileum / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000502:physiology; D010208:Papaverine / Q000494:pharmacology*; D010276:Parasympatholytics; D010936:Plant Extracts / Q000494:pharmacology*; D010946:Plants, Medicinal; D051381:Rats; D014599:Uterus / Q000502:physiology
D000470:Alkaloids; D010276:Parasympatholytics; D010936:Plant Extracts; D010208:Papaverine