Pharm. Pharmacol. Commun. 2000, 6: 309±312 # 2000 Pharm. Pharmacol. Commun. Received March 8, 2000 Accepted March 28, 2000 Activity of Amaryllidaceae Alkaloids on the Blood Pressure of Normotensive Rats GUILLERMO SCHMEDA-HIRSCHMANN, JAIME A. RODRI Â GUEZ*, JOSE Â I. LOYOLA*, LUIS ASTUDILLO, JAUME BASTIDA { , FRANCESC VILADOMAT { AND CARLES CODINA** Instituto de Quõ Âmica de Recursos Naturales, *Instituto de Biologõ Âa Vegetal y Biotecnologõ Âa, Universidad de Talca, Casilla 747, Talca, Chile and {Universidad de Barcelona, Facultad de Farmacia, Departamento de Productos Naturales, 08028 Barcelona, Catalun Äa, Spain Abstract Plants belonging to the Amaryllidaceae family have been shown to be a good source of biologically active alkaloids. The effect of 20 Amaryllidaceae alkaloids on the blood pressure of normotensive rats was assessed. The compounds evaluated belong to the lycorine, homolycorine, galanthamine, crinane, tazettine and miscellaneous skeletal types. At 15mgkg 1 , eight of the alkaloids assayed showed a signi®cant effect on the arterial pressure of normotensive rats. Seven elicited a hypotensive response >20%, with a lasting time ranging from 20 to 360 min while crinamine showed a hypertensive effect. These ®ndings support the potential of Amaryllidaceae alkaloids as hypotensive drugs. The Amaryllidaceae plant family has been shown to be a rich source of alkaloids with promising biological activity, such as cytotoxic, antimalarial, antiproliferative, antiapoptotic and hypotensive effects (Likhitwitayawuid et al 1993; Desai et al 1998; Mok et al 1998; Taesotikul et al 1998). Lycorine and 1,2-di-O-acetyllycorine exhibit cyto- toxic and antimalarial activity (Campbell et al 1998). Lycorine also showed an inhibitory effect on calprotectin-induced apoptosis (Mikami et al 1999). Galanthamine has been studied as a possible therapeutic agent in Alzheimer's disease because of its inhibitory effect on acetylcholinesterase (Harvey 1995). The antiproliferative and antimalarial effects of Amaryllidaceae alkaloids have been previously reported (Gabrielsen et al 1992; Weniger et al 1995). In an attempt to expand knowledge on the bio- logical activity of Amaryllidaceae alkaloids, we studied the cardiovascular effects of 20 alkaloids on the blood pressure of normotensive rats. Materials and Methods Alkaloids The alkaloids used in this study were isolated from several Amaryllidaceae species as previously described (Viladomat et al 1995; Bastida et al 1998). The purity of the tested compounds was assessed by the micromelting point, thin layer chromatography and 1 H NMR spectroscopy. The spectroscopically pure free bases were treated with HCl to obtain the corresponding hydrochlorides. The water-soluble chlorhydrates were used for the tests. The structures of the assayed compounds are shown in Figure 1. Animals Male adult Sprague-Dawley rats, 200±250g, were used. Rats were housed at a constant temperature of 22  C with a 12±h light±dark photoperiod and had free access to food and water. Testing was carried out during the light period of the cycle. Hypotensive effect in normotensive rats To assess the cardiovascular effects of alkaloids, doses ranging from 02 to 10mgkg 1 are com- monly used (Mok et al 1998). Rats were anaes- thetized with urethane (12gkg 1 , i.p.). The blood pressure (BP) was measured via a catheter implanted into the left carotid artery and connected to a P-23 XL Gilson pressure transducer. Alkaloids, as HCl salts, were dissolved in saline solution and administered intravenously through the femoral vein at a dose of 15mgkg 1 in 01mL. Correspondence: G. Schmeda-Hirschmann, Instituto de Quõ Â- mica de Recursos Naturales, Universidad de Talca, Casilla 747, Talca, Chile. E-mail: schmeda@pehuenche.utalca.cl