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  • Title: Hypotensive and antiarrhythmic effects of a new alkaloid, the 13-hydroxylupanine-2-pyrrolcarbonic acid ester, from the Madagascan plant Cadia ellisiana.
    Author: Lindner E, Kaiser J, Schacht U.
    Journal: Arzneimittelforschung; 1976; 26(9):1651-7. PubMed ID: 11808.
    Abstract:
    The alkaloid 13-hydroxylupanine-2-pyrrolcarbonic acid ester (Hoe 933) from the Madagascan plant Cadia ellisiana has an hypotensive and antiarrhythmic effect. The hypotensive effect in dogs, monkeys, and rats anaesthetized with barbiturates reaches its maximum with 0.2 mg/kg i.v. However, the hypotensive effect is much weaker in conscious animals. The enteral absorption in the dog is good; an intraduodenal dose of only 0.5 mg/kg lowered the blood pressure. In the isolated rabbit heart whose accelerator nerves were intact, the perfusion with concentrations of 0.6 mug/min Hoe 933 (total dose 6 mug) decreased the release of norepinephrine from the nerve endings, reduced the positive inotropic effect, and diminished the increase in heart rate produced by electrical stimulation of the accelerator nerve. The effect of the stimulation of the accelerator nerve on dp/dt in dogs in situ was considerably diminished by such low doses as 10 and 25 mug/kg i.v. Consequently, the alkaloid inhibits sympathetic impulse transmission. Sympathetic circulatory reflexes are weakened by the compound. The alkaloid has also a ganglionic blocking effect, which is demonstrated on the upper cervical ganglion of the cat. The effect of preganglionic stimulation of the nictitating membrane was reduced with 200 mug Hoe 933/kg i.v. In the isolated guinea pig heart the effect of nicotine on heart rate and contraction was diminished. In this respect the ganglion blocker pentolinium is 8 times more active. The antifibrillatory effect of Hoe 933 was demonstrated with 0.3 mg/kg i.v. in supercooled cats, the antiarrhythmic activity was evident with 0.5 mg/kg i.v. in dogs intoxicated with K-strophanthin. In isolated hearts of guinea pigs, a dose of only 6 mug/heart inhibited ventricular fibrillation induced by aconitine and digitoxin. Even the toxicity of digoxin was diminished by previous administration of 300 mug/kg i.v. The relative refractory period and the duration of the action potential were prolonged in the isolated papillary muscle of the guinea pig heart.
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