Pharmacological properties of melochinine, an alkaloid producing Central American cattle paralysis

A Central American cattle paralysis is produced by ingestion of the plant Melochia pyramidata L. (Sterculiaceae). Its main alkaloid "melochinine" has been shown to produce paralysis, bradypnea, bradycardia and hypotension in laboratory animals after p.o., i.p. and i.v. applications. Bradycardia and negative inotropia have been demonstrated in isolated guinea pig atria and paralysis in the isolated phrenic nerve diaphragma preparation as well as in the phrenic nerve in situ preparation with local application. Gas chromatographic measurements suggest a rapid disappearance of melochinine after intravenous application and showed the similarity of the biologically active melochinine concentrations in vivo and in vitro. No unchanged melochinine was found in the urines of mice by thin-layer chromatography. A slight inhibition of the mitochondrial respiration and of some cholinesterases and none of the ATPase was found. Melochinine does not reveal insecticidal activity as does its structural analogue piericidin A, a well known inhibitor of the mitochondrial respiratory chain. The action of the alkaloid may be explained by an unspecific interaction with membranes, partially responsible for a Ca2+-antagonistic effect found in the isolated guinea pig papillary muscle. The proposed non-specific action could be a possible reason for the fact that trials of a specific therapy failed in our experiments.