HEPATOCELLULAR INJURY WITH DISTINCTIVE MITOCHONDRIAL CHANGES INDUCED BY LERGOTRILE MESYLATE - DOPAMINERGIC ERGOT DERIVATIVE

Abstract

Increased serum activities of the enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) occurred in 12 of 19 patients with idiopathic parkinsonism when they were treated with the ergot derivative lergotrile at an oral dose varying from 50-150 mg daily. Hepatocellular injury was confirmed by microscopic examination of liver biopsies obtained from 3 of these patients when the serum activities of ALT and AST were appreciably elevated. Light microscopy revealed features of mild acute hepatocellular injury, and EM showed proliferation of the smooth endoplasmic reticulum and apparently unique mitochondrial changes in hepatocytes. This is the 1st report of pathological changes in the liver associated with the therapeutic use of an ergot derivative. The presence of a potentially reactive cyanide group in the lergotrile molecule could be causally related to the observed hepatocellular injury. It is suggested that serum ALT and AST activities should be monitored carefully when the therapeutic potential of any new ergot derivative is assessed.