Heinz body hemolytic anemia induced by DQ-2511, a new anti-ulcer drug, in dogs

Drug Safety Research Center, Developmental Research Laboratories, Daiichi Pharmaceutical Company Ltd., Tokyo R & D Center, Japan.
Fundamental and Applied Toxicology 03/1993; 20(2):141-6. DOI: 10.1006/faat.1993.1019
Source: PubMed

ABSTRACT DQ-2511, a new anti-ulcer drug, was administered to beagle dogs for 4 weeks to investigate the mechanism whereby this drug induced hemolytic anemia and its reversibility in comparison with beta-acetylphenylhydrazine. Hemolytic anemia accompanied by an increase in the number of cells containing Heinz bodies that was preceded by a marked decrease in blood-reduced glutathione concentration was observed in dogs receiving 600 mg/kg of DQ-2511, but only a slight increase in the methemoglobin level was noted. beta-Acetylphenylhydrazine, however, caused hemolytic anemia accompanied by marked increases in both Heinz body-containing cells and methemoglobin concentration, but the blood-reduced glutathione concentration was not decreased consistently with the formation of Heinz bodies. Hemolytic anemia disappeared after a 4-week recovery period in the dogs that received DQ-2511. These results suggest that decreases in reduced glutathione in erythrocytes play an important role in the anemia and Heinz body formation induced by DQ-2511, but not by beta-acetylphenylhydrazine.

  • [Show abstract] [Hide abstract]
    ABSTRACT: The pharmacology of ecabapide (DQ-2511; 3-[2-(3,4-dimethoxyphenyl)ethylcarbamoylmethyl]amino-N-methylbe nzamide) is reviewed. Evidence from basic studies in animal models suggests that the drug acts on peripheral mechanisms of neural control. In the stomach, ecabapide acts to suppress firing in vagal afferent nerves and thereby reduce the flow of sensory information into the dorsal vagal complex. The enhancement of the efferent discharge provoked by ecabapide was completely blocked by bilateral vagotomy, as suggested by increased firing in vagal efferent fibres, preceded by suppression of activity in the sensory limb of the putative vago-vagal reflex pathway. The mechanism of action of ecabapide in suppressing discharge in vagal afferent terminals appears to mimic that of nitric oxide by stimulating formation of cGMP and activation of an inhibitory transduction cascade in the sensory fibres. In this respect the mechanism of its pro-kinetic action differs from other promoter agents. In addition to selective actions in the stomach, evidence from electrophysiological studies of enteric neurons in the small intestine suggests that ecabapide might have actions similar to those of other substituted benzamides on synaptic transmission in the intramural nervous system of this specialized region of the digestive tract. These actions include enhanced release of acetylcholine at excitatory synapses and suppression of the release of noradrenaline at inhibitory synapses.
    Journal of Pharmacy and Pharmacology 01/1998; 49(12):1168-74. DOI:10.1111/j.2042-7158.1997.tb06064.x · 2.16 Impact Factor