PHARMACOLOGY OF THE GASTRIC PRO-KINETIC DRUG ECABAPIDE (DQ-2511)

The pharmacology of ecabapide (DQ-2511; enyl)ethylcarbamoylmethly]amin o-N-methylbenzamide) is reviewed. Evidence from basic studies in anima l models suggests that the drug acts on peripheral mechanisms of neura l control. In the stomach, ecabapide acts to suppress firing in vagal afferent nerves and thereby reduce the flow of sensory information int o 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 s uppression of activity in the sensory limb of the putative va,oo-vagal reflex pathway. The mechanism of action of ecabapide in suppressing d ischarge in vagal afferent terminals appears to mimic that of nitric o xide by stimulating formation of cGMP and activation of an inhibitory transduction cascade in the sensory fibres. In this respect the mechan ism of its pro-kinetic action differs from other promoter agents. In a ddition to selective actions in the stomach, evidence from electrophys iological studies of enteric neurons in the small intestine suggests t hat 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 inclu de enhanced release of acetylcholine at excitatory synapses and suppre ssion of the release of noradrenaline at inhibitory synapses.