Pharmacology of the gastric pro-kinetic drug ecabapide (DQ-2511).

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.