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1. DQ-2511 is a new substituted benzamide compound that has gastric prokinetic properties. Actions of the drug on neural discharge in the innervation of the stomach of anaesthetized rats were studied. Standard extracellular methods of multi-unit recording were used to study rates of firing in afferent and efferent filaments teased from gastric branches of the vague nerve. 2. Decreased firing in gastric vagal efferents was associated with increased rates of discharge in the gastric afferents. 3. Intravenous application of DQ-2511 resulted in increased frequency of firing in the efferents in association with decreased rate of discharge in afferent fibres. 4. Application of cholecystokinin octapeptide (CCK8) suppressed activity in the gastric efferents which occurred coincident with the elevated discharge in the afferents. Pretreatment with DQ-2511 blocked the actions of CCK8. 5. The results suggest that the gastric prokinetic action of DQ-2511 may involve suppression of activation of afferents in the sensory component of gastric inhibitory vago-vagal reflex pathways.

We compared the main pharmacological effect of DQ-2511 (3-[[[2-(3,4-dimethoxyphenyl)- ethyl]carbamoyl]methyl]amino-N-methylbenzamide), a novel gastroprokinetic agent, with that of cisapride. Single oral administration of DQ-2511 (3-10 mg kg-1) caused similar significant improvements to delays in gastric emptying of semi-solid meals evoked by cholecystokinin-octapeptide (CCK8: 5 micrograms kg-1, i.v.) in monkeys, to that with cisapride (3 mg kg-1). A 2-week oral treatment of unilaterally vagotomized rats with DQ-2511 (1-10 mg kg-1) lessened delays in gastric emptying, whereas cisapride (0.3-10 mg kg-1) had no effect under the same experimental protocols. In anesthetized rats, bolus intravenous injection of either compound (60 micrograms kg-1) enhanced gastric motility determined by means of strain gauge force transducers. Electrophysiological investigations revealed that bolus injection of DQ-2511 (6-60 micrograms kg-1) depressed the afferent discharge rate of the ventral gastric branch of the vagus nerve, while cisapride showed no effect. These results suggest that the mechanism of ameliorative action of DQ-2511 on delayed gastric emptying may differ from that of cisapride.

The effects of nefiracetam, [N-(2,6-dimethyl-phenyl)-2-(2-oxo-pyrrolidinyl)acetamide, DM-9384], a cyclic derivative of GABA, were investigated in the cycloheximide (CXM)-induced amnesia animal model using the passive avoidance task. Pre-training administration of DM-9384 attenuated the CXM-induced amnesia as indicated by prolongation of step-down latency. It protected against CXM-induced inhibition of choline acetyltransferase activity in the cerebral cortex. These results suggest that DM-9384 attenuates CXM-induced amnesia by interacting with AChergic neuronal system and enhancing protein synthesis in the brain.

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