Effects of DQ‐2511 on neutral activity in afferent and efferent loops of gastric vagovagal reflex pathways in the rat

Abstract

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.

Ecabapide, a Novel Gastroprokinetic Agent, Ameliorates Gastric Emptying of Stroke-Prone Spontaneously Hypertensive Rats(SHRSP).

“…The facilitation of gastric emptying involves the sensory component of gastric inhibitory vago-vagal reflex circuits [5,7,13]. The data were supported by the fact that the enhancement of the efferent discharge provoked by ecabapide was completely blocked by bilateral vagotomy.…”

“…The data were supported by the fact that the enhancement of the efferent discharge provoked by ecabapide was completely blocked by bilateral vagotomy. Furthermore, pretreatment with ecabapide completely inhibited the actions of cholecystokinin-octapeptide (CCK8), which suppressed activity in the gastric efferents and simultaneously elevated discharge rates in the afferent nerves [13]. On the other hand, ecabapide was reported to be free of anticholinesterase property and to be devoid of adverse effects including the prolactin release or extrapyramidal reactions [8,9] common to antidopaminergic agents [2,16].…”

Possible Mechanisms Underlying the Suppression of Gastric Vagal Afferents Due to Ecabapide (DQ-2511), a Gastroprokinetic Agent, in Rats.

“…Electro physiological approaches revealed that the drug elicited a facilitatory effect on the gastric efferent activity as a result of a disinhibitory reflex action originating from sup pressed gastric afferents (4). Although the binding affinity of ecabapide to selective receptors has been exhaustively explored, it showed no specific binding (2,5).…”

“…Although the binding affinity of ecabapide to selective receptors has been exhaustively explored, it showed no specific binding (2,5). On the ba sis of the above studies, ecabapide was considered to exert its action via suppression of activation of afferents in the sensory component of gastric inhibitory vago-vagal reflex pathways (3,4). More recently, ecabapide was reported to stimulate the intracellular production of guanosine 3",5' cyclic monophosphate (cGMP) content (5,6) at a con centration as low as 10-' M when rabbit gastric parietal cells were used (7).…”

“…In an additional study using the same dose, L-NNA was administered to rats 1 hr prior to ecabapide treatment. The dosage level of each agent used in the present investigation was selected on the basis of preliminary studies or previously published reports (3,4,11,12). Multi-unit neural discharge in the vagal afferent fibers was recorded extracellularly.…”