Metoclopramide blocks the phenyl diguanide and 5-hydroxytryptamine induced cardiorespiratory reflexes in cats and dogs.

The effects of metoclopramide on the reflex cardiorespiratory responses elicited by stimulation of pulmonary J receptors by right atrial injections of phenyl diguanide (PDG), 5-hydroxytryptamine (5-HT), and capsaicin were investigated in anesthetized spontaneously breathing cats. It was observed that while metoclopramide blocked the responses to PDG and 5-HT injections, it spared the responses to capsaicin injections. Similarly, metoclopramide was without effect on the reflex responses following activation of pulmonary C-fiber receptors (J receptors) by capsaicin in dogs. Reflex cardiorespiratory responses elicited by left atrial injections of PDG and 5-HT, owing to stimulation of cardiac receptors in cats, and reflex responses following right or left atrial injections of PDG and 5-HT, owing to stimulation of aortic chemoreceptors of dogs, were also found to be blocked by metoclopramide. Afferent impulse activity recorded from aortic chemoreceptors of dogs showed that while metoclopramide depressed the excitatory effect of PDG and 5-HT on them, it did not produce any effect on their spontaneous activity and their excitation by hypoxia. The results from the reflex studies show that metoclopramide is capable of antagonizing the reflex responses following the activation of the cardiopulmonary afferents by PDG and 5-HT. Based on the effects on aortic chemoreceptor afferents, it is suggested that PDG, 5-HT, and metoclopramide may be acting upon the regenerative region of the sensory endings.