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

Abstract

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.

C-Fiber Activation Exacerbates Sleep-Disordered Breathing in Rats

“…In the same experimental model of sleep apnea used here, intraperitoneal administration of protoveratrines, which stimulate C-fibers and mechanoreceptors, 2 exacerbated central apnea only during NREM sleep. 19 The present data do not allow us to discriminate the relative importance of vagal and nonvagal C-fiber afferents in CAP-induced exacerbation of sleep apnea. 7 In accordance, administration of a specific 5-HT antagonist blocked serotonininduced increase in REM related apneas 7 and, at a higher dose, reduced REM apnea frequency below control levels.…”

“…2). 18,19 We cannot determine from the present data if apnea expression during NREM sleep may have been a specific effect of C-fiber activation on respiratory pattern generation per se, or if it may have resulted indirectly from an overall reduction in respiratory drive. 2).…”

“…However, the equivalent reductions in specific minute ventilation produced by CAP during NREM and REM sleep argue that the C-fiber afferent system, including afferent vagal input, was being activated by CAP and was being integrated within the brainstem during both NREM and REM sleep. 19 Similarly, metoclopramide was without effect on reflex responses following activation of pulmonary C-fibers by CAP in dogs. 6 In contrast, 5-HT, which does not cross the blood-brain barrier and which primarily acts on 5-HT receptors but also activates many afferent fibers, 3,4,10 produced an increase in spontaneous apnea index only during REM sleep.…”

5‐HT3 receptors

“…Other 5-HT-evoked reflexes thought to be mediated by 5-HT3 receptors include the pulmonary depressor and respiratory chemoreflexes (119)(120)(121) and the cardiogenic hypertensive chemoreflex (122). Other 5-HT-evoked effects that are probably mediated via 5-HT3 receptors on sensory neurones include the pain response to 5-HT administered to a blister base in man (3, 123), the pain response to the subcutaneous administration of carrageenan and formalin in rats (124,125) the wheal and flare response when 5-HT is applied to the human skin (3,126,127) and part of the vasodilation response of the human forearm to 5-HT (128).…”

Phenylbiguanide as electron donor in heterocyclic synthesis

“…Numerous reports have appeared in the literature, describing the cardiovascular reflexes [1][2][3][4][5][6], agonists and antagonists [3][4][5][6][7][8][9], visceral reflexes [10,11], and physiological [12] activity, as well as industrial [13][14][15][16][17] applications of arylbiguanides. Our long-term interest in chemical reactions induced by charge-transfer complexation forms a part of our systematic efforts to obtain new heterocyclic systems [18][19][20][21][22][23][24][25][26][27].…”