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PubMed1992

Effects of sympathetic stimulation on use dependence of lidocaine, mexiletine, and quinidine in an intact canine model.

The use- or rate-dependent effects of a continuous infusion of lidocaine (n = 6, serum level 3.1 +/- 0.34 micrograms/mL), mexiletine (n = 8, serum level 7.08 +/- 0.90 micrograms/mL), and quinidine (n = 6, serum level 6.8 +/- 1.22 micrograms/mL) were studied in an open chest canine preparation. A use-dependent effect on conduction was assessed by measuring the change in the His to surface ventricular activation (HV) time at differing atrial paced rates during drug infusion. Global sympathetic activation was achieved by nondecentralized left stellate ganglion stimulation (4-10 Hz, 6-12 V, 2 ms) and use dependence at the same cycle lengths was compared. Repolarization times were measured from epicardial monophasic action potentials recorded from the anterior left ventricle throughout the study. There was no significant change in the HV time during control studies with or without left stellate stimulation. Use-dependent slowing of conduction was seen in all studies during drug infusion. This was evident at cycle lengths of 300-190 ms for quinidine and at cycle lengths less than 250 ms for lidocaine and mexiletine. Stellate stimulation attenuated use dependence in all studies. This effect was significant from cycle lengths of 300-190 ms for lidocaine and quinidine and at cycle lengths shorter than 230 ms for mexiletine (p less than 0.05). Stellate stimulation significantly reduced use-dependent prolongation of the HV interval by an average of 60%. During stellate stimulation there was a nonsignificant trend towards cycle length independent shortening of action potential duration both at baseline and in the presence of drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

PubMed1983

Dual mechanism for catecholamine secretion in the dogfish shark Squalus acanthias.

Both 1,1-dimethyl-4-phenylpiperazinium iodide, a ganglionic stimulating drug (DMPP), and potassium ion (K+) cause a pressor response when injected into Squalus acanthias, an elasmobranch. The pressor responses are due to increased secretion of epinephrine and norepinephrine. The pressor response to DMPP can be blocked by prior infusion of hexamethonium, a ganglionic blocking drug. However, ganglionic blockade does not inhibit the pressor response to K+. Plasma catecholamine concentrations do not increase significantly in response to challenge with DMPP after hexamethonium infusion, but exceedingly high levels of plasma catecholamines quickly appear after K+ injection following hexamethonium infusion. It is concluded that there are at least two mechanisms controlling catecholamine secretion in the dogfish, one of which involves the ganglion cells that are intimately associated with chromaffin cells in the chromophil bodies that are so characteristic of this species and elasmobranchs in general.

Animals↗

PubMed1978

Ganglionic action of some newly synthesized glutarimide compounds.

20 newly synthesized glutarimide compounds and their organic bases were investigated for their action on the autonomic ganglion in cats. Compounds 1 to 7 having piperidine moiety showed mainly ganglionic stimulant activity as evidenced by rise in blood pressure, contraction of nictitating membrane and rise in urinary bladder pressure of cats, which was completely blocked by C6 and partly by atropine. Compound 8 and 9 having diethylamine moiety showed initial stimulation--followed by blockade of the autonomic ganglia. Compounds 10 to 13 having morpholine moiety showed stimulation of both sympathetic and parasympathetic autonomic nervous system. The responses were due to effect partly on ganglia and partly on the receptors. Compounds 14 to 20, which have alkyl substitution chain at position 4 of beta-carbon atom, showed depressor action. The ganglionic activity of the glutarimide compounds in various groups was found to be in inverse ratio to the length of the alkyl side chain at position 4 of the beta-carbon atom.

Animals↗

PubMed2001

Selective AV nodal vagal stimulation improves hemodynamics during acute atrial fibrillation in dogs.

Although the atrioventricular node (AVN) plays a vital role in blocking many of the atrial impulses from reaching the ventricles during atrial fibrillation (AF), a rapid irregular ventricular rate nevertheless persists. The goals of the present study were to explore the feasibility of novel epicardial selective vagal nerve stimulation for slowing of the ventricular rate during AF and to characterize the hemodynamic benefits in vivo. Electrophysiological-echocardiographic experiments were performed on 11 anesthetized open-chest dogs. Hemodynamic measurements were performed during three distinct periods: 1) sinus rate, 2) AF, and 3) AF with vagal nerve stimulation. AF was associated with significant deterioration of all measured parameters (P < 0.025). The vagal nerve stimulation produced slowing of the ventricular rate, significant reversal of the pressure and contractile indexes (P < 0.025), and a sharp reduction in one-half of the abortive ventricular contractions. The present study provides comprehensive evidence that slowing of the ventricular rate during AF by selective ganglionic stimulation of the vagal nerves that innervate the AVN successfully improved the hemodynamic responses.

Acute Disease↗

PubMed1991

CP-93,129, a potent and selective 5-HT1B receptor agonist blocks neurogenic plasma extravasation within rat but not guinea-pig dura mater.

Pretreatment with CP-93,129 blocked plasma extravasation in rat dura mater induced by electrical trigeminal ganglion stimulation when administered at greater than or equal to 140 nmol kg-1, i.v. but did not affect plasma leakage in guinea-pig at 460 or 1400 nmol kg-1. Sumatriptan, a 5-HT1D-like receptor agonist, blocked plasma extravasation in the guinea-pig model when administered at 7 nmol kg-1. In as much as CP-93,129 binds with micromolar affinities to 5-HT1A, 5-HT1C, 5-HT1D, and 5-HT2 recognition sites, and with nanomolar affinity to the 5-HT1B receptor subtype, blockade of plasma extravasation in the rat dura mater may be mediated by 5-HT1B receptors whereas the 5-HT1D receptor may be more relevant to the guinea-pig.

Animals↗

PubMed1978

Direct evidence of acetylcholine releasing effect of serotonin in the Auerbach plexus.

The mode of action of serotonin on isolated longitudinal muscle strip with attached Auerbach plexus and on whole ileum preparation has been studied. Atropine, tetrodoxtoxin, morphine and alpha-adrenoceptor stimulants inhibited the contractions of the strips and whole ileum in response to serotonin. In the presence of atropine (2 X 10(-8) M) at 9 times higher concentration of serotonin was needed to produce the same contraction of the ileum as in control experiments. These facts indicate that the contractile effect of serotonin on the longitudinal muscle of ileum might be mediated via a cholinergic pathway. Direct evidence has also been provided that serotonin is capable of releasing acetylcholine from the Auerbach plexus. It is very likely that serotonin stimulates ganglion cells, which in fact leads to firing and, consequently, to an increase of acetylcholine release from the nerve terminals.

Acetylcholine↗

PubMed1964

ANGIOTENSIN AND PERIPHERAL SYMPATHETIC NERVE ACTIVITY.

On the isolated vas deferens of the guinea-pig angiotensin potentiated strongly the height of contractions due to electrical stimulation of the hypogastric nerve; it did not affect the responses to noradrenaline and acetylcholine, nor did it elicit any contraction when given alone. Angiotensin likewise potentiated the responses of the cat spleen to nerve stimulation, but it also induced by itself strong contractions of the organ and reduction of the venous outflow. In experiments on the arterial blood pressure of anaesthetized and spinal cats, in which sympathetic postganglionic transmission was temporarily blocked by nicotine or tetramethylammonium, pressor responses to angiotensin were strongly reduced. As with some ganglion-stimulating drugs, the pressor responses, enhanced after a second series of nicotine injections, were reduced to the control level by hexamethonium. These findings indicate the involvement of peripheral sympathetic nerves in the action of angiotensin: the hypothesis is advanced that angiotensin acts at the peripheral nerve endings by promoting a greater output of noradrenaline.

Acetylcholine↗

PubMed1992

5-Hydroxytryptamine receptor agonists for the abortive treatment of vascular headaches block mast cell, endothelial and platelet activation within the rat dura mater after trigeminal stimulation.

Antidromic stimulation of small caliber trigeminal axons causes neurogenic inflammation in the dura mater and tongue as evidenced by marked increases in mast cell activation, protein extravasation, as well as in the numbers of endothelial cytoplasmic vesicles, endothelial microvilli and platelet aggregates within ipsilateral post-capillary venules. In this report, we examined the effects of pretreatment with serotonin1 receptor agonists, dihydroergotamine (50 micrograms/kg, i.v.) and sumatriptan (100 micrograms/kg, i.v.) on the light and electron microscopic changes which develop after trigeminal ganglion stimulation. Both dihydroergotamine and sumatriptan are useful in the acute treatment of vascular headaches and bind with high affinity to 5-HT1D receptors. Both drugs decreased significantly the number of dural vessels showing endothelial or platelet changes and the numbers of activated mast cells, but did not affect the neurogenic response in the tongue. The drugs also blocked the accumulation of horseradish peroxidase reaction product within the endothelium and perivascular space on the stimulated side. The receptor is not present on trigeminovascular fibers innervating extracranial cephalic tissues. Drug mechanism probably involves inhibition of a proximal step in the pathophysiological cascade (e.g., via activation of a prejunctional receptor) because (a) receptors for sumatriptan have not been identified on mast cells whereas the inflammatory response was attenuated in mast cells as well as within platelets and the endothelium and (b) previous work indicates that sumatriptan and dihydroergotamine block neurotransmitter release. Hence, constriction of vascular smooth muscle mediated by postjunctional 5-hydroxytryptamine receptors is unlikely to explain the anti-inflammatory actions of dihydroergotamine or sumatriptan reported here.

Animals↗

PubMed1992

Norepinephrine and alpha-2 adrenoceptors modulate active ion transport in porcine small intestine.

The effects of norepinephrine (NE) were examined on active ion transport in the porcine distal jejunum under base-line conditions and after electrical transmural stimulation (ETS). Serosal administration of NE decreased basal short-circuit current across sheets of muscle-stripped jejunal submucosa-mucosa in vitro. These effects were absent in tissues pretreated with the neuronal conduction blocker, tetrodotoxin. NE stimulated net Na secretion in tissues which displayed basal net Na and Cl absorption and increased net Cl absorption in tissues which displayed net Na absorption and Cl secretion under base-line conditions. Moreover, NE inhibited short-circuit current elevations produced by ETS (300 pulses at 10 Hz, 0.5 msec pulse duration, 2.8 mA cm-2), the ganglionic stimulant dimethylphenyl-piperazinium or the gut peptide neurotensin. In contrast, NE did not alter mucosal responses to the directly acting secretagogues forskolin and carbachol. The inhibitory action of NE on mucosal responses evoked by ETS were selectively antagonized by the alpha adrenoceptor blockers phentolamine and yohimbine. Moreover, the selective alpha-2 adrenoceptor agonists p-aminoclonidine, UK-14,304 and oxymetazoline and the NE releasing agent tyramine mimicked the inhibitory effects of NE on ETS-evoked mucosal responses. Desipramine, a blocker of neuronal NE uptake, produced a 1000-fold increase in the potency of NE at concentrations less than 1 nM. These results suggest that NE modulates active ion transport by interacting with alpha-2 adrenoceptors located on submucosal neurons of the porcine small intestine.

Adrenergic alpha-Agonists↗

PubMed2002

Epinephrine in the heart: uptake and release, but no facilitation of norepinephrine release.

BACKGROUND: Several studies have suggested that epinephrine augments the release of norepinephrine from sympathetic nerve terminals through stimulation of presynaptic receptors, but evidence pertaining to this mechanism in the heart is scarce and conflicting. Using the microdialysis technique in the porcine heart, we investigated whether epinephrine, taken up by and released from cardiac sympathetic nerves, can increase norepinephrine concentrations in myocardial interstitial fluid (NE(MIF)) under basal conditions and during sympathetic activation. METHODS AND RESULTS: During intracoronary epinephrine infusion of 10, 50, and 100 ng/kg per minute under basal conditions, large increments in interstitial (from 0.31+/-0.05 up to 140+/-30 nmol/L) and coronary venous (from 0.16+/-0.08 up to 228+/-39 nmol/L) epinephrine concentrations were found, but NE(MIF) did not change. Left stellate ganglion stimulation increased NE(MIF) from 3.4+/-0.5 to 8.2+/-1.5 nmol/L, but again, this increase was not enhanced by concomitant intracoronary epinephrine infusion. Intracoronary infusion of tyramine resulted in a negligible increase in epinephrine concentration in myocardial interstitial fluid (EPI(MIF)), whereas 30 minutes after infusion of epinephrine an increase of 9.5 nmol/L in EPI(MIF) was observed, indicating that epinephrine is taken up by and released from cardiac sympathetic neurons. Although 68% to 78% of infused epinephrine was extracted over the heart, the ratio of interstitial to arterial epinephrine concentrations was only approximately 20%, increasing to 29% with neuronal reuptake inhibition. CONCLUSIONS: Our findings demonstrate epinephrine release from cardiac sympathetic neurons, but they do not provide evidence that epinephrine augments cardiac sympathoneural norepinephrine release under basal conditions or during sympathetic activation.

Adrenergic Uptake Inhibitors↗

PubMed1983

Arecoline induced nicotinic and muscarinic stimulation of the superior cervical ganglion of cat.

Arecoline (10-500 micrograms) stimulated the superior cervical ganglion (s.c.g.) of cat following intra-arterial injection into the ganglion. The ganglion stimulating effect of arecoline was weaker than that of dimethylphenylpiperizinium (DMPP) but stronger than that of pilocarpine. Similarly, the time course of response to arecoline was slower than that of DMPP but faster than that of pilocarpine. The gangliomimetic effects of arecoline, nicotine and DMPP are prevented by hexamethonium, tetraethylammonium and high doses of nicotine and arecoline. Eserine potentiated the response to arecoline but not that to DMPP and nicotine. Response to submaximal preganglionic stimulation and KCl were potentiated by arecoline and pilocarpine but not by DMPP and nicotine. The responses to arecoline and pilocarpine were also prevented by atropine which did not alter the responses to DMPP and nicotine. It is suggested that arecoline stimulated the muscarinic as well as nicotinic receptors in the s.c.g. of cat and that acetylcholine is likely to be involved partially in the gangliomimetic effects of arecoline.

Animals↗

PubMed1997

Chronic electrical stimulation of the gasserian ganglion for the relief of pain in a series of 34 patients.

The use of an implanted system for chronic electrical stimulation of the gasserian ganglion for relief of facial pain was described in 1980 by Meyerson and Håkansson. Between 1982 and 1995, the senior author (R.R.T.) performed gasserian ganglion stimulation in 34 patients for the relief of chronic medically intractable facial pain. The etiology of pain was peripheral damage to the trigeminal nerve in 22 patients (65%), central (stroke) damage in seven (21%), postherpetic neuralgia in four (12%), and unclassifiable cause in one (3%). All patients received a trial of transcutaneous stimulation (Stage 1). Successful trials in 19 patients (56%) were followed by implantation of a permanent system (Stage II). Trial and postimplantation stimulation were deemed successful when there was a reduction of pain by at least 50% whenever the stimulator was on. Success rates varied from five (71%) of seven patients for central pain to five (23%) of 22 for peripheral pain and none (0%) of four for postherpetic neuralgia. The median follow-up duration in successful cases was 22.5 months. Infections occurred in seven patients, all of whom had undergone Stage II treatment. Infections were more frequent when the stimulating electrode from Stage I was left in place for Stage II (six [43%] of 14) than when completely new hardware was used and prophylactic antibiotic drugs were administered (one [20%] of five). Other complications included iatrogenic injury to the trigeminal nerve or ganglion in three cases (9%), transient diplopia in two (6%), increased pain in two (6%), and various technical problems in 10 (29%). It is concluded that pain of central origin (stroke) is the type most likely to be relieved by this procedure. This finding is new, as the few other clinical series reported to date contain no patients with this type of pain. The risk of infection seems to be lower when completely new hardware is used for Stage II and prophylactic antibiotic drugs are administered.

Antibiotic Prophylaxis↗

PubMed1992

The trigemino-vascular system and migraine.

Neurogenic inflammation has been proposed as a possible pathogenetic mechanism for migraine and cluster headache. Antidromic stimulation of trigeminal fibers causes plasma protein extravasation, mast cell activation and degranulation, vacuolation and increase in endothelial vesicle number within post capillary venules in rat dura mater. The antimigraine drugs sumatriptan and dihydroergotamine block the development of plasma extravasation and ultrastructural changes, as well as plasma calcitonin gene-related peptide (CGRP) increase in the superior sagittal sinus following electrical trigeminal ganglion stimulation. Sumatriptan and dihydroergotamine bind with high affinity to the 5-HT1D/1B receptors, thus suggesting that their neurogenic antiinflammatory activity is mediated by activation of 5-HT autoreceptors present on sensory fibers innervating blood vessels in dura mater.

Blood Proteins↗

PubMed1995

Neural control of mouse small intestinal longitudinal muscle: interactions with inflammatory mediators.

The present study was undertaken to investigate neural control of mouse small intestinal longitudinal muscle. Electrical field stimulation evoked acetylcholine- and neurokinin A-mediated contractile responses, whereas nitric oxide-mediated neurotransmission resulted in relaxation. The inflammatory mediators, histamine and leukotriene D4, contracted the longitudinal muscle preparation. Histamine-evoked contractions resulted from binding to histamine H1 receptors on non-neural cells of the small intestine. Leukotriene D4 played a role in neurokinin A-mediated excitation as the leukotriene D4 receptor antagonist, WY 48,252, reduced the response to nerve stimulation under noncholinergic conditions by almost 80%. In contrast, WY 48,252 had no effect on the response to exogenous neurokinin A, indicating that the response to this neurotransmitter is not mediated by leukotriene D4 release. Subthreshold concentrations of leukotriene D4 did not modify the response to neurokinin A, ruling out a synergistic relationship between these two agonists. Leukotriene D4 did not cause synaptic transmitter release through ganglionic stimulation, because its contractile effect was tetrodotoxin insensitive, and did not contribute to noncholinergic excitation through stimulation of neurokinin A release, as the neurokinin2 receptor antagonist, MEN 10,376, did not alter the response to leukotriene D4. Instead leukotriene D4 may modulate the release of neurokinin A from nerve endings during nerve stimulation.

Amino Acid Sequence↗

PubMed1993

Dispersion of refractoriness in normal and ischaemic canine ventricle: effects of sympathetic stimulation.

OBJECTIVE: Dispersion in refractoriness is considered a major factor in induction and persistence of cardiac arrhythmias. The sympathetic nervous system is known to modulate refractoriness. An index of refractoriness has therefore been assessed in normal and ischaemic myocardium simultaneously at multiple sites, with and without sympathetic stimulation. METHODS: In six dogs on total cardiopulmonary bypass the average interval between local activations was measured during artificially induced ventricular fibrillation from extracellular electrograms simultaneously recorded from 32 ventricular sites. These local ventricular fibrillation intervals may be used as an index of local refractoriness. RESULTS: During regional ischaemia, ventricular fibrillation intervals of ischaemic sites could prolong by up to 60% after 3 min following coronary occlusion. Left stellate ganglion stimulation during ischaemia produced either no response or prolonged the ventricular fibrillation intervals even further at ischaemic sites, whereas ventricular fibrillation intervals at non-ischaemic sites shortened. Dispersion in refractoriness across the ischaemic border increased by 14-59% in individual hearts following sympathetic stimulation during acute, regional ischaemia. CONCLUSIONS: Due to opposite effects on normal and ischaemic myocardium, sympathetic stimulation increases the difference in refractoriness over the ischaemic border. This may enhance the chance for regional conduction block and the propensity to re-entrant arrhythmias.

Acute Disease↗

PubMed1973

An inhibition of post-ganglionic motor transmission in the mammalian vas deferens by D-lysergic acid diethylamide.

1. Under certain conditions D-lysergic acid diethylamide (LSD), 10(-9)-10(-6) g/ml., exerted an immediate, prolonged and slowly reversible inhibitory effect upon the post-ganglionic motor transmission in desheathed guinea-pig vas deferens preparations.2. The most critical factor influencing this action of LSD appeared to be the train length. With short trains of less than 4 or 5 pulses the twitch inhibition produced by LSD was often total. With longer trains (5-20 pulses), the degree of inhibition declined with increase in train length. These results suggest the existence of two components in the motor response to post-ganglionic stimulation, distinguished by their susceptibility to LSD.3. The inhibition of the LSD-susceptible component was related to the dose of LSD in the range 10(-9)-10(-6) g/ml., reaching a maximum at 0.5-1 x 10(-6) g/ml. The response remnants elicited by trains of more than 5 pulses under these conditions could not be reduced further by a ten- to twenty-fold increase in LSD concentration to 10(-5) g/ml. and were in fact slightly potentiated.4. The inhibition of post-ganglionic motor transmission by LSD was not explicable on the basis of an alpha-adrenoceptor blockade because it was not associated with any reduction in motor responses to noradrenaline.5. The use of propranolol excluded mediation of the LSD-inhibition by beta-adrenoceptors.6. The LSD effect was not due to a non-specific smooth muscle depression because it was not associated with any reduction in motor responses to acetylcholine, ATP or bradykinin.7. The inhibitory effect of LSD on post-ganglionic transmission resembled that of noradrenaline in that it was antagonized by phentolamine; another alpha-adrenoceptor blocking agent, phenoxybenzamine, was less effective than phentolamine in this respect.8. The LSD-inhibition was obtained in preparations taken from reserpinized guinea-pigs.9. The inhibition of motor transmission in the vas deferens by LSD was confirmed in rats, Meriones shawii and rabbits.10. The inhibition of post-ganglionic transmission by LSD was unrelated to its ability to antagonize 5-hydroxytryptamine (5-HT), to which the longitudinal muscle of the guinea-pig vas deferens is insensitive. The more potent 5-HT antagonists, methysergide and BOL 148 were either virtually inactive or considerably weaker than LSD.

Acetylcholine↗

PubMed1987

The control of airway mucus secretion.

Airway mucus is essential for the effectiveness of cough and mucociliary transport. Even the resting airway produces some mucus but, under a great variety of threats to airway function, this production increases. A number of mechanisms may be responsible for augmenting secretion; these include reflexes, initiated by nervous receptors in the airways, and with their efferent limbs in the autonomic nerves to the airways. Cigarette smoke short circuits this reflex pathway; nicotine absorbed from the smoke stimulates ganglion cells directly and so drives secretion. Secretomotor nerves which control the output from submucosal glands include cholinergic, adrenergic and NANC fibres. A number of mediators of the sort released during inflammation and antigen challenge, including prostaglandins and leukotrienes, can also elicit secretion into the airway lumen. Other stimuli act at least partly on unknown mechanisms to release mucus from the surface epithelium into the airway lumen. For example inhalation of dust, which stimulates cough receptors and so acts partly by driving mucus secretion reflexly, also initiates secretion into the denervated airway. Similarly, during the inhalation of cool dry air, the airway lining secretes more mucus, probably by a non-nervous mechanism which responds to drying of the airway surface. More needs to be learned about such apparently direct mechanisms. Different control systems appear to stimulate the production of a variety of mucins from distinct cell types. We do not yet know the physiological and pathological importance of these differences.

Allergens↗

PubMed1985

A comparison of the stimulatory effects of metoclopramide and cinitapride in the guinea-pig isolated ileum.

The pharmacological effects of a new benzamide derivative cinitapride, have been compared to those of metoclopramide in guinea-pig isolated ileum and longitudinal smooth muscle-myenteric plexus preparations treated with propranolol (3 microM). Cinitapride (EC50 = 0.74 microM) was 6 times more potent than metoclopramide (EC50 = 4.69 microM) in enhancing the twitch response of co-axially stimulated preparations and 11 times more potent in eliciting contractions in non-stimulated tissues, their respective EC50 values being 0.58 microM and 6.52 microM. These contractile effects of cinitapride and metoclopramide amounted to approximately 25% of the maximum response of the tissues to acetylcholine (1 microM). Neither cinitapride nor metoclopramide, in concentrations up to 10 microM, significantly affected concentration-response curves to exogenous acetylcholine or 5-hydroxytryptamine but both drugs elicited a concentration-dependent potentiation of the ileum responses to a fixed concentration (10 microM) of the ganglion stimulant dimethylphenylpiperazinium (DMPP). Analysis of the twitch-enhancing and contractile effects of cinitapride using a variety of drugs suggested that a common, prejunctional locus of action upon the cell bodies or axons of postganglionic, parasympathetic neurones of the myenteric plexus is involved in both of these responses. In hexamethonium (100 microM) and methysergide (0.1 microM)-treated longitudinal smooth muscle preparations desensitization or blockade of 5-hydroxytryptamine receptors using high concentrations of the same agonist (30 microM) or quipazine (10 microM) or the putative antagonists cocaine (30 microM) or tubocurarine (10 microM) produced small inhibitions (congruent to 20%) of the contractile responses to metoclopramide and cinitapride but did not affect twitch responses to these drugs. It is concluded that cinitapride is a more potent stimulant of guinea-pig intestinal smooth muscle than metoclopramide in vitro although the mechanism of action of both drugs appears to be similar and involves a prejunctional enhancement of acetylcholine release from intramural cholinergic neurones. Attempts to implicate a prejunctional facilitatory 5-hydroxytryptamine receptor in the mediation of the stimulant effects of these drugs were not conclusive and additional studies are required to fully explore this possibility.

Acetylcholine↗