Showing papers on "Atropine published in 1980"

Serum levels of anticholinergic drugs in treatment of acute extrapyramidal side effects.

Abstract: • A simple, sensitive, and specific radioreceptor assay has been developed for the measurement of anticholinergic drugs in human serum. The assay is based on the competitive inhibition by free anticholinergic drugs in a 0.2-mL sample of serum with the specific binding of the potent muscarinic antagonists, tritiated quinuclidinyl benzilate, to solubilized brain muscarinic receptors. Anticholinergic activity could be detected regardless of drug structure and was quantified against atropine standards. Although the serum levels of anticholinergic drugs varied considerably in 35 patients receiving both neuroleptic and anticholinergic drugs, there was a highly significant inverse correlation between the presence of acute extrapyramidal side effects due to neuroleptics and the serum levels of anticholinergics.

Acetylcholine Inhibits the Release of Somatostatin from Rat Hypothalamus in Vitro

Abstract: Acetylcholine, at concentrations of 10(-10)--10(-7) M, inhibited the release of immunoreactive somatostatin (SRIF) from rat hypothalamic segments which had been maintained in short term culture for 24 h. Neostigmine (10(-6) M), an anticholinesterase, also inhibited the release of SRIF, whereas atropine (10(-6) M), a muscarinic anticholinergic, had no effect on basal SRIF release but blocked the inhibition caused by acetylcholine (10(-8) M). However, hexamethonium (10(-6) M), a nicotinic antagonist, did not abolish the inhibition induced by acetylcholine. Potassium depolarization (56 mM KCl) caused stimulation of SRIF release, which was dependent on the presence of calcium in the incubation medium. SRIF was measured by a RIA sensitive to 1 pg/tube. Authenticity of immunoreactive SRIF released was suggested by immunological parallelism and chromatographic criteria using gel and high pressure liquid systems. These results suggest that muscarinic cholinergic mechanisms may have a regulatory role modulating the secretion of SRIF and, consequently, GH through actions at a hypothalamic level.

The reflex control of heart rate and cardiac output in the rainbow trout: interactive influences of hypoxia, haemorrhage, and systemic vasomotor tone

Abstract: In cannulated trout there was no cholinergic vagal tone as revealed by atropine blockade during normal heart rates. Reductions in heart rate occasionally occurred under normoxia without apparent external stimuli (‘spontaneous’ bradycardia) and always occurred under environmental hypoxia (hypoxic bradycardia) due to the imposition of significant vagal tone. Direct measurements of cardiac output (Q) during these bradycardias showed that increases in cardiac stroke volume compensated for the falls in heart rate so that total Q remained unchanged or increased slightly. Sudden experimental reductions in arterial blood pressure via blockade of systemic vasomotor tone with yohimbine or via haemorrhage had no effect on heart rate during normal rates, but caused cardioacceleration during both types of bradycardia. These increases in heart rate never exceeded the point of zero vagal tone (normal heart rate) and were largely or wholly due to reductions in endogenous vagal tone. These cardioaccelerations were temporary; spontaneous bradycardia could re-occur at any time, while hypoxic bradycardia always re-occurred if the hypoxic stimulus were maintained. The results are interpreted in terms of a central interaction between the baroreceptor and chemoreceptor reflexes.

Modulatory effect of brain acetylcholine on reflex-induced bradycardia and tachycardia in conscious rats.

Abstract: The effects of intracerebroventricular (i.c.v.) injection of physostigmine and hemicholinium-3 (HC-3) on reflex bradycardia and tachycardia have been studied in unanesthetized rats. The reflex increases and decreases in heart rate were elicited by i.v. injection of norepinephrine and sodium nitroprusside, respectively. Physostigmine (5-10 micrograms) increased basal mean arterial pressure (MAP), reduced basal heart rate (HR), enhanced the reflex bradycardia and reduced reflex tachycardia. Physostigmine did not modify either the pressor effect of norepinephrine, the depressor effect of sodium nitroprusside or the responsiveness of peripheral muscarinic receptors. Pretreatment (i.c.v.) with atropine (0.3 micrograms) completely abolished the effect of physostigmine on MAP, HR, reflex bradycardia and reflex tachycardia. Pretreatment (i.c.v.) with mecamylamine (50 micrograms) did not modify the effect of the cholinesterase inhibitor on MAP, HR and reflex tachycardia, but inverted its effect on reflex bradycardia. Injection of HC-3 (20 micrograms i.c.v.) did not modify MAP, but reduced HR and inhibited both reflex bradycardia and reflex tachycardia. The HC-3 bradycardic effect started within minutes and lasted for about 1 hr, while the depressor effect on the reflexes began only after 15 min and continued for several hours. In addition, i.c.v. pretreatment with HC-3 completely abolished all the effects of physostigmine on MAP, HR, reflex bradycardia and reflex tachycardia. These results suggest that brain acetylcholine has a modulatory effect on baroreceptor reflexes. This modulation operates through muscarinic receptors in reflex tachycardia and through both muscarinic and nicotinic receptors in reflex bradycardia.

Anticholinergic effects of disopyramide and quinidine on guinea pig myocardium. Mediation by direct muscarinic receptor blockade.

Abstract: We studied the interaction of disopyramide, quinidine, and procainamide with cardiac muscarinic receptors. In electrophysiological experiments, the effects of disopyramide, quinidine, procainamide, and atropine were determined on spontaneously depolarizing guinea pig right atria (GPRA) both in the presence and absence of pharmacologically induced (physostigmine) cholinergic stimulation. All four agents demonstrated a concentration-dependent antagonism of the negative chronotropic effects of physostigmine. The order of anticholinergic potency was atropine greater than disopyramide greater than quinidine greater than procainamide. The ability of disopyramide to antagonize the physostigmine induced slowing was stereoselective, (+)disopyramide greater than (-)disopyramide. In contrast, the ability of quinidine to antagonize the negative chronotropic effects of physostigmine was non-stereoselective, quinidine = quinine. In parallel experiments, we studied the ability of disopyramide, quinidine, procainamide, and atropine to compete with the radiolabeled muscarinic receptor antagonist [3H] quinuclidinyl benzilate ([3H]QNB) for binding to muscarinic receptors in crude homogenates of GPRA and membrane vesicles from canine ventricular myocardium. All four agents inhibited [3H]QNB binding to muscarinic receptors. The order of anticholinergic potency determined by the receptor binding studies was identical to that determined by the physiological studies. The interaction of disopyramide with muscarinic receptors was stereoselective, (+)disopyramide > (-)disopyramide. Quinidine was only slightly more potent than quinine in inhibiting [3H]QNB binding to muscarinic receptors. Interaction of antiarrhythmic drugs with muscarinic receptors satisfied criteria for a competitive interaction. The data from this study localize the anticholinergic effects of disopyramide and quinidine to the muscarinic receptor.

Mechanisms of tachycardia on standing: studies in normal individuals and in chronic Chagas' heart patients.

Abstract: The reflex tachycardia induced by change from the supine position to a 70 degree head-up tilt was studied in conscious normal individuals and in patients with chronic Chagas' heart disease, known to constitute a model of parasympathetic denervation of the sinus node, in the absence of cardiac failure. Chagas' patients showed markedly decreased heart rate responses during the initial 10 s following tilt to upright posture. A similar response was obtained in normals after parasympathetic blockade with atropine. beta-Adrenergic blockade failed to produce a significant effect on the initial heart rate response of normals, but heart rate increment, at 1 and 5 min of tilt, was significantly reduced in normals and abolished in patients. These results indicate a biphasic mode of tachycardia elicited by the upright posture; initially it depends on parasympathetic withdrawal, sympathetic stimulation becoming the predominant mechanism when stabilisation is attained in the orthostatic position.

Bronchodilatation: noncholinergic, nonadrenergic mediation demonstrated in vivo in the cat

Abstract: The composite vagus nerve was stimulated during intravenous infusion of 5-hydroxytryptamine in cats subjected to pharmacologic autonomic blockade with atropine, propranolol, and phentolamine. Bronchial caliber, as assessed by changes in pulmonary resistance, demonstrated a marked dilatation, and dilatation could still be demonstrated after preliminary treatment with reserpine. By stimulating the component branches of the vagus nerve, it was determined that the parasympathetic branch is responsible for this phenomenon.

Adrenergic and cholinergic nerves mediate fluid secretion from tracheal glands of ferrets

Abstract: Our aim was to determine whether adrenergic as well as cholinergic nerves mediate secretion of fluids from tracheal submucosal glands and, if so, via which receptors. To do this, we studied the secretory responses of tracheal segments to electrical and pharmacologic stimulation in vitro in the presence and absence of a specific nerve blocker and autonomic antagonists. Stimulation caused small elevations, or "hillocks," the size of which we estimated by measuring their diameters. We found that electrical stimulation, acetylcholine, and phenylephrine each caused secretion but that terbutaline did not. Tetrodotoxin prevented the secretory response to electrical stimulation but did not prevent the responses to acetylcholine or phenylephrine. Neither atropine nor phentolamine alone prevented the response to electrical stimulation, but both drugs together did, and propranolol did not inhibit the adrenergic component of the response to electrical stimulation. Atropine blocked the response to acetylcholine, and phentolamine blocked the response to phenylephrine. We conclude that adrenergic and cholinergic nerves mediate secretion from the tracheal glands of ferrets via alpha-adrenergic and muscarinic receptors, respectively.

Some direct and reflex cardiovascular actions of prostacyclin (PGI2) and prostaglandin E2 in anaesthetized dogs.

Abstract: 1 The aim of the study was to determine the mechanism of the hypotension and bradycardia produced by prostacyclin (PGI2). 2 Haemodynamic studies were carried out in nineteen open-chest beagle dogs anaesthetized with chloralose. PGI2 was infused intravenously or into the left atrium. 3 Infusions of PGI2 either intravenously or into the left atrium equally reduced arterial pressure and total peripheral resistance but bradycardia was greater after infusion into the left atrium. 4 Comparison of effects of PGI2 with those of prostaglandin E2 (PGE2) showed that although left atrial infusions both reduced aortic pressure and total peripheral resistance, PGE2 always increased heart rate, cardiac output and maximum acceleration. 5 Similar effects were observed with sodium nitroprusside except that it always caused tachycardia and reduced stroke volume. 6 Atropine (0.05 or 1 mg/kg i.v.) reduced or reversed the bradycardia induced by PGI2 but its hypotensive effects were reduced only after 1 mg/kg atropine. After vagotomy changes in cardiac output, stroke volume and maximum acceleration were increased, the hypotensive effects of PGI2 were reduced and the bradycardia was reversed; effects induced by PGE2 were not significantly altered. 7 The hypotension induced by prostacyclin is due to two components, a direct relaxation of vascular smooth muscle and a reflex, non-cholinergic vasodilatation. The bradycardia is reflex in nature and is partially mediated by the vagus pathway.

Plasma atropine concentrations determined by radioimmunoassay after single-dose i.v. and i.m. administration

Abstract: SUMMARY The plasma concentrations of atropine following i.v. or i.m. administration to surgical patients were determined by radioimmunoassay. When atropine sulphate 1 mg was given i.v. there was a rapid initial removal of the drug from the circulation in the first 10 min; thereafter the plasma concentration decreased more slowly. Atropine i.m. was rapidly absorbed with peak concentrations occurring at 30 min following injection. The plasma atropine concentration then decreased slowly, probably because of uptake of atropine by muscarinic cholinergic receptors. The chronotropic effect of atropine appeared to correspond to the concentration in plasma following i.m. administration. We conclude that i.m. atropine, as a premedication, should be given not later than 30 min before induction of anaesthesia.

Evaluation of glycopyrrolate and atropine as adjuncts to reversal of non-depolarizing neuromuscular blocking agents in a “true-to-life” situation

Abstract: Glycopyrrolate, a quaternary ammonium anticholinergic compound, and atropine were evaluated in combination with neostigmine for antagonism of non-depolarizing neuromuscular block. A total of 641 patients were investigated in a "true-to-life" situation. The patients receiving glycopyrrolate with neostigmine had smaller changes in heart rate than those who received atropine. This was particularly apparent in patients with cardiovascular disease.

Comparison of the effects of atropine and glycopyrrolate on various end-organs.

Abstract: Atropine and glycopyrrolate (glycopyrronium bromide), a quaternary ammonium drug, were evaluated in volunteers following intramuscular administration with respect to effects on various end-organs with cholinergic innervation. Glycopyrrolate appears to be five to six times more potent than atropine in its antisialogogue effect and also exhibits a selective, though prolonged, effect on salivary secretion and sweat gland activity. It has minimal cardiovascular, ocular and central nervous system effects.

Changes in Vagal Activity and Response to Muscarinic Receptor Agonists With Age

Abstract: The response to vagal nerve and muscarinic receptor stimulation was evaluated in young (90 day), adult (365 day) and old (730 day) male F-344 rats anesthetized with urethane. Bilateral vagotomy produced a significant increase in heart rate in the young and adult animals (p < 0.05), while no change in heart rate occurred in the old animals. Stimulation of the right vagus nerve produced a frequency dependent decrease in response to right vagus nerve stimulation with age (p < 0.05; analysis of variance), i.e., old animals had a smaller decrease in heart rate over the same frequency range of nerve stimulation than either the young or adult animals. The effect of age on the response of the muscarinic receptor was examined using cumulative doses of methacholine administered by bolus injection. Methacholine produced a dose dependent decrease in heart rate and blood pressure. The heart rate response to methacholine was diminished in the older animals (p < 0.05; analysis of variance). Similar results were obtained after atropine although the doses of methacholine employed were much greater. In contrast, although methacholine decreased blood pressure in all animals at each age there was no change in the hypotensive response to methacholine with age. These data indicate that there is a diminution in vagal control of heart rate with age as well as the response of the vagus nerve to stimulation. Furthermore, the response of the muscarinic receptor in the heart declines with age while that in the peripheral vasculature does not.

Comparative study of the smooth muscle layers of the rabbit duodenum.

Abstract: 1 Intracellular electrodes were used to compare the electrical activity of smooth muscle cells from the longitudinal and circular layers of the rabbit duodenum and their responses to stimulation of the intramural nerves 2 The longitudinal muscle cells had an average membrane potential of 52 mV when measured between slow waves Spontaneous action potentials were superimposed on every slow wave 3 The circular muscle cells had a higher membrane potential of 64 mV although the amplitude of the slow waves was similar to that of the longitudinal muscle cells Spontaneous action potentials were rarely observed in the circular muscle cells 4 Lowering the temperature from 36 to 30 degrees C caused a reduction in the membrane potential of the longitudinal muscle cells but not in the circular muscle cells However, the amplitude of the slow waves of the two layers was reduced to a similar extent 5 Electrical stimulation produced advances of the slow wave cycles if the stimuli were applied between slow waves The responses of the cells from the two layers were identical 6 Under normal conditions, electrotonic coupling was observed only in cells of the muscle layer whose long axis was aligned along the direction of the applied current 7 In the longitudinal muscle, cholinergic responses blocked by atropine were observed Inhibitory potentials were the predominant response in the circular muscle 8 Excitatory responses were recorded in 9% of the circular muscle cells "Off' excitation following termination of a train of repetitive stimulation pulses was also observed 9 The differences in membrane potentials, spontaneous spiking activities, neural responses, and the failure to demonstrate good electrotonic coupling between the muscle layers suggest that there was poor electrotonic interaction between the muscle layers The amplitude of the slow waves of the two layers was nevertheless similar Thus the validity of the hypothesis that slow waves were transmitted passively from the longitudinal layer into the circular layer through electrotonic coupling must be questioned

Coronary vasoconstriction by locally administered acetylcholine, carbachol and bethanechol in isolated, donor-perfused, rat hearts.

Abstract: 1 Experiments were carried out on rat isolated heart preparations in which the coronary vasculature was perfused through the aorta at a constant flow rate with arterial blood from donor animals. Single doses of drugs were injected into the aortic cannula. 2 Small doses of acetylcholine, carbachol or bethanechol decreased perfusion pressure (PP) without markedly affecting left ventricular pressure (LVP) and heart rate (HR); larger doses of these drugs increased PP (vasoconstriction), and decreased LVP and HR in a dose-dependent manner. 3 Acetylcholine, carbachol and bethanechol had almost no effects when perfused through the aorta in such a way as to exclude the coronary vessels. 4 Coronary vasoconstriction in response to acetylcholine, carbachol and bethanechol was not significantly affected by reserpine pretreatment, phentolamine or hexamethonium, but was antagonized by small doses of atropine. 5 From these results it is concluded that in the coronary vasculature of the rat, the receptors involved in the vasoconstrictor actions of acetylcholine carbachol and bethanechol are muscarinic.

Structural and functional study of control of canine tracheal smooth muscle.

Abstract: The structural bases for myogenic and neurogenic control of canine tracheal smooth muscle were studied. At optimum lengths, strips of muscle showed insignificant neurogenic or myogenic tone. Atropine and/or tetrodotoxin blocked the contractile responses elicited on electrical field stimulation of intrinsic nerves. After raising the tone with tetraethylammonium ion and in the presence of atropine, field stimulation of nerves caused a relaxation, a major component of which was blocked by propranolol and/or tetrodotoxin, suggesting an effect mediated through interaction of mediator released from sympathetic nerves with beta-adrenergic receptors. Electron microscopic studies revealed gap junctions between extensions of smooth-muscle cells and a sparse innervation. The axonal varicosities, corresponding to cholinergic (predominantly) and adrenergic (occasionally) nerves, were seen predominantly in the clefts between cell bundles. The physiological responses were compared with the morphological features. Although this muscle exhibits multiunit behavior in vitro, implying that nerves initiate the coordinate activity, its ultrastructural features suggest a potential for single-unit behavior.

Effects of pirenzepine and atropine on gastric secretory and plasma hormonal responses to sham-feeding in patients with duodenal ulcer.

Abstract: The effects of atropine and pirenzepine on sham-feeding stimulated gastric secretion and serum gastrin and pancreatic polypeptide levels have been studied in 12 patients with duodenal ulcer. Both atropine and pirenzepine caused a dose-dependent decrease in acid and pepsin secretion induced by sham-feeding. Serum gastrin response to sham-feeding was negative and it was enhanced by atropine but suppressed by pirenzepine. Plasma pancreatic polypeptide level, which was markedly increased by sham-feeding, was abolished both by atropine and pirenzepine. This study shows that pirenzepine is a more selective inhibitor of gastric secretory and serum hormonal responses to sham-feeding than atropine and that it may be a useful tool for studying the cholinergic innervation of the oxyntic glands and the G-cells in man.

Pre- and postjunctional effects of prostaglandin E2, prostaglandin synthetase inhibitors and atropine on cholinergic neurotransmission in guinea pig ileum and bovine iris.

Abstract: The effects of prostaglandin E2, arachidonic acid, prostaglandin synthetase inhibitors and atropine on cholinergic neuromuscular transmission were examined in isolated guinea pig ileum longitudinal muscle and bovine iris sphincter muscle. Prostaglandin E2 and arachidonic acid markedly enhanced contraction responses induced by nerve stimulation. In addition, prostaglandin E2, enhanced contraction responses to acetylcholine and direct muscle stimulation, approximately to the same extent as those to nerve stimulation. Prostaglandin synthetase inhibitors (indomethacin, meclofenamic acid and eicosatetraynoic acid) very effectively reduced contraction responses to nerve stimulation or acetylcholine, and they annulled the stimulant effect of arachidonic acid. Basal and nerve-induced efflux of acetylcholine from the eserinized tissues, as measured by mass fragmentography, was unaltered by prostaglandin E2, but diminished slowly during indomethacin. Subsequent prostaglandin administration caused a slight increase of nerve-induced release of acetylcholine. Atropine markedly increased overflow of acetylcholine form stimulated preparations of both types. This indicates that muscarinic receptors, causing diminished acetylcholine release in eserinized tissue, may be present also at postganglionic terminals. During atropine, an effect of prostaglandin E2 on acetylcholine release could still not be seen. Thus, using physicochemical determination of acetylcholine, we could not verify earlier reports, employing bioassay, claiming enhanced release of transmitter during prostaglandin E2 treatment. However, it seems likely that prostaglandin E2 takes part in the regulation of contractility and tone of the smooth muscle cells.