[On the antidiuretic reaction provoked by parasympathomimetics in conscious and alcohol-anesthetized rats].
Explore the source record for details and available documents.
Acetylcholine↗
SEARCH · Search PubMed
Results for “PARASYMPATHOMIMETICS”
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
[The use of direct and indirect parasympathomimetics in poisonings with tricyclic antidepressive agents].
The use of cholinesterase inhibitors in poisonings with potentially lethal doses of tricyclic antidepressive drugs seems to be indicated on account of clinical experiences and own experimental investigations on animals. An uncritical use of these substances which have considerable side-effects must be warned of. A mixed intoxication with several drugs effecting on the central nervous system is only a relative indication for the use of indirect parasympathicomimetics of the cholinesterase type. They should be used only then, when the picture of poisoning is unequivocally determined by the thymoleptics. When cholinesterase inhibitors are used the physostigmine salicylate should be preferred, since at present it is sufficiently accessible to the central nervous system and with the slightest peripheral effects as the only representative of this group of substances, above all with regard to the gastrointestinal motility. Later investigations shall show, whether also other groups of substances which develop an antagonistic effect to the tricyclic antidepressive drugs may be of use in the treatment of the acute poisoning.
Amitriptyline↗
On a cholinergic motor innervation of the rat urethra.
Choline acetyltransferase activity was demonstrated in the proximal part of the male rat urethra, indicating a cholinergic innervation of this tissue. The cholinergic nerve fibres emanated evidently from the pelvic nerves, since bilateral removal of the pelvic ganglion caused a major fall in the activity of this enzyme. The muscle activity of the circular layer of the proximal urethra was recorded in vitro. The basal activity of this segment was low. The parasympathomimetics acetylcholine and methacholine, evoked rapid and marked contractile responses; the maximal responses to these drugs were 36 and 44%, respectively, of that to potassium. The corresponding figures for phenylephrine and noradrenaline were found to be 79 and 88%, respectively. The responses evoked by the parasympathomimetics were unaffected by the ganglion blocker hexamethonium, the alpha-adrenoceptor blocker dihydroergotamine and the beta-adrenoceptor blocker propranolol. Atropine, however, abolished the responses completely. Following degeneration of adrenergic or cholinergic nerves of the urethra the parasympathomimetics still evoked contractions. Taken together these findings indicate that the parasympathomimetics exert their contractile effect through a direct action on muscarinic receptors. Parasympathectomy but not sympathectomy (caused by 6-hydroxydopamine treatment) gave rise to a supersensitivity to methacholine, as judged by a leftward shift of the dose-response curve for this drug, the ED50-value being ten times less than that of the controls. The observations seem to suggest that the proximal urethra normally is under the influence of cholinergic activity beside that of adrenergic activity previously demonstrated.
Animals↗
Clinical implications of differences in pharmacodynamic action of polar and nonpolar cardiac glycosides.
The principal effects of cardiac glycosides probably can be classified as parasympathomimetic or sympathomimetic. Data from animals and from man suggest that polar cardiac glycosides, such as ouabain and digoxin, possess greater parasympathomimetic (vagal) cardiac effect for a given amount of sympathomimetic (positive inotropic) cardiac effect than do less polar cardiac glycosides, such as digitoxin. Polar glycosides therefore offer some advantage in uncomplicated paroxysmal atrial tachycardia and in uncomplicated atrial flutter and atrial fibrillation when the principal desired effect is reduction in the number of atrial impulses reaching the ventricles or conversion to normal sinus rhythm. Non-polar glycosides offer an advantage when positive inotropicity is desired but when there is some degree of atrioventricular block or when inappropriate sinus bradycardia or anorexia, nausea, or vomiting are present. Ecotopic impulse formation when due to cardiac glycosides is a toxic manifestation of excessive sympathomimetic effect, but is aggravated by vagal-induced sinus bradycardia, so that both parasympathomimetic and sympathomimetic capability of cardiac glycosides must be considered when dealing with myocardial electrical instability.
Animals↗
Investigation of central cholinergic mechanisms in the conscious mouse.
1. An investigation of central cholinoceptors in the mouse has been made by injecting cholinomimetic drugs into the cerebral ventricles and seeing how their effects were modified by prior administration of atropine-like substances and other drugs.2. Carbachol or oxotremorine injected in small doses intracerebroventricularly into conscious mice caused hypothermia, gross tremor and a variety of parasympathomimetic effects including lachrymation and salivation. Acetylcholine injected in this way was active only in much larger doses.3. Methacholine and pilocarpine also caused a variety of parasympathomimetic effects after intracerebroventricular injection but virtually no hypothermia or tremor.4. Nicotine injected intracerebroventricularly caused mild hypothermia, fine tremor but no parasympathomimetic effects.5. Atropine-like drugs, tricyclic antidepressants and amphetamine antagonized the hypothermia induced by intracerebroventricular carbachol or oxotremorine.6. The sites of action of the atropine-like drugs are in the brain; those of the tricyclic antidepressants and amphetamine are in the periphery probably on heat generating beta-adrenoceptor mechanisms.7. It is concluded that the atropine sensitive cholinoceptors in the brain vary in their sensitivities to cholinomimetic drugs, other than acetylcholine, and may exist in isoreceptor forms.8. Peripheral atropine sensitive cholinoceptors may also exist in isoreceptor forms.
Acetylcholine↗
Regulation of salivary kallikrein secretion in submandibular gland.
Unstimulated pairs of rat submandibular glands were compared with regard to their wet weight, total protein content and kallikrein antigenic activity. Paired glands from the same animal were found to be comparable, whereas differences from one animal to another were considerable. One of two paired glands was extirpated and used as control, and the other was subsequently subjected to stimulation. Salivary secretion was induced parasympathomimetically (intraperitoneal injections of pilocarpine; perfusion with acetylcholine and electrical stimulation of the ductal nerve plexus near the gland hilus) or sympathomimetically (cervical sympathetic nerve stimulation with or without administration of alpha- or beta-adrenergic blocker; perfusion with epinephrine, norepinephrine or isoproterenol). The effect was studied by measuring the change in total gland kallikrein content and by quantitation of kallikrein in saliva. A small secretion of kallikrein was always observed. However, alpha-adrenergic stimulation was 40 and 1 500 fold more effective in releasing kallikrein than beta-adrenergic and parasympathomimetic stimulation, respectively. Also, significantly more kallikrein was released by beta-adrenergic than parasympathomimetic stimulation. Immunohistochemistry confirmed the observed depletion of kallikrein following alpha-adrenergic stimulation. No alteration in kallikrein localization was observed in stimulated glands.
Acetylcholine↗
Bacterial agglutinins in rat salivary glands: effect of glandular stimulation and calcium dependency.
The secretory pattern of salivary, bacterial agglutinins was studied in the rat. The three major salivary glands were cannulated bilaterally and their secretions collected separately after parasympathomimetic and sympathetic stimulation. The bacterial aggregating activity of the secretions was tested against four strains of bacteria indigenous to the rat. Agglutinin activity was demonstrated in both parasympathomimetic and sympathetic secretions. The parotid glands tended to show the highest total output of agglutinins, with the highest titers found in parotid saliva on sympathetic stimulation. In submandibular and, particularly, parotid saliva, titers tended to increase when stimulation with pilocarpine was followed by sympathetic stimulation. In contrast, titer in sublingual saliva tended to decrease on sympathetic stimulation. When expressed as titer output per minute, sympathetic parotid secretion showed the highest agglutinin activity. Agglutinin activity appeared unrelated to total protein or to duct-derived amidolytic activity. Titers of parotid or submandibular saliva were increased 5- to 10-fold by the presence of 3.3 mM CaCl2 in the reaction mixture. By contrast, the agglutinating activity of sublingual saliva on parasympathomimetic stimulation was unaffected by extraneous CaCl2. Measurements of Ca concentration in similarly obtained rat salivary secretions did not show patterns of Ca concentration that could be related to the varying sensitivity of the agglutinating activity to Ca.
Agglutinins↗
Evidence against a role for guanosine 3',5'-cyclic monophosphate in rat submandibular salivary gland potassium release.
The role of guanosine 3',5'-cyclic monophosphate (cGMP) in the net K+ efflux following parasympathomimetic and sympathomimetic stimulation in dispersed rat submandibular cells was evaluated. In unstimulated cells, approx. 70 per cent of the total cGMP content was present in the incubation medium; the addition of 1-methyl-3-isobutylxanthine (MIX), a phosphodiesterase inhibitor, to the medium elevated both intracellular and extracellular levels of cGMP. Cholinergic receptor stimulation resulted in a rapid increase of the cGMP content in the cells and in the medium. Extracellular Ca2+ was necessary for an increased cGMP response and MIX potentiated the cGMP response. Adrenergic-receptor activation produced a slight increase in cGMP after 5 min of stimulation but only when MIX was present in the medium. cGMP analogues (8-Br-cGMP and Bt2cGMP) had no effect on the rate of maximal net K+ efflux, on submaximal net K+ efflux, or on K+ re-uptake following parasympathomimetic or sympathomimetic stimulation. The dose-response relationship for a cholinergic agonist, carbamylcholine, or an adrenergic agonist, norepinephrine, was unaffected by the presence of either 8-Br-cGMP or Bt2cGMP in the medium. MIX, at a concentration sufficient to increase intracellular and extracellular cGMP levels, had no effect on net K+ efflux. These data do not support a role for cGMP in modulating rat submandibular potassium release.
1-Methyl-3-isobutylxanthine↗
Miotics: side effects and ways to avoid them.
Pilocarpine, a parasympathomimetic drug used in the treatment of glaucoma, produces a variety of ocular and systemic adverse reactions. Ocular side effects include miosis, accommodative spasm, frontal headaches, twitching lids, conjunctival injection, cataractous changes, allergic reactions, iris cysts, retinal detachment, increased permeability of the blood-aqueous barrier, anterior chamber narrowing, and the potential for inducing an acute angle-closure attack. Systemic side effects include nausea, vomiting, tenesmus, abdominal spasm, salivation, lacrimation, sweating, pulmonary edema, and bronchial spasm. The systemic side effects can best be minimized initially through proper use of the medication and nasolacrimal occlusion. The Ocusert, a long-acting pilocarpine-incorporated ocular insert, is a recent advance in delivery technique that offers an adequate hypotensive action with fewer side effects. Pilopex is a promising new experimental pilocarpine polymer salt presently being studied in Israel. Photomydriasis, a process involving the use of a laser to enlarge miotic pupils also offers help for these patients. N-demethylated carbachol is a new parasympathomimetic drug currently under study for glaucoma therapy. Initial results show that it may have considerable ocular hypotensive action with fewer adverse effects.
Carbachol↗
[Stopping smoking and constipation].
INTRODUCTION: Among the symptoms that may occur with smoking withdrawal, constipation is relatively frequent, but little studied. CASE: Three women reported that constipation developed when they stopped smoking and improved during transient relapses. DISCUSSION: This constipation sometimes produces serious functional disorders and can induce relapse. It occurs especially among women and those predisposed to it. Nicotine, by acting on the parasympathomimetic system, increases intestinal peristalsis, and a cigarette can appear to be effective self-medication. Magnesium salts are the first-line treatment for this problem. If they fail, neostigmine, an anticholinesterase with parasympathomimetic activity, appears remarkably effective in correcting this disorder.
Cholinesterase Inhibitors↗
Systemic and local tolerability of ophthalmic drug formulations. An update.
All eye drops raise problems of local tolerance, but with variable frequencies. They can induce pain on instillation, allergic reactions, delayed healing, punctate keratitis, disturbances of lacrimal secretion, disturbances of accommodation (especially the parasympathomimetics) and local pigmentation after prolonged use. Corticosteroids are associated with 2 major risks: chronic glaucoma and cataract, initially reversible if treatment is stopped. There is still a major risk of corneal herpes with corticosteroids. It is important to be aware of these local problems as they are responsible for poor patient compliance. The systemic effects essentially concern the agonists and antagonists of the autonomic nervous system. beta-Blocker eye drops can cause bronchospasm, heart failure, syncope and psychiatric disorders, especially at high doses and with nonselective beta-blockers. These consequences are usually related to failure to comply with the prescribing precautions. alpha-Adrenergic agonists, which exert dose-dependent effects, can induce hypertensive crises or angina attacks. Apart from patients at risk (children under the age of 30 months and the elderly), parasympathomimetics cause few systemic adverse effects; anticholinesterases, which have curare-like properties, are contraindicated for 6 weeks before general anesthesia. In the very young and the very old, atropinic eye drops carry a risk of cardiovascular collapse and neuropsychiatric disturbances. Problems may also occur with other classes of drugs such as anti-infectives, antispectics, anti-inflammatories and contact lens products. Nevertheless, it is clear that this form of treatment is generally very well tolerated in relation to the volume of eye drops prescribed by ophthalmologists each day.
Adrenal Cortex Hormones↗
[Parasympathetic control of secretion of pancreatic juice in the rabbit (author's transl)].
The secretion of pancreatic juice in response to stimulation of the vagus nerves in the neck, and to injection of parasympathomimetic drugs, was studied in anesthetized rabbits. Vagal stimulation caused a marked increase of protein content in pancreatic juice, and also a small increase in flow of juice, highly variable from one amimal to another, preceded by a short period of inhibition. Atropine supressed vagal effect on protein concentration, but failed to abolish the flow response. Injection of parasympathomimetic drugs closely imitated the results of vagal stimulation, with the difference that secretory action was fully abolished by atropine. The possibility that effects the parasympathetic stimulation on the flow of juice were secondary to vasodilatation, was discussed. The obtained data were compared with those described for other mammalian species, and the conclusion was reached that rabbit behaves like carnivora rather than herbivora.
Animals↗
The action of physalaemin on electrolyte excretion by the mandibular and sublingual salivary glands of the rat.
The effect of physalaemin, an undecapeptide belonging to a family known collectively as the tachykinins, on water and electrolyte excretion of the mandibular and sublingual salivary glands of the rat has been investigated and compared to that of acetylcholine. Drugs were administered intravenously or by close-arterial infusion. Physalaemin is a powerful stimulant of fluid secretion by both glands although less potent than acetylcholine. The Na and K excretion patterns in physalaemin-evoked saliva resembled, but were by no means identical to those evoked by acetylcholine and other parasympathomimetic drugs: saliva evoked by physalaemin was considerably poorer in Na and K at all secretory rates. The HCO3 excretion curves, on the other hand, seemed to be identical to those evoked by parasympathomimetic drugs. From an analysis of the Na and K excretion patterns, it can be concluded, both for the mandibular and the sublingual glands, that physalaemin stimulated Na reabsorption and K secretion across the gland duct epitheluim, whereas acetylcholine has the opposite effect. These findings agree nicely with what has previously been demonstrated in vitro in the isolated perfused main excretory duct of the rat mandibular gland.
Acetylcholine↗
Anticholinesterase activity of the unsymmetric bisquaternary 6-aminoquinoline salt NSC-176319.
The anticholinesterase activity of the unsymmetric bisquaternary 6-aminoquinoline salt NSC-176319 (QB) was studied in vitro. QB proved to be a noncompetitive inhibitor of both acetylcholinesterase (or true cholinesterase) and butyrylcholinesterase (or pseudocholinesterase) having a KI = 0.5 X 10(-6) M for acetylcholinesterase and 1.5 X 10(-6) M for butyrylcholinesterase. Further, QB inhibited esterase activity of murine plasma in a noncompetitive manner (KI = 4.2 X 10(-6) M). The inhibition was instantaneous in onset and did not diminish with prolonged incubation of the drug and enzyme. All mice treated intravenously with 2 mg QB/kg died within 5 min. Prior to death, mice developed severe parasympathomimetic effects and convulsions. Although the parasympathomimetic effects were diminished by atropine sulfate pretreatment, death could only be prevented by barbiturate anesthesia.
Animals↗
Results of an epidemiological study on drug-treated intraocular hypertension in Belgium.
Some epidemiological aspects of drug-treated intraocular hypertension in Belgium were established in 1992 from questionnaires filled in by 1513 patients who attended a sample of 209 pharmacies open to the public. The mean age of the patients was 67 years (range: 3-95). After standardization for age, the prevalence of diabetes mellitus among patients was found to be 1.7 times higher than in the general population. Family history of glaucoma and/or blindness was reported by 28% of the patients. Beta-blocker eye drops were used by 96% of the sample. An ophthalmologist was consulted more than four times a year by 24% of the patients who had been drug-treated for less than one year; the proportion, however, decreases to 11% for those treated for at least five years. The annual consumed dose of eye drops containing parasympathomimetics, beta-blockers, and epinephrine or dipivefrine was 12.4, 13.6, and 12.3 bottles, respectively, and that of ointments containing parasympathomimetics was 9.9 tubes. From these results and using sales figures, the prevalence of drug-treated intraocular hypertension was found to be 77 per 10,000 inhabitants (95% CI: 31-123).
Adolescent↗
Experimental model for paroxysmal atrial fibrillation arising at the pulmonary vein-atrial junctions.
BACKGROUND: The mechanism(s) by which pulmonary veins (PVs) become ectopically active and subsequently initiate and sustain atrial fibrillation (AF) remains poorly understood. OBJECTIVES: The purpose of this study was to produce an acute canine model of paroxysmal AF arising from the PVs. METHODS: In 11 dogs, a thoracotomy was performed and a 26-gauge needle with a polyethylene tube attached was inserted into a fat pad containing autonomic ganglia at the base of the PV. The 11 dogs were divided into two groups: acetylcholine (ACh) 1-10 mM (group I, n = 5) or carbachol (CARB) 1-10 mM (group II, n = 6) injected (0.5 mL) into the fat pad. RESULTS: Within 2 to 5 minutes after injection of parasympathomimetics into the fat pad, a sequence of heart rate slowing, spontaneous premature depolarizations, and spontaneous AF was observed in four of 11 dogs. In seven dogs, single premature extrastimuli easily induced AF. AF was sustained for an average of 10 minutes (ACh) and 38 minutes (CARB), with the shortest AF cycle length seen at the PV-atrial junction adjacent to the fat pad (AF cycle length 75 +/- 41 ms for ACh and 37 +/- 12 ms for CARB). CONCLUSION: Acute autonomic remodeling produced by injection of parasympathomimetics into the fat pad resulted in spontaneous or easily induced sustained AF with short AF cycle length; the most rapid firing rate was observed in the PV and atria adjacent to the injected fat pad. These findings resemble paroxysmal AF in patients, suggesting that hyperactive autonomic ganglia may be a critical element in patients exhibiting focal AF arising from the PV.
Acetylcholine↗
Evaluation of the role of neurolinins and urecholine hypersensitivity in an animal model of infravesical outflow obstruction.
OBJECTIVES: To determine whether detrusor muscle strips from a male rat with infravesical outflow obstruction model demonstrate supersensitivity to parasympathomimetic and neurokinin NK-1 and NK-2 selective agonists. METHODS: Bladder instability developed after 6 weeks of partial urethral obstruction. The micturition frequency and voided volume were determined in unanesthetized animals. Detrusor hypertrophy was confirmed by evaluation of bladder weight. In vitro organ bath was used to compare the affinity and maximal activity of bethanechol and neurokinin NK-1 and NK-2 selective agonists on strips from the detrusor muscle of sham and obstructed rats. Bethanechol, N-Ac[Arg6, Sar9, Met(O2)]-SP(6-11), and [beta-Ala8]-NKA(4-10) were used to characterize cholinergic muscarinic, neurokinin NK-1 and NK-2 receptors. Results. No significant differences in affinities and maximal responses were found using 10-mg detrusor muscle strips with each of the three agonists. CONCLUSIONS: Bladder instability produced by outlet obstruction does not involve changes in the affinity or maximal activity of cholinergic muscarinic, neurokinin NK-1 and NK-2 receptors. Furthermore, detrusor supersensitivity to neurokinins or bethanechol was not seen. This suggests that bladder instability is not due to an increased affinity or maximal response to neurokinins or parasympathomimetics.
Animals↗
The effect of oxotremorine on in-vitro secretion of parathyroid hormone.
The effect of the muscarine-like acting parasympathomimetic drug oxotremorine and its antagonist atropine on PTH release was tested using single cell suspensions obtained from a) primary parathyroid adenomas, and b) secondary hyperplastic parathyroid tissue from patients undergoing chronic hemodialysis. For both cell-types we found a dose-dependent suppression of PTH release with oxotremorine. The suppressive activity could be antagonized with atropine, suggesting that parasympathomimetic nerval impulses play a suppressive role in the regulation of PTH release. Muscarine-receptors appear to be responsible for this mechanism.
Adenoma↗