Showing papers on "Atropine published in 1982"

Quantitative Evaluation of Cardiac Parasympathetic Activity in Normal and Diabetic Man

Abstract: Heart rate and RR variation (the standard deviation of the mean RR interval for a 5-min period) were evaluated as measurements of cardiac parasympathetic nervous system activity in fasting supine diabetic (N = 22) and comparable age normal (N = 22) subjects. The rate of breathing did not effect heart rate, but was inversely related to the RR variation (r = 0.89, P less than 0.01). Heart rate was increased (P less than 0.0001) and RR variation decreased (P less than 0.05) during beta-adrenergic stimulation with isoproterenol and during parasympathetic blockade with atropine (both P less than 0.0001). Hence, the cardiac effects of beta-adrenergic stimulation may mimic the effects of diminished parasympathetic function. To evaluate parasympathetic control of RR variation, independently of possible effects of increased sympathetic activities, studies were performed during beta-adrenergic blockade with propranolol. RR variation during propranolol was less both in 14 diabetic subjects without clinical symptoms of autonomic neuropathy (P less than 0.005) and in 8 diabetics with clinical symptoms of autonomic neuropathy (P less than 0.001) when compared with 22 age-comparable normal subjects. The measurement of RR variation was very reproducible with a day-to-day coefficient of variation of 9.7 +/- 2.8% (x +/- SEM) in diabetic subjects with stable hyperglycemia. It is concluded that supine RR variation during a deep respiratory rate and during beta-adrenergic blockade is a sensitive, quantitative, and reproducible method to evaluate parasympathetic nervous activity in normal and diabetic subjects. Furthermore, cardiac parasympathetic activity may be diminished in diabetic subjects before clinical symptoms of autonomic neuropathy are evident.

Receptors on smooth muscle cells: characterization by contraction and specific antagonists

Abstract: Smooth muscle cells were isolated from the stomach of the guinea pig, and the kinetics, stoichiometry, and specificity of contraction in response to the C-terminal octapeptides of cholecystokinin (CCK-OP), gastrin-17, and acetylcholine were examined. All three agonists elicited dose-dependent peak contraction that did not depend on the presence of extra-cellular calcium. The potencies of CCK-OP and gastrin-17 were equal (D50, 10(-11) M) and 10 times greater than the potency of acetylcholine (D50, 10(-10) M). A combination of low doses of acetylcholine and CCK-OP was synergistic; however, its effect did not exceed the maximal responses to either agonists alone or to high extracellular concentrations of calcium. The specificity of the receptors was established by the use of atropine and the two CCK-receptor antagonists dibutyryl cGMP and proglumide. The span of the dose-response curves was wide, suggesting the existence of receptor heterogeneity. It is concluded that gastric smooth muscle cells of the guinea pig possess distinct, high-affinity receptors for CCK-gastrin and acetylcholine; the receptors mediate contraction that is not immediately dependent on the presence of extracellular calcium.

Muscarinic agonists inactivate potassium conductance of guinea‐pig myenteric neurones.

Abstract: 1. The effects of muscarinic agonists applied both by perfusion and ionophoresis to myenteric neurones of the guinea-pig ileum were investigated by intracellular recording methods. 2. Perfusion with muscarinic agonists (acetylcholine, oxotremorine, methacholine, bethanechol) in concentrations of 100 nM to 10 microM caused membrane depolarizations. Brief ionophoretic applications of oxotremorine, or acetylcholine in the presence of hexamethonium, evoked depolarizations with a latency of 100 ms to 1 s and a duration of 5-60 s. 3. The depolarizations were completely antagonized by low concentrations (1-10 nM) of the muscarinic antagonists hyoscine or atropine. 4. The latency and time course of the muscarinic depolarizations were about one thousand times longer than those of nicotinic responses evoked in the same cell by acetylcholine applied from the same ionophoresis electrode. 5. The muscarinic depolarization was associated with a conductance decrease and reversed polarity at a membrane potential close to the potassium equilibrium potential. 6. The muscarinic depolarization became smaller but did not disappear completely during prolonged (up to 60 min) perfusion or repeated (more than 0.02 Hz) ionophoretic applications of muscarinic agonists. 7. Lower concentrations (3-30 nM) of oxotremorine, which did not change membrane potential, reduced the amplitude and duration of the calcium-dependent increase in potassium conductance which follows a burst of action potentials. 8. It is concluded that the muscarinic depolarization of myenteric neurones is due to potassium inactivation.

The effect of nicotinic and muscarinic receptor blockade on cholera toxin induced intestinal secretion in rats and cats.

Abstract: The effects of hexamethonium (cholinergic nicotinic receptor antagonist) and atropine (cholinergic muscarinic receptor antagonist) on cholera toxin induced secretion were investigated in denervated segments of the small intestine of rats and cats. While there was no effect of atropine, hexamethonium markedly inhibited choleraic secretion and turned it into a net fluid absorption in many animals. This observation further strengthens our hypothesis that the enteric nervous system is involved in cholera secretion.

The effects of atropine on [3H]acetylcholine secretion from guinea-pig myenteric plexus evoked electrically or by high potassium

Abstract: 1. The myenteric plexus-longitudinal muscle preparation of the guinea-pig ileum was incubated with [(3)H]choline (1.125-1.5 muM), and then superfused with Tyrode solution containing hemicholinium-3 (10 muM). Secretion of [(3)H]acetylcholine ([(3)H]ACh) was evoked either (a) by electrical field stimulation (0.5-15 Hz, 150 shocks per period, 0.5 msec), used to ;indirectly' depolarize the varicosities of nerve terminals, or (b) by high potassium (40 mM with 1 muM-tetrodotoxin, for 6 min, or 80 mM without tetrodotoxin, for 1 min), to ;directly' depolarize varicosities.2. With these stimulation parameters, which yielded about the same fractional secretion of [(3)H]ACh, and with eserine (10 muM) present in the medium, atropine (1 muM) enhanced the ;indirectly', electrically evoked secretion 3.65+/-0.34 (n = 6) fold, and that caused by 40 mM or 80 mM-potassium 1.82+/-0.06 (n = 6) or 1.55+/-0.09 (n = 10) fold, respectively. Atropine thus enhanced ;indirectly', electrically evoked secretion 4-fold more than that caused by ;direct' depolarization of varicosities with high potassium (P < 0.001).3. This difference is not likely to be caused by depression of the sensitivity of the presynaptic muscarinic receptors to ACh released by nerve stimulation, caused by the hypertonicity of the medium in the potassium stimulation experiments. The medium made hypertonic by addition of Tris-HEPES (80 mM) did lower the binding affinity of membrane preparations of (pre- and post-synaptic) muscarinic receptors, to carbamylcholine, and also the contractile responsiveness of the longitudinal muscle to this agent, in both cases to about one half. But it did not appear to alter the responsiveness of either pre- or post-synaptic muscarinic receptors to endogenous ACh, released by nerve stimulation.4. The results support a dual-mode model for the muscarinic negative feed-back control of ACh secretion from the nerve terminals of this preparation, mainly operating by restriction of the invasion of terminals, and only secondarily by depression of the efficiency of depolarization-secretion coupling in invaded varicosities.5. Since this model has earlier been proposed to apply for the control of secretion of [(3)H]noradrenaline from the micro-anatomically similar nerve terminals of noradrenergic nerves, the present findings suggest that the model may have a wider biological significance, and possibly apply to the control of the secretory activity of boutons-en-passant nerve terminals in general.

Pharmacokinetic Studies on Atropine with Special Reference to Age

Abstract: Pharmacokinetic studies on atropine were performed in 52 patients under general or spinal anaesthesia. Age had a clinically significant effect on the kinetics of this alkaloid: in children under 2 years of age and in the elderly a prolonged elimination was found. This might explain, partly at least, the higher sensitivity of these age groups to the effects of atropine. Age had no effect on the serum protein binding of this alkaloid. Atropine was found in human CSF after a single i.m. administration, but not after a single i.v. administration. During anaesthesia after i.v. atropine administration, a diminished cardiovascular response was found in the elderly in comparison with healthy adult patients. This indicates changes also at the cholinergic receptor sites in the elderly.

VIP as a mediator of hexamethonium-sensitive, atropine-resistant vasodilation in the cat tongue.

Abstract: Electrical stimulation (10 V, 0.2 ms) of the chorda-lingual nerve caused a biphasic vasodilatory response in the cat tongue with an initial phase which was most marked at low frequencies and a maintained phase which increased with frequency. Simultaneously, there was a VIP release as indicated by a marked increased VIP output from the tongue. VIP output increased with time of stimulation and was most pronounced at high frequencies. Atropine abolished the initial phase of vasodilation at low frequencies as well as reduced this phase at medium frequencies. At high frequency stimulation (15 Hz), the vasodilation was still somewhat reduced by atropine but in contrast to the cat submandibular salivary gland, the duration of the vasodilatory response did not increase after atropine. Furthermore, atropine did not increase VIP output from the tongue during nerve stimulation. Hexamethonium completely abolished VIP release as well as most of the vasodilation upon stimulation of the chorda-lingual nerve. The remaining vasodilation may be due to antidromic stimulation of unmyelinated trigeminal sensory neurons, since it was present when using high threshold stimulation parameters (10 V, 5 ms). Local intra-arterial infusion of acetylcholine or VIP caused a marked vasodilation of the tongue. Also substance P infusion induced a vasodilatory response. The response to acetylcholine was atropine sensitive, while the effects of VIP and substance P were atropine-resistant. Combined infusions of VIP and acetylcholine had an additive effect on vasodilation. In conclusion, the present data suggest that low threshold chorda-lingual nerve stimulation induced a release of both acetylcholine and VIP from postganglionic neurons in the tongue. The contribution by these two agents in the vasodilatory response may then depend upon time and frequency of stimulation. In contrast to the VIP nerves in the submandibular gland, no evidence suggests that VIP release from vascular nerves in the tongue is affected by atropine. High threshold stimulation also induces antidromic vasodilation possibly mediated via substance P release.

Plasma Pharmacokinetics of Intravenously Administered Atropine in Normal Human Subjects

Abstract: The pharmacokinetics of atropine (dl-hyoscyamine) was studied in six normal volunteers following a single 1-mg intravenous dose of atropine. Atropine plasma levels were collected for 24 hours and analyzed by radioimmunoassay. Pulse rates were monitored and compared with predose values in each subject. Atropine plasma concentrations were fitted by least-squares regression analysis. The observed maximal increase in pulse rate, at 12 to 16 minutes after the dose, correlated with the maximum predicted tissue levels of atropine based on the computer fit of the plasma atropine concentration-time data. No correlation between the time of maximum response and atropine plasma concentrations was observed. The average half-life of atropine was 4.125 hours. This data may be used to design a multiple-dosing regimen for intravenous atropine in patients.

Characterization of bombesin effects on canine gastric muscle.

Abstract: Synthetic bombesin increased the frequency and amplitude of spontaneously occurring contractions of muscle strips from antrum and corpus of the canine stomach in vitro. The effect of bombesin on frequency of contractions in this system was myogenic; was unrelated to receptors for acetylcholine, norepinephrine, substance P, or cholecystokinin; and was independent of extracellular calcium. The effect of bombesin on the amplitude in the circular muscle was unaffected by tetrodotoxin and atropine but locked by verapamil, whereas in the longitudinal muscle it was blocked by tetrodotoxin and atropine. In the circular antral muscle bombesin was approximately 100,000 times more potent than acetylcholine at threshold concentrations and was equipotent to cholecystokinin. The high potency of bombesin and its known presence in gastric nerve fibers make it a candidate for a neurotransmitter function in regulation of gastric mobility.

The effects of substance P and met5-enkephalin in dog ileum.

Abstract: Substance P initiated tonic contraction of dog ileum when administered in doses from 1 pg to 20 μg intraarterially (ED50 = 67 ng). Low doses acted to excite cholinergic postganglionic neurones since atropine or tetrodotoxin (TTX) increased the ED50 of substance P about 25-fold, while hexamethonium and local field stimulation had only a small effect to increase the ED50. Also atropine and tetrodotoxin effects were not additive. Higher doses apparently acted to stimulate smooth muscle directly, but no evidence was obtained that local field stimulation could release substance P to act on smooth muscle. Substance P tachyphylaxis prevented substance P actions on cholinergic nerves, but it did not affect responses to intraarterial acetylcholine or block distal inhibition from proximal distention or field stimulation. Met-enkephalin given intraarterially, was also excitatory in doses from 1 ng to 20 μg; the amplitude of tonic and phasic contractions produced was significantly decreased by TTX and atropine but wa...

Effect of the H1 antihistamine chlorpheniramine maleate on histamine-induced symptoms in the human conjunctiva. Indirect evidence for nervous H1 receptors

Abstract: Earlier studies have shown that intranasal chlorpheniramine (0.77%) can inhibit histamine-induced tickling, sneezing, and hypersecretion by a local effect on nerve fibres. The aim of the present study was to examine whether this solution had local anaesthetic of parasympatholytic properties. If neither of these properties are present it suggests that the anti-pruritic effects of the solution are caused by inhibition of H1 receptors, which in turn is indirect evidence for the presence of H1 receptors on nerve fibers. In a double-blind design 15 normal subjects were provoked with histamine in the eye after pretreatment with chlorpheniramine or with a local anaesthetic, oxybuprocain. Both drugs inhibited itching, but the H1 antihistamine was significantly more effective than the local anaesthetic (P less than 0.01). Corneal sensitivity was measured by an esthesiometer, and pupil difference was used as a measure for atropine activity. Chlorpheniramine had neither a local anaesthetic nor a parasympatholytic effect. This study has therefore strengthened the hypothesis that there are nervous H1 receptors in the mucous membranes of the eye and airways and has extended its application in animals to also include man.

Cholinergic Cerebral Vasodilatation in the Rabbit: Absence of Concomitant Metabolic Activation

Abstract: Cerebral blood flow (CBF) was estimated from measurements of internal carotid blood flow and sagittal sinus blood flow in mechanically ventilated rabbits under 70% N2O–30% O2. Intravenously administered physostigmine, a cholinesterase inhibitor, increased CBF under normocapnia and enhanced the cerebral vasodilatation of hypercapnia, but did not alter the cerebral metabolic rate of oxygen (CMRO2). The cerebrovascular effects of physostigmine were antagonized by atropine but not by dihydro-beta-erythroidine, a nicotinic blocker. Neostigmine, a quaternary cholinesterase inhibitor that does not cross the blood-brain barrier, showed no cerebrovascular effects, It is concluded that the cholinergic cerebral vasodilatation does not depend on cerebral metabolic activation, and that the cholinergic receptors involved are muscarinic and located beyond the blood-brain barrier.

α1‐ADRENOCEPTOR ACTIVATION CAN INCREASE HEART RATE DIRECTLY OR DECREASE IT INDIRECTLY THROUGH PARASYMPATHETIC ACTIVATION

Abstract: 1 The chronotropic effects of alpha- and beta-adrenoceptor agonists were investigated in the pithed rat. 2 The beta-adrenoceptor agonist, isoprenaline, produced only a positive chronotropic response. alpha 1-Adrenoceptor agonists, phenylephrine and amidephrine, produced positive and negative chronotropic effects. Part of the response to phenylephrine was beta-mediated. 3 A positive chronotropic response to amidephrine and phenylephrine was mediated directly through cardiac alpha 1-adrenoceptors and had a different time course from beta-adrenoceptor-mediated responses. 4 A negative chronotropic response to alpha-agonists was potentiated by neostigmine and blocked by atropine, tetrodotoxin or hexamethonium as well as by alpha 1-adrenoceptor antagonists. This may indicate alpha 1-adrenoceptors on preganglionic parasympathetic nerves, stimulation of these receptors causing release of acetylcholine. 5 The alpha 2-adrenoceptor agonist, xylazine, produced a direct negative chronotropic effect on the heart, independent of alpha-adrenoceptors. No evidence was found for functional post-junctional alpha 2-adrenoceptors. At high doses xylazine stimulated cardiac alpha 1-adrenoceptors.

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.

A Comparison of Atropine and Glycopyrrolate in Anaesthetic Practice

Abstract: The two anticholinergics, atropine and glycopyrrolate, were used for premedication and as an adjunct to reversal of residual neuromuscular block in a double-blind study. Glycopyrrolate, being about twice as potent as atropine in the clinical situation, was used in half the dosage of atropine. When used for premedication, no difference was found between the drugs concerning patients complaining of dry mouth, but more patients in the glycopyrrolate group had a gastric juice pH greater than 2.5 compared to the atropine group (not statistically different). The reversal mixture consisted of necostigmine 2.5 mg with either atropine 1 mg or glycopyrrolate 0.5 mg. The heart rate response between 2 and 10 min after injecting the reversal mixture was statistically significant (P ranged from 0.0001 to 0.05), the atropine group showing the most marked decrease: 18% in the atropine group had sinus bradycardia compared to 5% in the glycopyrrolate group: 34% in the atropine group exhibited arrhythmias compared to 10% in the glycopyrrolate group, the most common form being a nodal rhythm in both groups. More patients in the atropine group had "excessive" oropharyngeal secretions (more than 2 ml) when extubated (P less than 0.05). The postoperative assessment showed little difference in the two groups, apart from a lower incidence of nausea and vomiting in the atropine group (not statistically different). The study shows that the use of glycopyrrolate was associated with a more stable cardiovascular system, fewer arrhythmias and superior control of oropharyngeal secretions at the time of reversal.

A study of glycopyrrolate and atropine in the suppression of the oculocardiac reflex during strabismus surgery in children

Abstract: Glycopyrrolate 5 and 7.5μgkg and atropine 10 and 15μgkg were studied in 80 paediatric patients to assess more fully the dose of glycopyrrolate required for adequate prevention of the oculocardiac reflex. A dose-related improvement in protection from this reflex was seen with both drugs, but neither drug prevented reductions in heart rate in every patient. A nodal rhythm was the most common arrhythmia observed with both drugs. In the doses used, no adverse effects were noted and no further anticholinergic treatment was required during muscle traction. Higher doses may be associated with an increase in side-effects with more pronounced dryness of the mouth and tachycardia and, with atropine, a greater likelihood of the production of the "central anticholinergic syndrome"

Effect of cholinergic drugs on acute and chronic morphine dependence.

Abstract: The effect of both centrally and peripherally acting cholinergic drugs on acute and chronic morphine dependence was investigated. The quaternary ammonium drugs, neostigmine and atropine methyl bromide which cross the blood-brain barrier with difficulty, significantly altered the withdrawal jumping and wet shakes in a similar manner to that exhibited by centrally acting tertiary drugs viz. physostigmine and atropine sulphate. The cholinergic agonists inhibited the withdrawal signs while the antagonists enhanced the same. This suggests that the peripheral cholinergic mechanisms are also involved apart from the central mechanisms in the phenomena of acute and chronic morphine dependence.

Dose-response effects of atropine on thermal stimulus-response relationships in asthma.

Abstract: To determine how cholinergic blockade modifies the stimulus-response relationships to thermal provocations, we had seven asthmatics perform increasing levels of eucapnic hyperventilation of subfreezing air (-10.6 +/- 1.9 degrees C) after pretreatment with aerosols of saline and atropine in doses of 0.25, 0.5, 1.0, 3.0, and 6.0 mg. Testing was performed on 5 separate days with both placebo and a single dose of drug. In control experiments, increasing ventilation produced a progressive decrease in the 1-s forced expiratory volume in a stimulus-response fashion. There were no significant differences between any placebo study. Atropine pretreatment did not abolish the obstructive response to airway cooling at any dose but, rather, shifted the stimulus-response curve to the right, so that the effects of muscarinic blockade could be overcome by increasing the stimulus. There were no significant differences between the results observed with 0.25 or 6 mg of atropine. These data demonstrate that cholinergic mechanisms play, at best, a very minor role in exercise-induced bronchospasm and offer a unifying explanation for the disparate findings in the literature regarding antimuscarinic agents in this condition.

Advantages of glycopyrrolate over atropine during reversal of pancuronium block

Abstract: Atropine 0.015 mg kg-1 and glycopyrrolate 0.0075 mg kg-1 were compared as antimuscarinic agents during reversal of pancuronium block with neostigmine 0.03 mg kg-1 in 30 patients anaesthetized with thiopental - N2O- fentanyl and undergoing minor surgery. The decrease of heart rate was more pronounced in patients who received atropine-neostigmine. The mean of the lowest heart rate was 44.3 beats min-1 in the atropine group compared with 54.3 beats min-1 in the glycopyrrolate group. Five patients with atropine-neostigmine developed a transient nodal rhythm as compared with two of those receiving glycopyrrole-neostigmine (non-significant difference). Recovery from anaesthesia, as assessed by the awakening after the discontinuation of N2O administration, was more rapid in patients given glycopyrrolate. In conclusion, glycopyrrolate seems to have advantages over atropine when used during reversal of pancuronium block with neostigmine.