SEARCH · Search PubMed

Results for “ATROPINE”

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.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 199 records · Page 11Linked to original sources

PubMed1989

Absence of tachyphylaxis to inhaled atropine in patients with chronic obstructive pulmonary disease.

A multicenter, 14-wk, double-blind, randomized, parallel group study of 60 patients with obstructive lung disease was performed to assess tachyphylaxis with inhaled atropine sulfate versus placebo. Forty patients completed the study; twenty-one were treated with placebo and nineteen were treated with atropine sulfate. Atropine and placebo groups were compared before and after inhaled atropine by spirometry at Weeks zero, 6, and 14. Medication side effects, other medication usage, and symptoms were recorded daily. Comparison of FEV1 response to atropine sulfate from baseline at Weeks zero, 6, and 14 did not show a statistically significant decrease. Inhaled atropine sulfate continued to be an effective bronchodilator in both placebo groups and atropine sulfate groups. There was no evidence of significant tachyphylaxis with atropine. Significant side effects in the atropine group when compared with placebo included dry mouth, dry skin, rapid heart rate, and nausea.

Administration, Inhalation↗

PubMed2006

The effects of beta-blockers on dobutamine-atropine stress echocardiography: early protocol versus standard protocol.

BACKGROUND: To study the effects of Beta-blockers during Dobutamine Stress Echocardiography (DSE) comparing the hemodynamic benefits of an early administration of atropine in patients taking or not Beta-blockers. METHODS: One hundred and twenty-one patients were submitted to dobutamine stress echocardiography for the investigation of myocardial ischemia. The administration of atropine was randomized into two groups: A or B (early protocol when atropine was administered at 10 and 20 mcg/kg/min of dobutamine, respectively) and C (standard protocol with atropine at 40 mcg/kg/min of dobutamine). Analysis of the effects of Beta-blockers was done regarding the behavior pattern of heart rate and blood pressure, test time, number of conclusive and inconclusive (negative sub-maximum test) results, total doses of atropine and dobutamine, and general complications. RESULTS: Beta-blocked patients who received early atropine (Group A&B) had a significantly lower double product (p = 0.008), a higher mean test time (p = 0.010) and required a higher dose of atropine (p = 0.0005) when compared to the patients in this group who were not Beta-blocked. The same findings occurred in the standard protocol (Group C), however the early administration of atropine reduced test time both in the presence and absence of this therapy (p = 0.0001). The patients with Beta-blockers in Group A&B had a lower rate of inconclusive tests (26%) compared to those in Group C (40%). Complications were similar in both groups. CONCLUSION: The chronotropic response during dobutamine stress echocardiography was significantly reduced with the use of Beta-blockers. The early administration of atropine optimized the hemodynamic response, reduced test time in patients with or without Beta-blockers and reduced the number of inconclusive tests in the early protocol.

Adrenergic beta-Antagonists↗

PubMed1986

Atropine blockade of growth hormone (GH)-releasing hormone-induced GH secretion in man is not exerted at pituitary level.

The role of acetylcholine (Ach) in the regulation of human GH secretion was assessed using atropine, which selectively blocks cholinergic muscarinic receptors. Paired tests were performed in seven normal subjects using GH-releasing hormone (GHRH) 1-44 (1 microgram/kg iv), with and without atropine pretreatment (1 mg im). The GHRH 1-44-induced GH secretory peak [20.7 +/- 4.5 (SEM) ng/ml] was completely blocked by atropine administration (2.3 +/- 0.6 ng/ml) (P less than 0.01). To determine whether this atropine blockade was at the pituitary level, a series of in vitro studies were conducted using monolayer cultures of cells from bovine anterior pituitary glands. GHRH 1-44 (10(-8) M) stimulated bovine GH release (11.1 +/- 1.5 micrograms/ml) as compared to control values (5.1 +/- 0.4 microgram/ml) (P less than 0.01). This response was not altered by 10(-6) M atropine (14.9 +/- 0.9 microgram/ml). Similar results were obtained with GHRH, 10(-9) M, with or without atropine, 10(-7) M. Addition of 10(-6) M Ach to the incubation medium significantly increased bovine GH release (12.7 +/- 1.2 microgram/ml) and the effect of 10(-6) M Ach and 10(-8) M GHRH was additive (20.9 +/- 2.1 micrograms/ml) (P less than 0.01). Similar results were obtained with Ach, 10(-5) M, and GHRH, 10(-9) M. Atropine or eserine alone did not alter basal GH secretion, and atropine blocked Ach-stimulating activity. In conclusion, atropine blockade of GHRH-induced GH secretion appears to be exerted at a site other than pituitary.

Acetylcholine↗

PubMed2001

Atropine and bifocals can slow the progression of myopia in children.

BACKGROUND: Atropine 1% ophthalmic solution has been used to retard progression of simple childhood myopia. Problems have been identified in previous studies, including possible observer bias. To address this issue, we evaluated our experience including the duration that atropine maintains a child at 20/30 or better in one spectacle correction compared with controls. METHODS: Fifteen myopic children who received daily atropine 1% ophthalmic solution bilaterally for a mean of 29.3 months (range 3-96) were compared to a control group of 15 unrelated similar myopic patients. The progression of myopia, change of glasses, patient demographics, and any side effects or complaints were recorded. RESULTS: The mean annual myopic progression in the atropine group was 0.05 diopters (D) (+/-0.67) and in the control group 0.84 D (+/-0.26)(P=0.00021). The number of months that vision remained 20/30 or better using the same pair of glasses was 25.1 (+/-19.3) for the atropine group and 13.5 (+/-10.3) for the control group (P=0.049). Mean followup time was 29 months for the atropine group and 42.6 months for the control group. There were no statistical differences between the two groups regarding sex, age, or age at first glasses. CONCLUSIONS: Atropine ophthalmic solution nearly halted myopic progression in this investigation. Patients on atropine remained 20/30 or better with a single pair of glasses significantly longer than the control group. While a larger and better controlled study is desirable, atropine appears to be a viable method to retard myopic progression.

Adolescent↗

PubMed2004

Duration and effect of single-dose atropine: paralysis of accommodation in penalization treatment of functional amblyopia.

BACKGROUND AND PURPOSE: Atropine dilates the pupil and paralyzes the ciliary muscle accommodation, blurring vision, and therefore is an effective penalization of the sound eye in the treatment of functional amblyopia of the other eye. The degree of blur induced is a function of the amount of the patient's uncorrected hyperopia and the distance from the eye of the viewed material or object. Another factor determining effectiveness of atropine penalization is the duration of the effect of the atropine. It is the purpose of this study to investigate these factors. METHODS: Six normal children underwent complete eye exam with cycloplegic refraction several days before deliberate instillation of atropine 1% in the sound, or right eye. Distance and near acuity was then tested after 30 minutes, and on subsequent days. Additional data points were derived by placing known minus lenses in front of the tested eye. In addition, we also studied one successfully treated amblyopic patient when he terminated chronic daily atropine in his normal, sound eye. RESULTS: Atropine initially produced a linear reduction in logMAR acuity (blur) at distance of about 0.2 logMAR lines per diopters of uncorrected hyperopia. The magnitude of the blur was greater for near, but the effect of increased hyperopia was slightly greater for distance measurements. This blurring of acuity lasted just less than 48 hours for normal subjects, and just over 48 hours following prompt cessation of chronic daily atropine in that one subject. Regression formulae were derived relating uncorrected hyperopia and time interval following atropine cessation on distance and near acuity in children of amblyopic age range. CONCLUSION: The degree of penalization is highly dependent on the uncorrected hyperopic refractive error. A significant penalization effect is present only for one day or so. Daily atropine is therefore indicated for penalization. To better tailor penalization therapy to target sound eye acuity blur, these formulae and graphs can be used, specifically, in addition, to determine the amount of deliberate spectacle hyperopic undercorrection to maximize the penalization effect.

Accommodation, Ocular↗

PubMed2005

[Effects of oral clonidine premedication on the heart rate response to intravenous atropine during propofol anesthesia].

BACKGROUND: Propofol induces suppression of the sympathetic nervous activity, and attenuates the heart rate responses to intravenous atropine. Similarly, clonidine suppresses the heart rate response to intravenous atropine under awake and enflurane-anesthetized patients. The purpose of this study is to evaluate effects of clonidine on the heart rate response to atropine under propofol anesthesia. METHODS: Thirty-two adults patients were randomly assigned to one of two groups. Clonidine group (n=16) patients received oral clonidine 5 microg x kg(-1) and famotidine 20 mg, and the control group (n=16) patients received oral famotidine alone 90 minutes before anesthesia. After tracheal intubation, anesthesia was maintained with propofol at the effect site concentration of 3 microg x ml(-1) in air and oxygen using the TCI system. All patients received incremental doses of IV atropine 5 microg x kg(-1) over 5 s at 2-min intervals until heart rate increased > 20 beats x min(-1) from baseline values or until atropine 40 microg x kg(-1) was given. RESULTS: Although heart rate response to atropine 5-25 microg kg(-1) was similar between the two groups, heart rate response to atropine 30 microg x kg(-1) in the clonidine group was smaller than that in the control group (P<0.05). When the atropine 40 microg x kg(-1) was administered, heart rate increased > 20 beats x min(-1) in all patients of the control group, but 62.5% of patients in the clonidine group (P< 0.05). CONCLUSIONS: Oral clonidine premedication attenuates the heart rate responses to IV atropine under propofol anesthesia.

Administration, Oral↗

PubMed2005

[Vasodilation effect of atropine on rat mesenteric artery].

AIM: To study the vasodilation effect of atropine and its mechanism. METHODS: Isometric tension was recorded in isolated rat super mesenteric arteries precontracted by noradrenaline (NE) to study the vasodilation effect of atropine, and to investigate the role of endothelial cell and vascular smooth muscle cell on vasodilation. RESULTS: Atropine was shown to significantly dilate the endothelium-intact and endothelium-denuded arteries precontracted by NE. Nomega-Nitro-L-arginine methyl ester (L-NAME, nitric oxide synthase inhabitor), indomethacin (cyclooxygenase inhibitor), propranolol (general beta adrenoceptor antagonist) and glibenclamide (ATP sensitive potassium channel inhibitor) showed no effect on vasodilation of atropine. Atropine did not affect the concentration-contraction curve of K+. However, atropine suppressed the contraction induced by NE and CaCl2, but not that by caffeine in the Ca+ -free Krebs solution. CONCLUSION: Atropine showed significant vasodilation effect which may derive, in part, from endothelium. Besides, atropine could inhibit the receptor-mediated Ca2+ -influx and Ca2+ -release, which was inferred to the mechanism of atropine on vasodilation.

Animals↗

PubMed1979

The effect of large doses of atropine sulfate on heart rate and blood pressure in rats.

Atropine sulfate causes bradycardia in doses which are greater than the usual anticholinergic doses producing tachycardia (Shucard and Andrew, 1977, Res. Comm. Chem. Path. Pharmacol. 16, 401-410). The present study was designed to evaluate the effects of large doses of atropine sulfate on heart rate and systemic blood pressure in rats. Six groups of urethane anesthetized, male, Sprague Dawley rats (200-450 g) were injected with varying doses of atropine via the jugular vein. Groups I through IV received 5 mg/kg, 20 mg/kg, 40mg/kg and 80 mg/kg, respectively. Group V was bilaterally vagotomized before the injection of 80 mg/kg of atropine. Animals in Group VI were bilaterally vagotomized and pretreated with propranolol-HCl before injection of 40 mg/kg of atropine. Atropine caused a significant (p less than 0.005) dose-dependent reduction in both heart rate and blood pressure. The negative chronotropic property of atropine shown in these experiments is in agreement with recent in vitro and in vitro studies. The cause of bradycardia in these doses appears to be an intrinsic property of atropine rather than being centrally mediated. Possible direct action by atropine on peripheral vascular resistance is discussed.

Animals↗

PubMedDate not supplied

Effect of atropine on tracheal mucociliary clearance and bacterial counts.

The purpose of this study was to determine if atropine, which has been shown to alter mucosal function, prolongs the persistence of inhaled bacteria in the trachea. In conscious sheep, bacterial counts in the trachea were determined by quantitative sterile brush cultures obtained before and serially after a controlled inhalation challenge with an aerosolized solution containing P. hemolytica (10(8) CFU X ml-1). The same animals were studied on two days, once without (control day) and once before and during intramuscular administration of 0.2 mg X kg-1 atropine sulfate at hourly intervals for up to 10 h (atropine day). On the control and atropine days, bacterial counts were zero before, and between 5 X 10(5) and 1.6 X 10(7) CFU X ml-1 immediately after inhalation of P. hemolytica. During the first 2 h after challenge, there was a similar semilogarithmic decline in bacterial counts on the control and atropine days despite the fact that mean tracheal mucociliary transport velocity remained unchanged on the control day, and ranged between 32% and 62% of baseline (p less than 0.05) during the 6-10 h post-drug observation period on the atropine day. However, the time to achieve sterility on the control day was less than or equal to 8 h in all animals, and greater than or equal to 8 h on the atropine day. We conclude that atropine prolongs the persistence of viable bacteria in the trachea. This effect of atropine may be related to an impairment of mucociliary clearance or to other alterations in mucosal function.

Aerosols↗

PubMedDate not supplied

Effect of atropine on experimentally-induced airway obstruction in man.

The effect of pretreatment with inhaled atropine methonitrate 1.5 mg and placebo was compared on standardized inhalation challenges with histamine acid phosphate in normal and asthmatic subjects and with antigen in atopic asthmatics. The response was monitored with measurements of specific airway conductance (sGaw). Challenges were repeated, as often as necessary, to obtain responses whose baseline sGaw after premedication varied by less than 35% within an individual. The anticholinergic effect of atropine 1.5 mg was studied on the methacholine response in all subjects. Atropine inhibited the methacholine response and, therefore, the dose was judged adequate to produce cholinergic blockade in the airways. Similar degrees of bronchodilatation (47-49% increase in sGaw) were found in normal subjects and in non-atopic asthmatics, but greater bronchodilatation was achieved in atopic asthmatics (100% increase in sGaw). Among the asthmatics, the lower the initial sGaw the greater the bronchodilatation with atropine. When prechallenge bronchial tone was comparable within individuals, atropine inhibited the mean histamine response of both normal and asthmatic groups and inhibited the mean antigen response of the atopic asthmatics, whereas placebo had no significant effect. No correlation was found between post-atropine sGaw and the effect of atropine on either histamine or antigen response. In conclusion, atropine is a powerful bronchodilator, particularly in atopic asthmatics with increased bronchomotor tone. Histamine- and antigen-induced bronchoconstriction is inhibited by atropine, but the extent of this inhibition varies between subjects.U

Airway Obstruction↗

PubMed1980

Distention-induced gastrin release: effects of luminal acidification and intravenous atropine.

We evaluated whether gastric distention with saline test meals could release gastrin in healthy subjects and whether luminal acidification or atropine would modify this response. Distention with 700 ml saline adjusted to pH 5.0 led to a significant gastrin response (averaging 9 +/- 3 pg/ml above basal levels during the first 15 min after distention, P less than 0.02), whereas distention with 25 ml saline led to no gastrin release. Distention with 700 ml saline adjusted to pH 2.5 also led to a significant gastrin rise, which was nearly identical to that seen at pH 5.0. A small dose of atropine (2.3 micrograms/kg i.v.) significantly enhanced the gastrin response to 700-ml distention at pH 5.0 (average gastrin rise 20 +/- 3 pg/ml, P less than 0.02 vs. 700 ml without atropine). This enhancement of gastrin release by atropine was not due to changes in intragastric pH, because pH was held constant at 5.0 by in vivo intragastric titration. Enhancement was also not due to greater gastric distention after atropine, because gastric volumes after the 700-ml test meal were similar with or without atropine. Although atropine enhanced distention-induced gastrin release, atropine reduced acid secretion by more than 50% (P less than 0.05). Our findings indicate (a) that gastric distention releases significant amounts of gastrin in healthy subjects; (b) this gastrin response is resistant to inhibition by luminal acidification to pH 2.5 and (c) the gastrin response to distention is enhanced by atropine, suggesting that distention may also activate cholinergic pathways that inhibit gastrin release.

Adult↗

PubMed1994

[Adding atropine improves the diagnostic accuracy of dipyridamole-echo test].

BACKGROUND: The clinical experience with dipyridamole stress echocardiography for the diagnosis of coronary artery disease (CAD) revealed that patients with less severe extent of CAD and limited impairment of coronary reserve are frequently not recognized by the test. Increasing myocardial oxygen consumption adding atropine to dipyridamole may improve the diagnostic accuracy of dipyridamole for the detection of CAD. METHODS: Fifty-two patients (48 men, aged 53 +/- 7 years) underwent a high-dose dipyridamole-echo stress test (0.84 mg/kg over 10 minutes) and coronary arteriography within 15 days from the test. Eighteen out of 52 patients were referred for chest pain; 11 suffered from a previous myocardial infarction (MI) and 23 were studied in the early phase after a first acute MI. Starting after 4 minutes from the end of dipyridamole infusion, atropine was added, in 2 doses of 0.5 mg each, at 1-minute interval in those patients with no echocardiographic evidence of myocardial ischemia after dipyridamole alone. Left ventricular wall motion was analyzed on a 11-segment left ventricular model in a qualitative manner. RESULTS: Dipyridamole-echo stress test was positive in 23/52 (44%) and negative in 29/52 (56%) patients. In these patients atropine was added resulting in an additional echo positivity in 14/29 patients. Coronary arteriography was normal in 6 patients (12%); 1-vessel CAD was diagnosed in 23 (44%), 2-vessel CAD in 13 (25%) and 3-vessel CAD in 10 (19%) cases. The sensitivity for CAD diagnosis was 48% (22/46) for dipyridamole alone and 76% (35/46) for dipyridamole-atropine echo (p < .005), while the specificity was 83% (5/6) and 80% (4/5) respectively. Diagnostic accuracy increased from 52% (27/52) to 75% (39/52) (p < .001). The better diagnostic accuracy of dipyridamole-atropine echo stress test was mainly related to the increased sensitivity of the combined test in patients with 1-vessel CAD (from 39% to 70%) (p < .005). Peak heart rate was significantly higher after the addition of atropine (100 +/- 17 beats/min) compared to basal (64 +/- 10) and dipyridamole (85 +/- 12) in those patients with a positive dipyridamole-atropine echo stress test. No limiting side effects were elicited with the addition of atropine to dipyridamole. CONCLUSIONS: The combination of atropine and dipyridamole induces a chronotropic stress adjunctive to flow maldistribution phenomena that permits to increase diagnostic accuracy of dipyridamole-echo stress test particularly in patients with less severe extent of CAD; it is usually well tolerated and safe and may be considered as a useful procedure for optimizing diagnostic value of dipyridamole-echo stress test.

Aged↗

PubMed1997

[The exercise test with atropine].

BACKGROUND: Exercise testing remains the most accessible and widely used technique for the detection of coronary artery disease (CAD) and for the assessment of its severity. Clinical usefulness of the simple exercise test is limited by poor sensitivity and imperfect specificity. Many patients referred for diagnostic stress testing cannot achieve an adequate increase in heart rate due to lack of motivation, poor physical condition, or medications. Atropine increases the heart rate and therefore myocardial oxygen consumption, and might improve the diagnostic accuracy of exercise testing, either reducing the number of non-diagnostic examinations, or increasing the positivity of the test in patients with non severe coronary disease. METHODS: One-hundred-seventy-two consecutive patients (144 males and 28 females, age 58 +/- 8 years) with suspected coronary artery disease underwent exercise testing and coronary angiography. Exercise testing was considered positive in the presence of ST segment depression > or = 0.10 mV horizontal or downsloping, > or = 0.15 mV upsloping, or in the presence of ST elevation without Q waves. The test was considered negative in the absence of significant ST depression or elevation if the exercise heart rate was > 85% of age-predicted maximum, non-diagnostic if the heart rate was < 85%. In 148 patients (86%) coronary angiography showed CAD (> 70% luminal reduction in at least one major vessel), in 24 patients (14%) non significant CAD or angiographically normal coronary arteries (NoCAD). Exercise testing was positive in 134 patients (78%: 85% in CAD, 33% in NoCAD), negative in 13 patients (8%: 3% in CAD, 38% in NoCAD), non-diagnostic in 25 patients (14%; 12% in CAD, 29% in NoCAD). The sensitivity was 85%, specificity was 38%, and diagnostic accuracy 78%. In the 25 patients with non-diagnostic test (18 CAD, 7 NoCAD) the exercise was repeated 30-90 minutes later, immediately after i.v. injection of 1-2 mg of atropine, and was stopped at the same workload of the index test. RESULTS: The atropine-exercise test was well tolerated and accomplished in all cases. The maximal heart rate (139 +/- 11 vs 121 +/- 11) and the double product (25,308 +/- 4082 vs 22,166 +/- 3569) were significantly greater after atropine. The increase of the maximal heart rate improved the detection of the electrocardiographic signs of exercise-induced myocardial ischemia only in CAD patients. In the 18 CAD patients the atropine-exercise test was positive in 8, negative in 5, non-diagnostic in 5. In the 7 NoCAD patients the atropine-exercise test was positive in 1, negative in 6. The test remained non-diagnostic only in 3% of patients. The sensitivity of the test with atropine was 91%, specificity was 63%, and diagnostic accuracy 87%. CONCLUSIONS: The addition of atropine to exercise testing, which causes further chronotropic stress to the myocardium, is well tolerated and safe, and improves the diagnostic accuracy of the test for the detection of coronary artery disease in patients who cannot achieve an adequate exercise heart rate. The combination with atropine increases the utility and the cost-effectiveness of exercise testing.

Atropine↗

PubMed1987

Cardiovascular and allied actions of xylazine and atropine in the unanaesthetized goat.

The cardiovascular effects of xylazine and atropine, separately and in combination, were studied in goats. Methylatropine was used to distinguish between the central and peripheral effects of atropine. Mean arterial blood pressure and heart rate were recorded, and the sedative effect and changes in respiration and salivation noted. Intravenous infusion of xylazine (2.4-80.0 micrograms/kg) decreased mean arterial blood pressure and heart rate in a dose-dependent manner. Single intravenous injections of both atropine sulphate (0.1 mg/kg) and methylatropine bromide (0.05 mg/kg) increased blood pressure and heart rate. After methylatropine, tachycardia lasted twice as long as after atropine. Following atropinization, a potentiated rise in mean arterial blood pressure was present during the infusion of xylazine (80 micrograms/kg). Xylazine-induced bradycardia was reversed by both atropine and methylatropine. The action of atropine is presumed to be primarily peripheral because of the similar effects with methylatropine. Xylazine-induced sedation was dose dependent. At the highest dose the goats were unable to stand for 30-60 min, respiration became irregular with periods of apnoea, and saliva started to drip a few minutes after infusion without increased salivation. Atropine had no visible effect on the sedation, pattern of respiration or saliva dripping effect of xylazine.

Animals↗

PubMed1998

Nasal atropine sulfate: efficacy and safety of 0.050% and 0.075% solutions for severe rhinorrhea.

BACKGROUND: Anticholinergic agents, specifically the quaternary salt of atropine, are currently being recommended for chronic rhinitis and the common cold. OBJECTIVE: To evaluate the efficacy and safety of 50- and 75-microg doses of atropine sulfate as a nasal spray in perennial allergic rhinitis. METHODS: A placebo-controlled, double-blind study compared 2 doses of atropine nasal spray given 4 times daily for 2 weeks to 45 patients with perennial allergic rhinitis after a 2-week baseline period. RESULTS: Both concentrations of atropine nasal spray improved the severity of rhinorrhea and postnasal drip (P<.001) as reported by patients and physicians. The duration of action in reducing rhinorrhea and postnasal drip for atropine was 2 to 3 hours, compared with less than 1 hour for placebo (P<.01). No difference was noted in efficacy between the 2 atropine doses nor in frequency of adverse events with atropine nasal spray and placebo. CONCLUSIONS: Atropine sulfate, 50 or 75 microg 4 times daily, is effective in reducing rhinorrhea and postnasal drip within 2 weeks and may be an alternative therapy for the rhinorrhea component of rhinitis.

Administration, Intranasal↗

PubMed1991

The pharmacokinetics of atropine and diazepam in sheep: intramuscular co-administration.

The purpose of this study was to determine whether the co-administration of atropine and diazepam affect the rate and extent of absorption of either drug. A triple crossover pharmacokinetic study using adult sheep was conducted. Each of nine animals received single injections of atropine (2 mg), diazepam (10 mg), and a combination of the two compounds weekly over a 3-week period. The combination of the drugs was injected into a single intramuscular site through a specially designed tandem syringe. Blood samples were obtained from time 0 to 300 min post-injection. Serum samples were analyzed for atropine by radioimmunoassay and for diazepam by gas chromatography/mass spectrometry. Pharmacokinetic parameters were evaluated by non-compartmental analysis. The co-administration of atropine and diazepam intramuscularly in sheep caused a delay in the time to reach maximal concentration of atropine. However, at the time when a single injection of atropine reached its maximum serum concentration, 92 per cent of that concentration was reached by atropine in the presence of diazepam. Additionally, no difference was detected in the rate or extent of diazepam absorption when administered intramuscularly in combination with atropine at the same site.

Animals↗

PubMedDate not supplied

Tachykinin receptors mediate atropine-resistant rat duodenal reflex contractions in vivo.

The study aimed to establish the possible role of tachykinins as mediators of atropine-resistant reflex contractions evoked by balloon distension in the proximal duodenum of urethane-anesthetized, guanethidine (34 mumol/kg s.c.)-pretreated rats. Distension of the balloon with a small amount (0.2-0.3 ml) of saline induced the appearance of phasic rhythmic contractions (about 11 mmHg in amplitude) which were promptly suppressed by either atropine (3 mumol/kg i.v.) or hexamethonium (28 mumol/kg i.v.). Despite the continuous i.v. infusion of atropine (2 mumol/h), low-amplitude rhythmic phasic contractions recovered, which were promptly suppressed by hexamethonium, to indicate the involvement of an atropine-resistant excitatory reflex. The amplitude of these atropine-resistant contractions was increased to about 4-5 mmHg by further distension of the balloon (0.4-0.6 ml) : under these conditions, the atropine-resistant contractions undergo a progressive fading. The fading was prevented by i.v. administration of the nitric oxide (NO) synthase inhibitor, L-nitroarginine methyl ester (L-NAME, 55 mumol/h), to provide a suitable baseline (amplitude of contractions was 7-8 mmHg) for studying the effect of tachykinin receptor antagonists. I.v. administration of the selective tachykinin NK2 receptor antagonists, MEN 10,627 (10-100 nmol/kg) and SR 48968 (100-300 nmol/kg) or of the selective NK1 antagonist SR 140333 (100 nmol/kg), at doses which do not affect the duodenal contractions induced by acetylcholine (5.5 mumol/kg i.v.), produced a prompt and long lasting suppression of the atropine-resistant reflex duodenal contractions produced by balloon distension in urethane-anesthetized rats, whilst SR-48965 (300 nmol/kg), the enantiomer of SR-48968 devoid, of NK2 receptor blocking activity, was without effect. I.v. administration of the selective NK1 receptor agonists [Sar9] substance P sulfone and septide or of the NK2 receptor selective agonist, [beta Ala8] neurokinin A(4-10) produced dose-dependent contractions of the duodenum. SR 140333 (100 nmol/kg i.v.) selectively antagonized the duodenal contractions produced by [Sar9] substance P sulfone and septide without affecting those produced by [beta Ala8] neurokinin A(4-10). On the other hand, MEN 10,627 (30-100 nmol/kg i.v.) and SR 48968 (100-300 nmol/kg i.v.) but not SR 48965 (300 nmol/kg i.v.) antagonized, at a comparable extent, duodenal contractions induced by both the selective NK2 and NK1 receptor agonists. We conclude that endogenous tachykinins are involved in mediating atropine-resistant reflex contractions evoked by distension of the rat duodenum in vivo: both NK1 and NK2 receptors are activated by endogenous ligands to produce NANC contractions of rat duodenum in vivo. However, the contractile response to i.v. administered NK1 receptor agonists, [Sar9] substance P sulfone and septide, may involve the release of mediators producing smooth muscle contraction via NK2 receptors.

Analysis of Variance↗

PubMed1991

Effects of atropine treatment on in vitro and in vivo binding of 4-[125I]-dexetimide to central and myocardial muscarinic receptors.

Upregulation of muscarinic cholinergic receptors (mAChR) after chronic atropine treatment has been described previously. The present study was designed to evaluate 4-iodine-125 dexetimide as an agent to determine changes in the number of mAChR. Rats were injected subcutaneously with atropine (500 mg/kg) either once or chronically, once daily for 10 days, and sacrificed 24 h later. In vitro binding assays with 4-[125I]-dexetimide showed significant increases in the number of mAChR in cerebra (21%) and ventricles (45%) after chronic atropine treatment but not after acute treatment. The affinity of binding to cerebral and ventricular mAChR declined after acute and chronic atropine treatment. In vivo studies were carried out involving intravenous injection of 4-[125I]-dexetimide 24 h after atropine treatment. Binding was markedly reduced in the brain and heart. Upregulation of mAChR, as seen in in vitro studies, could not be observed because of the remaining atropine. Occupancy of mAChR by atropine persisted as long as 7 days after one dose. The results of these studies indicate that 4-[125I]-dexetimide binding reflects the effects of atropine on central and peripheral muscarinic cholinergic receptors in vitro and in vivo.

Animals↗