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Atropine as an inhibitor of voluntary ethanol intake in male rats.

A single ethanol injection (2.0 g/kg, i.p.) administered to male rats will reduce voluntary ethanol intake (water vs. ethanol 10%) if tested for 24 hr, 6 days after the injection. Maximal inhibition, when compared to saline-injected controls (S), is seen after ethanol injections (E) once a week for 5-6 weeks. At this maximal inhibition atropine (A) or saline (S) was injected i.p. prior to the voluntary 24 hr intake of ethanol. In experiment 1, the doses 1 and 2 mg/kg were used, and in experiment 2, 4 and 8 mg/kg. Each experiment consisted of groups AE, SE, AS and SS, according to the above descriptions. In group AS, atropine reduced 24 hr voluntary ethanol intake with a maximal effect following the 4 mg/kg dose. In group AE, atropine did not increase the inhibitory effect induced by the ethanol injections. Total fluid intake was not influenced. After the treatment period a continuous choice (water vs. 10% ethanol) was offered for 8 (exp. 1) or 11 (exp. 2) weeks. During these evaluation periods the ethanol intake in group SE was always significantly smaller than the corresponding intake in group SS. In the atropine-injected groups (AE and AS) a similar significant difference in voluntary ethanol intake was observed at the beginning but not at the end of the evaluation periods. At the end of exp. 2 a significantly larger number of muscarinic binding sites was obtained in the cortex but not in the striatum of group SE when compared with groups AS and SS. In group AS a negative correlation was found in the striatum between the ethanol intake recorded after the atropine injection in week 5 and 6 and muscarinic binding sites. Atropine, probably by acting on muscarinic binding sites, seemed to have a specific inhibitory effect on voluntary 24 hr ethanol intake, which was similar to the effect induced by the ethanol injections.

Alcohol Drinking↗

[Study on the therapeutic effect of combined use of obidoxime and atropine with respiratory machine on respiratory muscle paralysis caused by omethoate poisoning of rats].

OBJECTIVE: To examine the therapeutic effect of combined use of obidoxime and atropine with artificial ventilation on respiratory muscle paralysis caused by omethoate poisoning in rats. METHODS: Rats were exposed to 2 times the dose of LD50 omethoate and treated with atropine (10 mg/kg) to counteract cholinergic symptoms. When the rats' respiratory frequency became slower and breathed with difficulty, the trachea intubation and artificial ventilation was carried out. The rats in group A were continuously treated with atropine. The dose of obidoxime for Group B, C and D were 8, 15, 20 mg/kg respectively, given at the same time as artificial ventilation and 1, 2, 3 hours later. The doses of atropine was reduced to 1/3 - 2/3 of the first dose so as to maintain the rats atropinized. If the rat survival was beyond 60 minutes after withdrawal of artificial ventilation, the combined treatment was considered successful. The function of isolated phrenic diaphragm of the rats was observed with MS-302 physiological and pharmacological analysis instrument. RESULTS: None of the rats in Group A was successful after withdrawal from artificial ventilation and the function of phrenic diaphragm appeared poor; whereas > 80% of the rats in B, C, D Group were successful after withdrawal from artificial ventilation in 3 h and the function of phrenic diaphragm remained well. The survival rate in B, C and D groups were higher after withdrawal from artificial ventilation than that in Group A(P < 0.01). The function of phrenic diaphragm in Group B, C and D were gradually decreased after ACh was added into the container. CONCLUSIONS: Combined use of suitable dose of obidoxime and atropine with artificial ventilation for respiratory muscle paralysis caused by omethoate poisoning could promote the recovery of diaphragm function and reduce the death rate in poisoned rats.

Animals↗

Determination of atropine (hyoscyamine) sulfate in commercial products by liquid chromatography with UV absorbance and fluorescence detection: multilaboratory study.

A liquid chromatographic (LC) method with 2 detection systems for determining atropine (hyoscyamine) sulfate in commercial products was tested in a multilaboratory study. Depending on the type of product, sample solutions are prepared in methanol or methanol-water (1 + 1). The standard solution contains about 1.0 mg atropine sulfate/100 mL and is prepared in the same solvent used in sample preparation. LC separations are performed on a 7.5 cm Novapak silica column. The mobile phase is prepared by mixing 970 mL methanol with 30 mL of a 1% aqueous solution of 1-pentanesulfonic acid, sodium salt. Detection is by 2 systems, UV absorbance detection at 220 nm and fluorescence detection with excitation at 255 nm and emission at 285 nm. The injection volume is 100 or 200 microL. The following materials were used for the study: 2 separate samples of tablets labeled to contain 0.4 mg atropine sulfate, 2 separate samples of extended-release tablets labeled to contain 0.375 mg hyoscyamine sulfate, one sample of atropine sulfate injection labeled to contain 2 mg/mL, and one sample of 1% (v/v) atropine sulfate ophthalmic. Eight participants analyzed 2 separate portions of the 6 samples by both detection systems. A ninth participant analyzed the samples in duplicate but only by UV absorbance detection because of the unavailability of a fluorescence detector. The relative standard deviation (RSD) between laboratories ranged from 1.4 to 3.3% for samples of tablets and injections but higher for ophthalmic solutions (5.1-5.2%). A linearity study was conducted in the originating laboratory before the multilaboratory study with 5 solutions ranging in concentration from 0.80 to 1.20 mg atropine sulfate in 100 mL. Average recoveries were 100.0% by UV absorbance detection and 99.9% by fluorescence detection; the RSDs were 1.1 and 1.2%, respectively.

Algorithms↗

Effect of topically administered atropine on tear production in dogs.

Baseline tear production values were established for both eyes of 19 dogs, using the Schirmer tear test. Atropine sulfate, 1% solution, was administered topically in the left eye of each dog once daily for 14 days. Tear production was then determined for both eyes at 15, 30, 60, 120, 180, 240, and 300 minutes, and 3, 6, 9, 12, and 15 days. A final Schirmer tear test reading was obtained for each eye 5 weeks after the last atropine treatment to check for the possibility of prolonged effect. Both eyes had statistically significant (P less than 0.05) decrease in tear production that was most marked at 120 minutes after atropine instillation, then returned to baseline values by 300 minutes after instillation. Although atropine was placed in the left eye only, statistically significant difference was not apparent in Schirmer tear test values between the left and right eyes. Tear production continued to decrease in both eyes over time, becoming statistically significant (P less than 0.05) on day 9. However, on days 12 and 15, tear production in the untreated eye plateaued, but that in the treated eye continued to decrease. Five weeks after the last treatment with atropine, both eyes still had a statistically significant (P less than 0.05) decrease in tear production, although Schirmer tear test values had increased from day-15 values and appeared to be returning to baseline. Association was not evident between age or body weight and magnitude of response to topically applied atropine.

Administration, Topical↗

[Effects of penehyclidine hydrochloride or atropine combined with neostigmine for antagonizing residual neuromuscular block on patient's hemodynamics].

OBJECTIVE: To investigate the effects of penehyclidine hydrochloride(PH)/atropine combined with neostigmine for antagonizing residual neuromuscular block on the hemodynamics. METHODS: Eighty patients with elective upper abdominal surgery were randomized equally into PH group and atropine group. Five minutes after the completion of surgery, PH 0.02 mg/kg (in PH group) or atropine 0.02 mg/kg (in atropine group) in combination with neostigime 0.03 mg/kg were given intravenously to reverse the residual neuromuscular block. The heart rate (HR), mean arterial pressure (MAP) and end-tidal CO(2) pressure (P(ET)CO(2)) were recorded 5 min before anesthesia induction, 1 min before injection and 2, 5, 10, and 15 min after injection, respectively. RESULTS: During the investigation, HR in PH group did not undergo conspicuous changes (P>0.05). HR after the injection was markedly faster than that before the injection in atropine group (P<0.01) and did not recover till 15 min after the injection (P>0.05). MAP and P(ET)CO(2) showed no evident changes and no significant difference was observed between the two groups during the investigation (P>0.05). CONCLUSION: Compared with atropine, PH does not obviously affect HR and BP, but atropine may accelerate HR.

Abdomen↗

[The beginnings of modern biological psychiatry in Hungary: the atropine coma. A historical overview].

In the authors' opinion modern biological psychiatry in Hungary started with the investigations into the biological mechanism of atropine coma therapy. Atropine coma was used in the period between 1950 and 1975 mainly in the treatment of various psychoses and obsessive compulsive disorder. In a previous communication the method, indications and adverse effects of atropine coma were outlined and the professional and broader social reasons for its eventual disappearance were discussed. In this paper the therapeutic effectiveness and research into the biological mode of action of atropine coma are summarized. Although thousands of patients received atropine coma therapy in the United States and in several Central-Eastern European countries including Hungary, this therapeutic modality is hardly ever features even in papers on the history of psychiatry. This is all the more surprising because initial therapeutic results with atropine coma were favourable and it seemed to be a more safe and efficient treatment than the more widely used insulin coma.

Atropine↗

Radioprotectant effects of atropine on small intestinal villous shape.

Previous work has shown that irradiation produces changes in small intestinal villous shape, which can be quantified using a villous scoring system applied to scanning electron micrographs. It has already been shown that reserpine, which, like irradiation, increases gastrointestinal motility, produces a similar type of villous collapse, thereby supporting the theory that this form of injury may not be due entirely to changes in the cryptal epithelial compartment, as has been assumed previously. Atropine, chosen for its ability to decrease gut motility, produces a different form of villous shape change. The aim of the current work was to investigate the ability of atropine to decrease the villous damage caused by irradiation and thereby improve the likely absorptive capacity of the small intestine. The current experiments used crypt counting, qualitative light microscopy and villous scoring techniques. Groups of unirradiated mice examined included baseline controls and those treated with atropine, sham irradiation and a combination of these two schedules. Two irradiated groups were studied, one with and one without atropine treatment. The results show that atropine given with irradiation reduces the extent of the damage to villous shape, implying that the total effect on the neuromuscular tissues is less destructive after the combined treatment. It is also of interest that atropine appears to have an additional radioprotectant effect on the radiation induced crypt depletion, implying that neuromuscular behaviour may influence this compartment, hitherto considered as dependent on epithelial proliferative capacity.

Animals↗

Dose-dependent atropine-induced changes in spontaneous electroencephalogram in human volunteers.

Atropine is an anticholinergic drug used in military medicine as an antidote following exposure to cholinesterase-inhibiting nerve agents. However, atropine causes neuropsychologic effects that impair performance. In the present study, we examined electrophysiologic indices that may accompany performance deficits. Quantitative electroencephalographic (EEG) analyses of changes induced by atropine (1.5, 3.0, and 6.0 mg/70 kg, intramuscularly) were assessed in seven male volunteers in a placebo-controlled, double-blind, cross-over experiment. Spontaneous EEG recordings were obtained from relaxed subjects before, 2 hours after, and 8 hours after atropine. Atropine significantly increased delta power, decreased alpha power, and tended to increase theta power and reduce beta and theta frequency. EEG indices of vigilance were reduced by the drug. Dose-related increases in sedation and dysphoria were obtained; some subjects liked these effects. Together, these findings confirmed that atropine causes dose- and time-related electrophysiologic and subjective effects that predict impaired performance.

Adult↗

A protein kinase C-dependent mechanism(s) is involved in atropine-resistant accumulation of diacylglycerol in rat parotid gland.

We investigated the atropine-resistant accumulation of sn-1,2-diacylglycerol (DAG) on stimulation of 1 microM carbachol (CCh) in parotid acinar cells. CCh-induced DAG accumulation was biphasic, peaking at 5 and 20 min. Atropine inhibited two peaks in a dose-dependent manner, but the first peak was inhibited much more than the second one. Atropine (10 microM) completely inhibited both DAG accumulation and the breakdown of phosphatidylinositol 4-monophosphate and 4,5-bisphosphate (PIP2) 5 min after stimulation with CCh. In contrast, the breakdown of PIP2 at 20 min was completely inhibited by 10 microM atropine, but DAG accumulation was not. This atropine-resistant component at 20 min is significantly inhibited by staurosporine, a protein kinase C inhibitor. These results suggest that atropine-resistant accumulation of DAG at 20 min derives directly from other lipids rather than phosphoinositides and is regulated by a protein kinase C-dependent mechanism(s).

Alkaloids↗

Different effects of atropine and cimetropium bromide on gastric emptying of liquids and antroduodenal motor activity in man.

Atropine (1 mg intravenously) and a new antimuscarinic compound, cimetropium bromide (5 mg intravenously), as well as placebo (physiological saline) were tested for their effects on gastric emptying and antroduodenal motility in healthy humans. In a first single-blind cross-over study, the emptying rate was assessed in 12 subjects by measuring paracetamol absorption. In a second single-blind parallel-group study, antroduodenal motor activity was measured in 20 subjects through four perfused open tip catheters with orifices positioned in the antroduodenal region. Atropine, unlike cimetropium bromide, significantly delayed gastric emptying. Antral and duodenal motility index was reduced significantly by atropine, but not by cimetropium bromide. Heart rate significantly increased only after atropine. Three subjects taking atropine complained of dry mouth and one of blurred vision. In conclusion, the results of these studies show that atropine, unlike cimetropium bromide, strongly inhibits gastric emptying of liquids and reduces antroduodenal motor activity in man.

Adult↗

[Inhibition of histamine liberation with atropine sulfate following administration of d-tubocurarine].

The influence of atropine on the release of histamine following the administration of tubocurarine (Amelizol) was studied in anesthetized monkeys. Four groups were prepared: group (a) was not given atropine sulfate as a premedication and (b), (c) and (d) were given atropine 0.0125 mg/kg, 0.025 mg/kg, 0.05 mg/kg by intramuscular injection 30 min before the first blood sampling, respectively. Tubocurarine was given in a dose 0.5 mg/kg intravenously, to all animals. Blood samples were obtained in cases of the preinjection (control) and 1, 3, 6, 10 and 20 min after injection of tubocurarine. The concentration of histamine in the plasma was measured by a fluorometric method and high speed liquid chromatography. When atropine sulfate was given in doses over 0.025 mg/kg intramuscularly 30 min before the administration of tubocurarine, the release of histamine induced by tubocurarine was inhibited, compared to the findings in the non-pretreated groups. Atropine sulfate probably inhibits histamine release induced by tubocurarine through the mediation of intracellular cyclic GMP and atropine can be used as a premedicant in cases of general anaesthesia.

Anesthesia↗

Halothane anaesthesia and suxamethonium III. Atropine 30 s before a second dose of suxamethonium during inhalation anaesthesia: effects and side-effects.

The protection against bradycardia afforded by atropine given intravenously just prior to a second dose of suxamethonium during halothane inhalation anaesthesia was studied in 100 healthy, adult patients randomly allocated to one of five groups characterized by dosage of atropine. ECG monitoring was continuous, and regular determinations were made of serum potassium, PaCO2, PaO2 and blood pressure. Slowing of the heart rate was seen in more than 50% of patients in each group, but bradycardia (heart rate less than 60 beats/min) was seen only in patients receiving the lowest dose of atropine--0.0075 mg/kg. In the other four groups (atropine 0.01 mg/kg-0.02 mg/kg), bradycardia prophylaxis was effective, but at the cost of serious ventricular arrhythmias in 15% of the patients. The incidence of these arrhythmias seemed to increase with increasing atropine dosage. Marked tachycardia was also seen. Because of the incidence of side effects in this and other studies, no absolute recommendation can be made about suxamethonium bradycardia prophylaxis during halothane inhalation anaesthesia, but our present experience suggests that atropine in a dose not exceeding 0.01 mg/kg, given 30 s prior to a second dose of suxamethonium is best.

Anesthesia, Inhalation↗

Heat exchange through cutaneous vasodilation after atropine treatment in a cool environment.

This report summarizes a tightly controlled laboratory study in which the thermoregulatory effects of an intramuscular injection of atropine sulfate (2 mg) were compared with a placebo injection of sterile saline during exposure to a cool environment. Four subjects were tested during seated cycle exercise at a moderate exercise intensity (55% Vo2 peak) at an ambient temperature of 22 degrees C (37% relative humidity; ambient water vapor pressure 1.0 kPa). Esophageal temperature (Tes), mean weighted skin temperature (Tsk), and forearm sweating rate (ms) were continuously measured during 30 min of rest and 35 min of exercise. Skin blood flow (FBF) from the forearm was measured twice each minute by venous occlusion plethysmography. Whole-body sweating was calculated from weight changes pre- and post-exercise. The expected decrease in whole-body and local sweating rate (-57% and -68%, respectively) occurred in the atropine-treated subjects. By 10-15 min of exercise, dry heat loss (R + C, radiative and convective heat exchange) was significantly elevated from the head, chest, back, arm, forearm, and thigh in the atropine experiments. Core temperature actually decreased 0.2 degrees C (p less than 0.05) in the atropine-treated subjects during exercise as a result of enhanced dry heat exchange. By 25 min of exercise. FBF was 98% (p less than 0.05) greater after atropine treatment. These results show that the peripheral modification of cutaneous blood flow which occurs in atropine-treated subjects is sufficient to markedly alter heat exchange in a cool environment.

Adolescent↗

Oral atropine premedication in infants attenuates cardiovascular depression during halothane anesthesia.

The efficacy of oral atropine premedication in attenuation of the cardiovascular depression associated with halothane anesthesia has not been previously evaluated. A solution containing either oral atropine 0.04 mg/kg (HI), 0.02 mg/kg (LO), or a placebo (NO) was randomly administered to 36 infants 1-6 months old and 36 infants 7-15 months old 30-90 minutes before induction of anesthesia. The onset of action of atropine was approximately 25 minutes after administration as determined by a 15% increase in heart rate (HR) above baseline levels. Heart rate, systolic blood pressure (SBP), and mean arterial blood pressure (MAP) were then measured at 1-minute intervals starting just before induction of anesthesia and continuing until onset of surgical stimulation during anesthesia with halothane (up to 3%), nitrous oxide (60%), and oxygen (40%). In infants 1-6 months old, either dosage of oral atropine preserved HR and SBP as compared with placebo. In infants 7-15 months old, either dosage preserved HR but not SBP. The severity of hypotension was greatest in infants 1-6 months of age given placebos. No significant differences existed between oral atropine 0.04 mg/kg or 0.02 mg/kg in either age range. It is concluded that premedication with oral atropine 0.02 mg/kg is effective in attenuating the cardiovascular depression associated with halothane anesthesia in infants.

Administration, Oral↗

The influence of atropine on the cardiopulmonary effects of a xylazine-ketamine combination in dogs.

The effect of atropine on cardiopulmonary changes induced by xylazine-ketamine anesthesia was studied in 7 male dogs. A consecutive i.v. injection of xylazine (1.1 mg/kg) and ketamine (11 mg/kg) induced an anesthesia of approximately 20 min, and increased PaCO2 but decreased PaO2 and pHa for 20 min. The xylazine-ketamine administration increased heart rate for 5 min, which was followed by a small but significant decrease at 30 min posttreatment. The xylazine-ketamine injection decreased left ventricular and mean aortic pressure for 1 to 2 min. The low pressures returned to normal and became higher than base line levels at 5 min posttreatment. The xylazine-ketamine injection increased peripheral resistance and decreased cardiac output and cardiac index for at least 40 min. An i.v. injection of atropine sulfate (0.04 mg/kg) potentiated the effect of xylazine-ketamine on PaCO2 and PaO2, but did not change the effect of xylazine-ketamine on pHa. The atropine injection did not change the transient low left ventricular and mean aortic pressures immediate after the xylazine-ketamine administration, but did potentiate the duration of the increased heart rate, left ventricular and mean aortic pressures induced by xylazine-ketamine between 5 to 40 min. Atropine did not change the effect of xylazine-ketamine on peripheral resistance. Atropine partially antagonized the effect of xylazine-ketamine on cardiac output and cardiac index. Interpretation of the results indicates that atropine may increase cardiac work and may potentiate the pulmonary effect of i.v. administration of xylazine-ketamine.

Anesthesia, Intravenous↗

[Features of the atropine test in persons of different ages].

The diagnostic value of the atropine test was investigated in 47 essentially healthy men of different age groups (25-39, 40-49 and 50-59 years). The cardiovascular responses were evaluated from ECG recorded continuously for an hour after subcutaneous injection of 1.0-0.1% atropine sulphate. Atropine caused a two-stage effect of the cardiac chronotropic function. The first, bradycarditic, stage was induced by vagal stimulation while the second, tachycarditic, stage was, by contrast, produced by atropine blockade of the acetylcholine effect on M-cholinoreceptors of myocardial cells. The atropine effect was identical in sign in all age groups. However, in the young age group the bradycarditic effect was more distinct and atropine-induced arrhythmias were more frequent. In the 50-59 years subjects the tachycarditic effect grew at a slower rate and the electric systole response to a higher heart rate was less pronounced.

Adult↗

Failure of atropine to inhibit gastrin-17 stimulation of the lower esophageal sphincter in man.

Heptadecapeptide gastrin I (G-17) contrast the lower esophageal sphincter (LES) in man and animals. Previous studies in man found that atropine infusion (12 microgram kg-1hr-1) inhibited the effect of gastrin on the LES, suggesting that this effect of gastrin is mediated by a cholinergic mechanism. Studies in the opossum have not shown similar inhibition. To reevaluate the interaction of atropine and G-17 on the LES, 5 normal males were studied. Submaximal and maximal effective doses of G-17 were used with both atropine infusion (12 microgram kg-1hr-1) and rapid intravenous injection (1 mg). There was a small decrease in basal LES pressure with atropine infusion. However, neither atropine infusion nor rapid intravenous injection inhibited LES stimulation by submaximal and maximal doses of G-17. The results do not support the hypothesis that LES responses to gastrin are mediated by an atropine-sensitive cholinergic mechanism.

Adult↗

Differing effects of spontaneous and atropine-induced variations of vagal tone on atrial refractoriness in the conscious dog.

The effects of spontaneous and atropine-induced variations of vagal tone on atrial refractoriness were studied in the conscious dog with complete atrioventricular block. Atrial rate and vagal tone, assessed with atropine, along with maximal paced atrial frequency were monitored for 90 days after the creation of atrioventricular block. The effects of atropine on maximal paced atrial frequency were also studied over the same period. Atrial rate was initially high and then fell back to values close to preoperative sinus levels. Vagal tone was first low and then rose back to values close to preoperative ones. The time-courses of atrial rate and vagal tone were correlated. The rise in vagal tone was accompanied by a correlated increase in maximal paced atrial frequency and thus a shortening of the atrial effective refractory period. However, atropine never significantly lengthened the atrial effective refractory period. This work clearly demonstrates the consistent shortening effect of vagal tone on the atrial effective refractory period in the conscious dog as well as the still unexplained inability of atropine to offset this effect, which may arise from a two-fold action of atropine on the heart.

Animals↗