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PubMed2006

The effect of transdermal scopolamine on the incidence and severity of postoperative nausea and vomiting in a group of high-risk patients given prophylactic intravenous ondansetron.

Specific risk factors place patients at greater risk for postoperative nausea and vomiting (PONV). Routinely, these patients are treated prophylactically with intravenous (IV) ondansetron or transdermal (TD) scopolamine. No study has examined what effect using a combination of these prophylactic treatments would have on the incidence of PONV in a group of high-risk patients. A total of 56 patients at high risk for PONV were treated prophylactically with IV ondansetron and randomized to receive a TD scopolamine patch or placebo. Demographics, incidence, and severity of PONV and side effects and antiemetic requirements were measured. Nausea was measured using a 0 to 10 verbal numeric rating scale. Descriptive and inferential statistics were used for analysis. No difference in demographics or the incidence of side effects was noted between groups. Patients in the scopolamine group had a lower incidence of PONV (P = .043), longer time to first reported nausea (P = .044), longer time to first episode of emesis (P = .031), and decreased supplemental antiemetic requirements (P = .016) compared with the placebo group. Based on this study, we recommend using a combination of TD scopolamine and IV ondansetron to prevent PONV in patients identified as high risk for PONV.

Administration, Cutaneous↗
PubMed1991

Effects of serotoninergic receptor antagonists and their combination with scopolamine on memory.

Using the method for passive avoidance with punishment reinforcement (step-down), it was found that the serotonin (5-HT)-receptor blockers methergoline, methysergide and ritanserin at a dose of 5 mg/kg b.w. administered i.p. 30 min before the training session as well as the M-cholinergic-receptor blocker scopolamine administered at a dose of 2 mg/kg b.w. 90 min before training impaired acquisition and retention of memory traces. The memory impairment was also manifested by the poor habituation of methergoline- and scopolamine-treated rats placed in an unfamiliar environment. Memory deficit was increased by the combination of methergoline or ritanserin with scopolamine. On multiple administration before training the nootropic drug adafenoxate completely prevented the amnestic effect of the combination methergoline plus scopolamine.

Animals↗
PubMed1990

Interactions between scopolamine and muscarinic cholinergic agonists or cholinesterase inhibitors on spatial alternation performance in rats.

The effects on working memory of the muscarinic cholinergic agonists oxotremorine, arecoline, RS86 and pilocarpine, and the cholinesterase inhibitors physostigmine and tetrahydroaminoacadine were investigated in male F344 rats. Working memory was assessed by behavior maintained under a spatial alternation schedule of food presentation in which the interval between trials was varied from 2 to 32 sec. Under control conditions the percentage of correct responses decreased as the retention interval was varied from 2 to 32 sec. Administered alone the cholinergic agonists oxotremorine (0.01-0.1 mg/kg), arecoline (3-30 mg/kg), RS86 (0.3-3 mg/kg) and pilocarpine (0.3-3.0 mg/kg), and the cholinesterase inhibitors physostigmine (0.01-0.1 mg/kg) and tetrahydroaminoacridine (0.3-3.0 mg/kg) either had no effect on or produced dose-related deficits in working memory and decreases in response rates. The muscarinic antagonist scopolamine (0.1 mg/kg) produced retention interval-dependent decreases in the percentage of correct responding and rates of responding. The cholinergic agonists and tetrahydroaminoacridine failed to reverse the effects of scopolamine. However, physostigmine produced a dose-dependent reversal of the working-memory deficits and response-rate decreasing effects of scopolamine. The present results are consistent with the interpretation that drugs which primarily enhance M2 muscarinic cholinergic transmission are ineffective in enhancing working memory or in reversing scopolamine-induced deficits in working memory.

Animals↗
PubMed1989

Three-years' experience of transdermal scopolamine: long-term effectiveness and side-effects.

A study was carried out in 68 otherwise healthy male naval crew members to assess the long-term effectiveness and side-effects of routine transdermal scopolamine administration for the prevention of seasickness. The transdermal patches were applied to the mastoid process before each sailing and the subjects generally used 2 patches a week. Check-ups were made every 3 months over a period of 3 years. The average reported seasickness severity (on a scale of 0 to 7) after 6 months at sea prior to the administration of transdermal scopolamine was 5.64 +/- 0.11 (mean +/- S.E.M.), in comparison with 3.14 +/- 0.23 post-administration (p less than 0.001). A significant improvement was found in the self-estimated performance at sea whilst receiving the drug: 65.7% +/- 3.38% (mean +/- S.E.M.), compared to 25% +/- 2.24% beforehand (p less than 0.001). Contact dermatitis precluded the use of transdermal scopolamine in 3 (4.4%) subjects. The only other significant side-effect was dryness of mucous membranes. In conclusion, transdermal scopolamine was found to be effective in the prevention of seasickness and improvement of performance at sea during 3 years of follow-up and routine administration of the drug was not complicated either by severe side-effects or by performance disturbances.

Administration, Cutaneous↗
PubMed1989

Behaviour of the genetically hypertensive rats of Koletsky type in holeboard and in elevated plus-maze: effect of scopolamine and nicergoline treatment.

The experiments were performed in the adult normotensive rats of Wistar strain and in the genetically hypertensive rats which were developed by Koletsky (12); both sexes were used. The behavior in control and in Scopolamine and Nicergoline treated rats was traced in the holeboard and in the elevated plus-maze. In the control animals, when compared to the normotensive rats of Wistar strain, the genetically hypertensive rats of both sexes show elevated aversion towards open space and hight in the elevated plus-maze, reduced time spent head dipping in holeboard, reduced rate of habituation of locomotor-exploratory activity, and the elevated total time of locomotor-exploratory activity in holeboard. Scopolamine at dose 0.25 mg/kg b. w. and Nicergoline at dose 4 mg/kg b. w. reduced the aversion towards the open space and hight in elevated plus-maze only in the genetically hypertensive rats of both sexes. Both drug when applied simultaneously show mutual potentiation in the genetically hypertensive rats. Both drugs when applied separately or simultaneously caused elevation of time spent head dipping, i. e., elevation of directed exploration. Nicergoline caused decrease and Scopolamine caused increase of total time of exploratory activity in holeboard. Nicergoline increases the rate of habituation of the locomotor-exploratory activity in the males of normotensive rats and in the genetically hypertensive rats of both sexes. Scopolamine remained without effect in the normotensive rats of both sexes, elevated the rate of habituation in the genetically hypertensive males.

Animals↗
PubMed1985

[Effect of idebenone on scopolamine-induced impairment of short-term memory in rats].

The effects of a novel compound, idebenone [6-(10-hydroxydecyl)-2, 3-dimethoxy-5-methyl-1, 4-benzoquinone] and cholinergic drug on short-term memory (STM) were studied in a delayed alternation task in rats. Rats were initially trained using a delayed alternation task in which a forced run to one arm of a T-maze was followed by a free-choice run. A correct free-choice response was defined as a turn toward the arm opposite to that in the forced run, and was rewarded with food pellets. When the time interval between the forced run and free-choice run was longer than 60 sec, the correct responses decreased by about 30% compared with that in no delay trials. After repeated training of the 60 sec-delayed alternation task, the effect of an anticholinergic drug scopolamine (0.1-0.5 mg/kg, ip) on the delayed alternation task was tested. The drug administered 20 min before the test significantly decreased the correct responses in a dose dependent manner. The effect of scopolamine (0.2 mg/kg, ip) was antagonized by the simultaneous administration of physostigmine (0.05-0.2 mg/kg, ip) in a dose dependent manner. Furthermore, physostigmine (0.1 and 0.2 mg/kg, ip) alone increased correct responses in the same task. Idebenone (3-30 mg/kg, ip), administered simultaneously with scopolamine, significantly improved the scopolamine-induced decrement of correct responses, with the highest efficacy at 10 mg/kg. The compound alone did not affect the number of correct responses. These results suggest that STM is closely related to the cholinergic system, and that idebenone may have an improving effect on the impairment of STM induced by a decreased cholinergic activity.

Animals↗
PubMed1986

Transdermal scopolamine: human performance and side effects.

The effect of transdermal scopolamine on performance was tested on 23 naval volunteers. Performance was evaluated by using a battery of professional (naval-related) and cognitive tests. For all tests performed there were no significant differences between the scores obtained in placebo and transdermal scopolamine conditions. These results were in close agreement with subjective estimations of performance. Transdermal scopolamine significantly reduced salivary flow, whereas mood state, visual acuity, and eye accommodation for near vision were not affected. We conclude that transdermal scopolamine administration is not accompanied by decrement in performance abilities and can safely be used by naval crews.

Accommodation, Ocular↗
PubMed1980

[Inhibitory effect of scopolamine on recent memory of mice].

In this research the Authors have studied the action of scopolamine on the memorization of the explorative behavior of the mice. They gave scopolamine before each of the 2 explorations made at an interval of 24 h one from the other. The results obtained show that in these experimental conditions, scopolamine cancels the short-time memory in a more complete fashion compared to the only administration before the second exploration. The Authors advance the hypothesis that this effect of scopolamine can be in relationship to its action on the cholinergic system.

Animals↗
PubMed1995

[Effects of scopolamine on serotonin in the spinal cord and atria of morphine-dependent rats].

The effects of scopolamine on serotonin (5-HT) in the spinal cord and atria of morphine-dependent rats were studied. Levels of 5-HT and its metabolite, 5-hydroxyindolactic acid (5-HIAA) in the spinal cord and atria were analyzed by HPLC-ECD method. The results showed that contents of 5-HT, 5-HIAA in the spinal cord of morphine-dependent rats were statistically higher than those of controls (P < 0.01, n = 6), and that scopolamine inhibited morphine's effect by decreasing 5-HT, 5-HIAA in the spinal cord. After acute abstinence (1d), the contents of 5-HT in the spinal cord in natural withdrawal group were decreased, but increased in scopolamine group. After chronic abstinence (6d), the contents of 5-HT in the spinal cords in the two groups were all increased to above normal level. The results also showed that scopolamine did not affect the increasing of 5-HT in atria induced by morphine. The data support a role of muscarinic receptor on changes of 5-HT metabolism in the spinal cord in morphine-dependent rats.

Animals↗
PubMed1995

[Effect of scopolamine on morphine levels in serum and urine in rats].

Free morphine and conjugated morphine were determined by radioimmunoassay. Excretion of conjugated morphines in urine was increased significantly by treatment with scopolamine in a dose-related manner in morphine-dependent Sprague-Dawley rats (n = 8). Conjugated morphine in serum was increased by administration of scopolamine greater than that of controls at 2h, and both free and conjugated morphine in serum were enhanced at 24h after last injection of morphine in morphine-dependent rats (n = 6). After use of scopolamine (0.5mg/kg, bid, ip) for 3d the rats (n = 6) received single injection of morphine (10mg/kg, sc), the levels of free morphine were increased greater than those of controls at 2 and 10h. The data showed that scopolamine may not only induced the metabolism of morphine in liver, but also facilitated subcutaneous absorption of morphine, which result in enhancing the excretion of morphine.

Animals↗
PubMed1995

[Use of transdermal scopolamine in the prevention of neuro-cardiogenic syncope induced by the tilt test].

INTRODUCTION AND OBJECTIVES: The underlying mechanism of syncope induced by head-up tilt test is still incompletely understood. It has been proposed a sudden increase in parasympathetic's activity induced by the excessive activation of the cardiac mechanoreceptors. The aim of our study was to evaluate the clinical, electrocardiographic and hemodynamic responses to head-up tilt test before and after treatment with transdermal Scopolamine (anticholinergic agent). METHODS: We studied 17 patients (8 females, 9 males; mean age 43 +/- 19 years) with > or = 2 syncopal episodes of unknown origin and a positive tilt test (a positive response to tilt testing alone or in conjunction with an infusion of isoproterenol was defined as the appearance of syncope or presyncope associated to hypotension and/or bradycardia). Symptoms developed in 12 patients during the baseline tilt (Group I) and in 5 patients after infusion of isoproterenol (Group II). Mean time to symptoms was 8.5 +/- 7.9 minutes in group I. All patients were them treated with transdermal Scopolamine (1.5 mg/24 hours) and 48 hours later tilt test was repeated. RESULTS: In group I, 8 patients (66.6%) became tilt test negative and in the remaining 4 patients mean time before the appearance of symptoms was increased (8.5 +/- 7.9 vs 16.2 +/- 2.5 minutes; p < 0.05). In group II, 3 patients (60%) became tilt test negative and in the remaining 2 patients symptoms developed after an infusion of higher doses of isoproterenol than in the first study. So, with transdermal scopolamine 11 out of 17 patients became tilt test negative and time to symptoms was increased in all of the remaining 6 patients. CONCLUSIONS: Our study suggest that transdermal scopolamine is an usefull treatment in the prevention of neuro-cardiogenic syncope induced by head-up tilt test.

Administration, Cutaneous↗
PubMed1994

A comparison of the efficacy of cinnarizine with scopolamine in the treatment of seasickness.

Scopolamine was compared with cinnarizine in a double-blind sea trial involving 179 subjects from the crews of 2 warships. Medication was initiated prophylactically when weather information indicated the approach of nauseogenic conditions. Ship motion was measured during drug treatment periods. In one ship, moderate to severe nauseogenic conditions were encountered; a parallel group comparison was achieved in this. In the other ship, the motion experienced was of a mild nature; a crossover comparison was achieved. Scopolamine was shown to be more effective than cinnarizine in protecting against the symptoms of seasickness. In mild motion, cinnarizine was better tolerated than scopolamine in having less marked side effects. As motion severity increased, the comparative tolerability of scopolamine improved.

Cinnarizine↗
PubMed1994

Preoperative transdermal scopolamine does not reduce the level of nausea and frequency of vomiting after laparoscopic cholecystectomy.

OBJECTIVE: To determine the efficacy of scopolamine administered transdermally before laparoscopic cholecystectomy as a means of reducing postoperative nausea and vomiting. DESIGN: A randomized, double-blind, placebo-controlled study. SETTING: A tertiary-care, university-affiliated hospital. PATIENTS: A volunteer sample of 125 men and women between 20 and 60 years of age scheduled to undergo elective laparoscopic cholecystectomy. Expectant or nursing mothers were excluded, and 35 patients were excluded from the final analysis because of protocol violations. Forty-three patients received scopolamine and 47 patients received a placebo. INTERVENTION: A skin patch (scopolamine or placebo) was applied behind the right ear on the evening before operation and maintained for at least 24 hours postoperatively. MAIN OUTCOME MEASURES: The postoperative level of nausea assessed by the patient on a visual analogue scale, the frequency of vomiting and the frequency of antiemetic use. RESULTS: There was no significant difference in the level of nausea or in the frequency of emesis or use of antiemetics in the first 24 hours postoperatively between the control and study groups. Furthermore, there was no difference in the overall frequency of side effects. However, visual blurring was experienced by six patients in the study group compared with one in the control group (p = 0.082). CONCLUSION: Scopolamine administered transdermally before laparoscopic cholecystectomy does not reduce the frequency or level of nausea and vomiting postoperatively.

Administration, Cutaneous↗
PubMed1993

(+/-)Baclofen sensitive scopolamine-induced short-term memory deficits in mice.

Possible involvement of GABA receptor systems in scopolamine-induced short-term memory deficits was investigated using latency of mice to reach shock-free zone (SFZ) and number of mistakes (descents) the animal made in 15 min as parameters for acquisition and retention of memory in passive avoidance paradigm. Atropine (1-5 mg/kg), scopolamine (0.1-0.5 mg/kg) but not pirenzepine (5-20 mg/kg) caused disruption of memory. GABA (50, 75 and 100 mg/kg) showed retention enhancing effects in scopolamine-treated and untreated animals but GABA agonist progabide (5-20 mg/kg) did not affect any of the parameter significantly. GABAA agonist, muscimol (0.05 and 0.1 mg/kg) and GABAB agonist, (+/-)baclofen (0.25, 0.5 and 1 mg/kg) and (-)baclofen (0.25 and 0.5 mg/kg) also displayed memory enhancing action. Whereas, GABAA antagonist, bicuculline produced hind limb rigidity, GABAB antagonist, CGP 35348 did not show any effect per se, but reversed the (+/-)baclofen-induced delay in latency, without affecting retention enhancing action of (+/-)baclofen. Combined administration of subeffective dose of GABA (50 mg/kg) and (+/-)baclofen (0.25 mg/kg), showed a significant improvement in acquisition and retention. However, the effect of GABA (100 mg/kg) on acquisition was reversed by bicuculline (2 mg/kg) and by CGP 35348 (100 mg/kg) while improving retention. The present study extends support to the cholinergic concept in cognitive performance and provide an evidence for the influence of GABAergic (particularly GABAB) modulation in scopolamine-induced learning and memory deficits in mice.

Animals↗
PubMed1996

Effects of cholinergic drugs on scopolamine-induced memory impairment in rhesus monkeys.

Rhesus monkeys were trained to perform matching-to-sample responses in which monkeys had to choose one of two stimuli that had the same color as the previously presented sample. Half of a daily session consisted of simultaneous trials where the sample was present during the trial, and the other half consisted of delayed trials, where the sample had been presented at the start of the trial but was withheld at the time of choosing. With vehicle control, the percentage of correct responses (CR%) in both trials exceeded 85%. Scopolamine (4-32 micrograms/kg, SC) selectively decreased the CR% for delayed trials in five out of eight animals, suggesting impairment of short-term memory. Physostigmine (2-16 micrograms/kg, SC), arecoline (16-128 micrograms/kg, SC) and nicotine (4-32 micrograms/kg, SC) attenuated the scopolamine-induced impairment of CR% in delayed trials with concurrent administration with scopolamine. Methamphetamine (16-64 micrograms/kg, SC) did not show such effects. These results suggested that scopolamine-induced memory impairment could be recovered by cholinergic agonists.

Animals↗
PubMed1997

Functional activation of cerebral blood flow abolished by scopolamine is reversed by cognitive enhancers associated with cholinesterase inhibition: a positron emission tomography study in unanesthetized monkeys.

The effects of somatosensory stimulation on the regional cerebral blood flow (rCBF) response were studied in unanesthetized monkeys before and after treatment with scopolamine and three cognitive enhancers (physostigmine, E2020 and tacrine) that inhibit cholinesterase, using 15O-labeled water and high-resolution positron emission tomography. Under control conditions, somatosensory stimulation induced a significant increase in the rCBF response in the contralateral somatosensory cortex of monkey brain. Intravenous administration of scopolamine (50 microg/kg) resulted in abolishment of the rCBF response to stimulation. The rCBF response abolished by pretreatment with scopolamine was recovered by administration of physostigmine (1 or 10 microg/kg), E2020 (10 or 100 microg/kg) or tacrine (100 or 1000 microg/kg), in a dose-dependent manner. The effect of E2020 (100 microg/kg) on the rCBF response lasted for >4 hr, whereas the effects of physostigmine and tacrine were of shorter duration. These findings suggest that these compounds reversed the scopolamine-abolished rCBF response to somatosensory stimulation via enhancement of cholinergic neurotransmission, which was mainly induced by cholinesterase inhibition.

Animals↗
PubMed1997

Systemic administration of atipamezole, an alpha 2-antagonist, can reduce scopolamine-induced hyperactivity in rats.

The present study investigated whether an alpha 2-adrenoceptor antagonist (atipamezole) can influence hyperactivity induced by the systemic administration of scopolamine. In the water maze (WM) task, scopolamine (scop) 0.25 mg/kg treatment significantly increased swimming speed during the acquisition phase of this task. Atipamezole (ati) 30 micrograms/kg slightly reduced swimming speed both in saline- and in scop-treated rats. Ati 300 micrograms/kg slightly reduced swimming speed in saline-treated rats, and it prevented the scop-induced increase in swimming speed, because ati300-scop treated rats swam more slowly than the saline-saline group. In addition, ati 300 micrograms/kg reduced the total distance swum in scop-treated rats during a free swim trial (the platform was removed from the pool) performed 1 day after the acquisition phase of the WM test, even though it did not affect this parameter when administered alone. In the open arena task, which assessed the ambulation of rats when the pool was covered with a solid floor, scopolamine dose-dependently increased locomotor activity. The rats ambulated more when treated with scop 0.50 mg/kg compared to vehicle treatment, whereas the effect of scop 0.25 mg/kg treatment did not reach significance. In a test investigating the effects of ati 300 micrograms/kg and scop 0.50 mg/kg given singly or combined, the rats ambulated more during both ati 300 micrograms/kg and scop 0.50 mg/kg treatments given alone, but when combined, the rats ambulated less than during scop-saline treatment even though this was more than during control (saline-saline) treatment. These results indicate that the systemic administration of an alpha 2-antagonist can reduce hyperactivity induced by scopolamine.

Adrenergic alpha-2 Receptor Antagonists↗
PubMed2006

Comparison of glucagon and scopolamine butylbromide as premedication for colonoscopy in unsedated patients.

PURPOSE: Premedication with glucagon or hyoscyamine is reported to be effective in reducing colonic spasm. However, these drugs can be associated with unfavorable events. This prospective study was designed to compare the effects of premedication with glucagon with those of scopolamine butylbromide on cardiopulmonary parameters, intubation time, and patient discomfort in unsedated patients undergoing diagnostic colonoscopy. METHODS: One hundred consecutive adult patients (65 males) undergoing colonoscopy without sedation were randomized to receive 1 mg of glucagon (n = 50) or 20 mg of scopolamine butylbromide (n = 50), intramuscularly. Physiologic changes, including systolic blood pressure, heart rate, and oxygen saturation, were monitored before colonoscope insertion and at three-minute intervals during colonoscopy. The percentages of completed procedure and time to cecal intubation were recorded. Patients were asked to rate pain by using a five-point pain score (0 = no pain; 4 = severe pain). RESULTS: The percentages of completed procedure (96 vs. 98 percent), time to cecal intubation (16.3 vs. 14.5 minutes), and pain score (1.7 vs. 1.5) did not differ significantly between two groups. An increase in heart rate of more than ten beats per minute from baseline during colonoscopy occurred significantly more often in scopolamine group (44 percent of 50 patients) than in the glucagon group (12 percent of 50 patients; P = 0.0004). There were no significant differences between the two study groups with regard to changes in systolic blood pressure and decrease in oxygen saturation during colonoscopy. CONCLUSIONS: Premedication with 1 mg of glucagon facilitates favorable examination with respect to physiologic changes compared with 20 mg of scopolamine. These features favor glucagon as the preferred premedication for patients undergoing colonoscopy.

Aged↗