Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “SCOPOLAMINE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

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

At least 37 records · Page 2Linked to original sources
PubMed1997

NTP Toxicology and Carcinogenesis Studies of Scopolamine Hydrobromide Trihydrate (CAS No. 6533-68-2) in F344 Rats and B6C3F1 Mice (Gavage Studies).

Scopolamine hydrobromide trihydrate is used in ophthalmic preparations and as a preanesthetic sedative. Its major use is in transdermal patches for the treatment of motion sickness. Scopolamine hydrobromide trihydrate was selected for study because of considerable human exposure resulting from its use in prescription and over-the-counter preparations. Scopolamine was a suspect carcinogen because it contains an aliphatic epoxide moiety which may act as a biological alkylating agent. Male and female F344/N rats and B6C3F1 mice received scopolamine hydrobromide trihydrate (89% pure) in distilled water by gavage for 16 days, 14 weeks, or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, cultured Chinese hamster ovary cells, and mouse peripheral blood erythrocytes. 16-DAY STUDY IN RATS: Groups of five male and five female rats were administered 0, 75, 150, 300, 600, or 1,200 mg scopolamine hydrobromide trihydrate/kg body weight in distilled water by gavage for 16 days. All rats survived to the end of the study. The final mean body weights and body weight gains of males receiving 600 and 1,200 mg/kg and the mean body weight gain of males receiving 300 mg/kg were significantly lower than those of the control group. Clinical findings included bilateral pupillary dilation in all dosed animals and red eyelids in males and females receiving 1,200 mg/kg. There were no significant treatment-related gross or microscopic lesions. 16-DAY STUDY IN MICE: Groups of five male and five female mice were administered 0, 150, 250, 450, 900, or 1,800 mg scopolamine hydrobromide trihydrate/kg body weight in distilled water by gavage for 16 days. One male and two females receiving 1,800 mg/kg and one female receiving 150 mg/kg died during the study. The final mean body weights and body weight gains of dosed mice were similar to those of the control groups. Clinical findings related to scopolamine hydrobromide trihydrate administration included bilateral pupillary dilation and squinting in all dosed males and females. The relative liver weights of males receiving 1,800 mg/kg and of females in all dosed groups were significantly greater than those of the control groups. There were no significant treatment-related gross or microscopic lesions. 14-WEEK STUDY IN RATS: Groups of 10 male and 10 female rats were administered 0, 15, 45, 135, 400, or 1,200 mg scopolamine hydrobromide trihydrate/kg body weight in distilled water by gavage for 14 weeks. One female receiving 45 mg/kg, one male and one female receiving 135 mg/kg, six males and one female receiving 400 mg/kg, and eight males and seven females receiving 1,200 mg/kg died during the study. The final mean body weights and mean body weight gains of all dosed males and females were significantly lower than those of the control groups. Clinical findings included bilateral pupillary dilation in all dosed males and females and reddening of the eyes in 15 mg/kg males and 135, 400, and 1,200 mg/kg males and females. Hematocrit, hemoglobin concentration, and/or erythrocyte count in male and female rats receiving 45 mg/kg or greater were slightly higher than those of the control groups. In general, these changes were most prominent in rats in the 400 and 1,200 mg/kg groups. Higher hematocrit, hemoglobin concentration, and erythrocyte count were likely due to hemoconcentration from dehydration (relative erythrocytosis). A minimal to mild mature neutrophilia, evidenced by higher segmented neutrophil numbers than in the control group, occurred in all dosed male rats. Sperm morphology and vaginal cytology parameters in dosed rats were similar to those in the control groups. Nine male and five female dosed rats died from esophageal obstructions consisting of feed and bedding material in the posterior pharynx. Tracheal obstruction occurred concurrently with esophageal obstruction as a result of food build-up in the oropharyngeal region. This condition is considered to be secondary to the inhibitory effects of scopolamine hydrobromide trihydrate on salivary gland secretions and on esopon esophageal smooth muscle involved in swallowing. There were no other significant treatment-related gross or microscopic findings. 14-WEEK STUDY IN MICE: Groups of 10 male and 10 female mice were administered 0, 15, 45, 135, 400, or 1,200 mg scopolamine hydrobromide trihydrate/kg body weight in distilled water by gavage for 14 weeks. One male receiving 135 mg/kg and two males and one female receiving 1,200 mg/kg died during the study. The final mean body weights and mean body weight gains of all dosed male groups and females receiving 45 mg/kg and above were significantly lower than those of the control groups. Clinical observations included bilateral pupillary dilation, hyperactivity, and hypoactivity. A minimal to mild mature neutrophilia, similar to that which occurred in the 14-week rat study, occurred in male mice receiving 45 mg/kg or greater. As in the rat study, there was no microscopic evidence of inflammation that could account for the neutrophilia. The estrous cycle length of 1,200 mg/kg females was significantly greater than that in the control group. There were no significant treatment-related gross or microscopic lesions. 2-YEAR STUDY IN RATS: Groups of 60 male and 60 female rats were administered 0, 1, 5, or 25 mg scopolamine hydrobromide trihydrate/kg body weight in distilled water by gavage for 104 weeks. Ten males and ten females from each dose group, excluding the 1 mg/kg female group, were evaluated at 15 months. Survival, Body Weights, Clinical Findings, and Ophthalmic Examination Findings: The survival rates of female rats receiving 1 and 25 mg/kg were significantly lower than that of the control group. Mean body weights of 1 and 5 mg/kg males and females were similar to those of the controls throughout the study. However, mean body weights of 25 mg/kg males and females were generally lower than those of the control groups after about week 25. Clinical findings included bilateral pupillary dilation in all dosed males and females. Ophthalmic examination revealed no significant findings. Hematology: Compared to controls, hematocrit was slightly higher in the 25 mg/kg male rats, similar to the effects observed in the 14-week study; this is consistent with dehydration resulting in hemoconcentration. Reticulocyte numbers in the 25 mg/kg female rats were slightly lower than those in the controls. This result is consistent with the lower body weights, and thus a decreased nutritional status, exhibited by these animals. Plasma Scopolamine Determinations: The serum scopolamine concentrations were 6 ng scopolamine/mL serum for the 5 mg/kg female sample and 12 and 28 ng/mL for the 25 mg/kg male and female samples, respectively. The amounts of scopolamine in the other serum samples were below the minimum detection limit (4 ng/mL) of the analysis method. Neurobehavioral Findings: Horizontal motor activity of 25 mg/kg females was significantly greater than that of the control group on days 90, 180, and 360. Startle response of 5 and 25 mg/kg females was significantly lower than that of the control group on day 90. On day 180, passive avoidance of 25 mg/kg males was significantly lower than that of the control group. Pathology Findings: The incidences of adenoma of the pituitary gland pars distalis decreased with increasing dose in both male and female rats; however, this trend was only significant in males (males: vehicle control, 19/49; 1 mg/kg, 17/49; 5 mg/kg, 13/50; 25 mg/kg, 10/50; females: 20/50, 13/60, 14/50, 10/50). The incidences of adenoma of the pituitary gland pars distalis in 25 mg/kg males and all groups of dosed females were below the NTP historical control range. The incidences of hyperplasia were not significantly different from those in the control groups. The incidences of mononuclear cell leukemia in 25 mg/kg males and females were significantly lower than those of the control groups (males: 33/50, 21/50, 26/50, 24/50; females: 20/50, 6/60, 13/50, 4/50). The incidence of mononuclear cell leukemia in females receiving 25 mg/kg was well below the NTP historical range. 2-YEAR STUDY IN MICE: Groups of 70 male and 70 female mice were administered 0, 1, 5, or 25 mg scopolamine hydrobromide trihydrate/kg body weight in distilled water by gavage for 104 to 105 weeks. Ten control animals and ten animals from each dose level were evaluated at 15 months. Survival, Body Weights, Clinical Findings, and Ophthalmic Examination Findings Survival of dosed males and females was similar to that of the controls. The mean body weights of males and females receiving 1 mg/kg were similar to those of the control groups throughout the majority of the study. The mean body weights of 5 mg/kg males and females were slightly lower than those of the controls. The mean body weights of males and females receiving 25 mg/kg were lower than those of the control groups after week 13. Clinical findings included bilateral pupillary dilation in all dosed male and female groups. Ophthalmic examination revealed no significant findings. Hematology: Hematocrit, hemoglobin concentration, and erythrocyte count in 25 mg/kg female mice were slightly lower than those in the control group. These results are consistent with development of a minimal normocytic, normochromic nonresponsive anemia. The anemia may be related to the lower body weights exhibited by these animals and are presumed to be due to a decreased nutritional status. Pathology Findings: The combined incidences of hepatocellular neoplasms (adenoma or carcinoma) occurred with a significant negative trend in males and females (males: vehicle control, 30/50; 1 mg/kg, 33/50; 5 mg/kg, 14/50; 25 mg/kg, 15/50; females: 22/51, 21/50, 16/50, 9/51). The combined incidences of hepatocellular neoplasms in 5 and 25 mg/kg males were within the NTP historical control range. The incidences of clear cell foci and eosinophilic foci in dosed male groups, and eosinophilic foci in 25 mg/kg females, were significantly lower than those of the control groups. The incidences of many spontaneously occurring nonneoplastic lesions were significantly lower in dosed mice than in the control groups and usually decreased with increasing dose. These included kidney nephropathy, alveolar epithelial hyperplasia, hyperplasia of the pancreatic islets, bone marrow myelofibrosis, hyperplasia of the pituitary gland pars distalis, cystic hyperplasia of the uterus, and hematopoietic cell proliferation of the spleen. The decreased incidences of these spontaneous lesions were most likely a result of lower body weights in dosed animals. GENETIC TOXICOLOGY: Scopolamine hydrobromide trihydrate did not induce mutations in any of five strains of Salmonella typhi murium, with or without S9 metabolic activation enzymes, nor did it induce sister chromatid exchanges in cultured Chinese hamster ovary cells, with or without S9. A weakly positive response was obtained, however, in a chromosomal aberrations test conducted in cultured Chinese hamster ovary cells with very high doses of scopolamine hydrobromide trihydrate in the presence of S9; without S9, no increase in aberrations was noted. Despite the evidence for chromosomal damage observed in vitro, no increase in the frequencies of micronucleated normochromatic erythrocytes was observed in peripheral blood samples of male or female mice exposed to scopolamine hydrobromide trihydrate for 14 weeks by gavage. CONCLUSIONS: Under the conditions of these 2-year gavage studies, there was no evidence of carcinogenic activity of scopolamine hydrobromide trihydrate in male or female F344/N rats or B6C3F1 mice administered 1, 5, or 25 mg/kg. Synonyms: Scopolamine hydrobromide, 6,7-epoxytropan-3-yl, euscopol, hydroscine hydrobromide, hyoscine bromide, (-)-hyoscine hydrobromide, hysco, isoscopil, scopolammonium bromide, (s)-tropate hydrobromide trihydrate, lα-tropyl-a-scopine

Journal Article↗
PubMed1989

Scopolamine and methylscopolamine differentially affect fixed-consecutive-number performance of male and female Wistar rats.

Male and female Wistar rats were trained on a fixed-consecutive-number schedule in which a response on a food lever was followed by the presentation of reinforcement when at least three, but not more than seven responses had been completed on a work lever. Subjects were treated with different doses of the centrally acting cholinergic antagonist scopolamine hydrobromide or the more peripherally active cholinergic antagonist scopolamine methylbromide (0.08, 0.16 or 0.32 mg/ml/kg) once behavior had stabilized. Scopolamine hydrobromide and scopolamine methylbromide dose-dependently decreased response rates in males and females. Scopolamine methylbromide decreased response rates more than equivalent doses of scopolamine hydrobromide and the rate-suppressant effects of both drugs were more marked in males than in females. Scopolamine hydrobromide dose-dependently decreased response accuracy, but differences between males and females were not observed. Response accuracy also decreased after scopolamine methylbromide, but did not vary as a function of the dose of the drug. The decrease in response accuracy induced by both drugs was attributable to an increase in the percentage of trials with a premature switch from the work lever to the food lever. Both scopolamine hydrobromide and scopolamine methylbromide dose-dependently increased the number of premature switches. Differences between males and females were not observed. Administration of scopolamine hydrobromide and scopolamine methylbromide also decreased the number of obtained reinforcers in a dose-dependent manner. Females obtained significantly fewer reinforcers than males, while scopolamine methylbromide affected the number of obtained reinforcers to a larger extent than scopolamine hydrobromide.

Animals↗
PubMed2001

Effect of supplementation of vitamin E and vitamin C on brain acetylcholinesterase activity and neurotransmitter levels in rats treated with scopolamine, an inducer of dementia.

In the present study, the effects of vitamins E and C on the levels of neurotransmitters and acetylcholinesterase activity in the brains of rats treated with scopolamine, an inducer of dementia, were examined. Fifty male Sprague-Dawley rats at the age of 5 wk were divided into five groups after 1 wk of adaptation and fed five different diets for 6 wk: a no-scopolamine group, which was a scopolamine-untreated group fed only a basal diet: a scopolamine-treated group fed a basal diet; a vitamin E-supplemented scopolamine-treated group: a vitamin C-supplemented scopolamine-treated group; and a vitamins E and C-supplemented scopolamine-treated group. Scopolamine was twice administered by intraperitoneal injection (300 mg/kg, body weight), 3 d and 20 min prior to sacrifice. Brain acetylcholinesterase activity was markedly reduced by scopolamine injection. However, the supplementation of vitamins E and C in the diet significantly increased the reduced brain acetylcholinesterase activity up to the level of the scopolamine-untreated group. Brain serotonin concentration in the vitamin C-supplemented scopolamine-treated group was significantly higher than that in the scopolamine-treated group. However, there were no significant differences in brain dopamine and norepinephrine concentrations among all groups. In conclusion, supplementation with vitamin E and/or vitamin C might be useful in maintaining brain acetylcholinesterase activity at the normal level and serotonin concentration for some extent under the condition to induce dementia by scopolamine administration.

Acetylcholinesterase↗
PubMed1992

The effect of estrogen treatment on scopolamine inhibition of lordosis.

Previous evidence indicates that the cholinergic muscarinic antagonist, scopolamine, inhibits lordosis in female rats. In the experiments reported here, the effects of various doses and repeated administrations of estrogen on the scopolamine inhibition of lordosis were examined. In the first experiment, intraperitoneal injections of scopolamine (1 mg/rat) completely inhibited lordosis in ovariectomized rats primed with low doses of estradiol benzoate (0.25 or 0.5 micrograms for 3 days) and progesterone (500 micrograms). However, scopolamine was significantly less effective in inhibiting lordosis in females primed with a higher dose of estradiol benzoate (25 micrograms for 3 days) and progesterone (500 micrograms). When hormone priming was repeated on subsequent weeks, scopolamine continued to inhibit lordosis in females that received 0.25 micrograms estradiol benzoate but was less effective in females primed with 0.5 micrograms. Scopolamine failed to inhibit lordosis in females treated with 25 micrograms estradiol benzoate on these later tests. In the second experiment, various doses of scopolamine (1, 2, or 4 mg/rat) were administered intraperitoneally to females primed with the highest dose of estradiol benzoate (25 micrograms) and progesterone (500 micrograms). Lordosis was inhibited equally by all scopolamine doses during the first week. As in the first experiment, scopolamine failed to inhibit lordosis at all doses on subsequent weeks of testing. These results indicate that the ability of scopolamine to inhibit lordosis is reduced by increasing the dose or the number of estrogen exposures. Because higher doses of scopolamine failed to restore its inhibitory effect on lordosis an upregulation of muscarinic receptors by estrogen cannot account for the reduced effectiveness of scopolamine.

Animals↗
PubMed1995

Influence of prefeeding and scopolamine upon performance in a delayed matching-to-position task.

The present study compared the influence of prefeeding (0, 10, 20 g or an unlimited amount of food pellets for a 90 min period prior to testing) with the effects of scopolamine (0, 0.03, 0.075 or 0.1 mg/kg s.c.) and scopolamine methylbromide (0.1 mg/kg s.c.) upon performance in the food reinforced delayed matching-to-position (DMTP) task. In preliminary studies using separate groups of rats, both scopolamine (but not scopolamine methylbromide) and prefeeding impaired choice accuracy in a seemingly delay-independent manner. Both treatments also increased omissions. However, while prefeeding increased all task latencies, scopolamine only increased sample latency. In a subsequent experiment, an intermediate dose of scopolamine (0.075 mg/kg s.c.) was directly compared with prefeeding in the same animals. Both treatments impaired choice accuracy, however, the effects of scopolamine were significantly larger than prefeeding. Conversely, prefeeding caused significantly greater omissions and larger increases in task latencies compared with scopolamine. These findings demonstrate some dissociation between the effects of scopolamine and prefeeding in the DMTP task, suggesting that the actions of scopolamine are not entirely due to reduction in motivation. Furthermore, the effects of scopolamine are likely to be centrally mediated.

Animals↗
PubMed1983

Psychomotor, physiological and cognitive effects of scopolamine and ephedrine in healthy man.

Three placebo-controlled double-blind studies in healthy volunteers were performed to reveal the psychophysiological effects of scopolamine, ephedrine and their combination. Single intravenous dose of scopolamine 6 micrograms/kg (scopolamine hydrobromide 7.4 micrograms/kg) impaired various psychomotor functions both subjectively and objectively. It caused sedation, impairment of coordinative and reactive skills, visual disturbances and impairment of shortterm memory. Oral scopolamine hydrobromide in single doses of 0.3 mg and 0.9 mg, or 0.9 mg b.d. for 3 days, had few effects. A slight impairment of shortterm memory and a decrease in the flicker fusion threshold were seen. The visual nearpoint and pupil diameter were increased and some subjects reported blurred vision and dizziness during treatment with scopolamine 0.9 mg b.d. Scopolamine showed clear cardiovascular effects in all studies: it decreased heart rate and systolic blood pressure. Ephedrine alone and in combination with scopolamine had no deleterious effects. On the contrary, it antagonized the scopolamine-induced impairment in the flicker fusion test and the decrease in blood pressure and heart rate. In sufficient doses scopolamine impairs various psychomotor and cognitive skills. An oral dose of scopolamine hydrobromide 0.9 mg on average has few effects, although they may be very striking in certain individuals. To avoid unwanted effects and diminution in performance by scopolamine, doses less than 0.9 mg should be used.

Blood Pressure↗
PubMed1986

Scopolamine effects on memory retention in mice: a model of dementia?

Scopolamine-treated normal young human subjects exhibit memory dysfunctions analogous to those observed in demented patients. The dysfunctions are reversible by physostigmine but not by d-amphetamine which suggests that the memory impairment is specifically related to reduced cholinergic transmission caused by scopolamine. Scopolamine-induced amnesia has been proposed as a model for dementia where reduced cholinergic function is the suspected cause. We report seven experiments in young adult mice which examine scopolamine's effects on memory retention and whether its amnestic effects are specifically blocked by cholinergic agonists or cholinomimetics. Young adult mice were trained to avoid footshock in a T maze and their retention tested 1 week after training. Pretraining subcutaneous injection of scopolamine improved retention scores of "undertrained" mice at a dose of 0.01 mg/kg but impaired at a dose of 0.1 mg/kg. Post-training injection showed no effect at 0.01 mg/kg, enhanced retention scores at 0.1 mg/kg, and impaired at 1.0 mg/kg. The impairment by 1.0 mg/kg was blocked by injection 45 min post-training of each of two cholinergic drugs but was also counteracted by six drugs which act upon five other neural systems (catecholamine, serotonin, glycine, GABA, and hormonal). When scopolamine was injected 40 min pretraining, and each of eight drugs was injected immediately after training, the amnestic effect of scopolamine was only partially counteracted. This suggests that scopolamine impaired acquisition, in addition to some impairment of memory processing. This was confirmed by a direct study of acquisition rates of the avoidance response; 0.1 mg/kg of scopolamine impaired acquisition. The overall results indicate that pretraining administration of scopolamine impairs learning and to some degree memory processing. Counteracting scopolamine-induced amnesia, by either pretraining or post-training drug administration, is not specific to the cholinergic system.

Animals↗
PubMed2000

Influence of grapefruit juice on scopolamine pharmacokinetics and pharmacodynamics in healthy male and female subjects.

OBJECTIVES: To investigate the effects of grapefruit juice on absolute bioavailability of scopolamine in healthy subjects and to evaluate differences in pharmacokinetics and pharmacodynamics between genders. SUBJECTS, MATERIAL AND METHODS: 14 healthy subjects (7 men and 7 women) received scopolamine 0.5 mg as intravenous infusion, and as oral ingestion with and without grapefruit juice on separate occasions. Serum and urine samples were analyzed using gas chromatography-ion trap tandem mass spectrometry. Changes in subjective state were determined up to 24 hours after drug administration. RESULTS: After oral administration, pretreatment with grapefruit juice led to a 30% increase in systemic bioavailability of scopolamine (p = 0.005) and a significant increase in time to reach peak serum concentration (tmax) of scopolamine (p < 0.001). The Cmax value (6.61+/-0.63 ng/ml) of scopolamine after i.v. administration in male subjects was significant higher compared with the value in female subjects (3.93+/-0.04 ng/ml; geometric mean +/- SEM; p = 0.007). No differences were found in urinary excretion rate of scopolamine and scopolamine glucuronide across genders and between the three different routes of scopolamine administration. Scopolamine produced time-dependent decrements in subjective alertness while contentment and calmness were not influenced. CONCLUSIONS: Pretreatment with grapefruit juice delayed the absorption and increased the bioavailability of scopolamine, whereas elimination was not significantly affected. This study identified an influence of gender on Cmax of scopolamine after i.v. infusion.

Adult↗
PubMed2006

Antidepressant efficacy of the antimuscarinic drug scopolamine: a randomized, placebo-controlled clinical trial.

CONTEXT: The need for improved therapeutic agents that more quickly and effectively treat depression is critical. In a pilot study we evaluated the role of the cholinergic system in cognitive symptoms of depression and unexpectedly observed rapid reductions in depression severity following the administration of the antimuscarinic drug scopolamine hydrobromide (4 microg/kg intravenously) compared with placebo (P = .002). Subsequently a clinical trial was designed to assess more specifically the antidepressant efficacy of scopolamine. OBJECTIVE: To evaluate scopolamine as a potential antidepressant agent. DESIGN: Two studies were conducted: a double-blind, placebo-controlled, dose-finding study followed by a double-blind, placebo-controlled, crossover clinical trial. SETTING: The National Institute of Mental Health. Patients Currently depressed outpatients aged 18 to 50 years meeting DSM-IV criteria for recurrent major depressive disorder or bipolar disorder. Of 39 eligible patients, 19 were randomized and 18 completed the trial. INTERVENTIONS: Multiple sessions including intravenous infusions of placebo or scopolamine hydrobromide (4 microg/kg). Individuals were randomized to a placebo/scopolamine or scopolamine/placebo sequence (series of 3 placebo sessions and series of 3 scopolamine sessions). Sessions occurred 3 to 5 days apart. MAIN OUTCOME MEASURES: Psychiatric evaluations using the Montgomery-Asberg Depression Rating Scale and the Hamilton Anxiety Rating Scale were performed to assess antidepressant and antianxiety responses to scopolamine. RESULTS: The placebo/scopolamine group showed no significant change during placebo infusion vs baseline; reductions in depression and anxiety rating scale scores (P<.001 for both) were observed after the administration of scopolamine compared with placebo. The scopolamine/placebo group also showed reductions in depression and anxiety rating scale scores (P<.001 for both) after the administration of scopolamine, relative to baseline, and these effects persisted as they received placebo. In both groups, improvement was significant at the first evaluation after scopolamine administration (P< or =.002). CONCLUSION: Rapid, robust antidepressant responses to the antimuscarinic scopolamine occurred in currently depressed patients who predominantly had poor prognoses.

Adult↗
PubMed1997

Locomotion and stereotypy induced by scopolamine: contributions of muscarinic receptors near the pedunculopontine tegmental nucleus.

In this study, we test whether blockade of muscarinic receptors near mesopontine cholinergic cell groups may contribute to locomotor activation induced by scopolamine. Unilateral or bilateral injections of scopolamine (10-150 micrograms) into the pedunculopontine tegmental nucleus (PPT) increased horizontal locomotion by 2-15 times in a dose-related way. Unilateral or bilateral injections of scopolamine into the PPT increased stereotypic behaviors (such as sniffing in one location or over large areas), self-biting and grooming. Carbachol (4 micrograms) injected into PPT reduced locomotion for 20 min, followed by 70 min of increased locomotion. When carbachol (4 micrograms) was injected into the PPT before scopolamine (3 mg/kg, i.p.), the activating effect of scopolamine was attenuated, but not when carbachol was injected after scopolamine. Therefore, carbachol appears to compete with scopolamine for muscarinic receptors near the PPT that mediate locomotor activating effects of systemic scopolamine. Haloperidol (0.1 mg/kg, i.p.) also attenuated the stereotypy and locomotion induced by scopolamine in the PPT. We hypothesize that scopolamine acts by blocking muscarinic receptors on mesopontine cholinergic neurons, thereby disinhibiting cholinergic neurons that can activate dopamine neurons.

Animals↗
PubMed1999

Effects of atropine and scopolamine on bradycardia and emetic symptoms in otoplasty.

OBJECTIVE: To assess the effects of unilateral or bilateral otoplasty on bradycardia and postoperative nausea and vomiting (PONV) and the efficiency of transdermal scopolamine in the prophylaxis of PONV. STUDY DESIGN: Post hoc assessment of the data from a double-blind, randomized study. METHODS: Fifty otoplasty patients were studied; half of them received randomly and in double-blind fashion a transdermal therapeutic system (patch) of scopolamine (TTS-scopolamine) as prophylaxis against PONV before general anesthesia. The placebo group received atropine 10 microg x kg(-1) intravenously during induction. RESULTS: The scopolamine-treated patients suffered more from moderate peroperative bradycardia (8/25; P < .05) than the atropine-treated patients (1/25). Two patients wearing a half of the TTS-scopolamine patch needed intravenous atropine. After unilateral otoplasty, none of the TTS-scopolamine-treated patients and 50% of the atropine-treated patients suffered from PONV. After bilateral operation, the respective incidences were 39% and 81% (P < .01). After unilateral otoplasty no patient needed droperidol, but after bilateral otoplasty, 12 of 19 of the atropine-treated and 4 of 18 (P < .05) of the scopolamine-treated patients needed droperidol. The mean numbers of doses of droperidol were 0.8+/-0.9 and 0.3+/-0.6 (P < .05), respectively. Two additional patients, wearing half of the TTS-scopolamine patch, suffered from mild central anticholinergic syndrome. CONCLUSION: TTS-scopolamine offers effective prophylaxis against PONV (auriculoemetic reflex), but does not protect from bradycardia (auriculocardiac reflex) in otoplasty. Cutting of the TTS-scopolamine patch may lead to undesirable side effects.

Anti-Arrhythmia Agents↗
PubMed2003

Effects of scopolamine on matching to sample paradigm and related tests in human subjects.

This was a double-blind placebo-controlled study with a cross-over design to examine the effects of scopolamine on cognitive functions in young healthy subjects. Scopolamine hydrobromide was administered subcutaneously to 12 subjects (mean +/- SD age 23.8 +/- 2.2 years) at doses of 0.3 and 0.6 mg in comparison with two placebo conditions. Scopolamine at both doses produced marked sedation as rated by subjects and an observer. In the continuous performance test, vigilance was impaired by both doses of scopolamine. The span of apprehension test showed differing results (only the high dose of scopolamine showed a performance decrement only in the three-character version of the span of apprehension test). Significant impairment by both doses of scopolamine was seen in immediate and delayed free recall, continuous visual recognition, running word recognition and running picture recognition. While scopolamine caused a significant slowing in average reaction times for simultaneous matching as well as for delayed matching, subjects made more errors under scopolamine compared to placebo only in delayed matching, not in simultaneous matching. Also, the main outcome of matching to sample showed significant effects only in delayed matching, not in simultaneous matching. Notable in this study is the incongruity between the simultaneous matching test and the span of apprehension test on the one hand and the other cognitive tests used on the other. These results demonstrated that scopolamine has a greater effect on memory than on attention. Thus, the scopolamine-induced effects in the present study seem to be more relevant to Alzheimer's disease in an advanced phase than to normal aging.

Adult↗
PubMedDate not supplied

Transdermally administered scopolamine vs. dimenhydrinate. I. Effect on nausea and vertigo in experimentally induced motion sickness.

The effect of transdermally administered scopolamine (TTS-scopolamine) (2.5 cm2 surface area, one and two patches) and dimenhydrinate (100 mg) on experimental motion sickness was examined in 16 healthy volunteers in a randomized double-blind study. Nausea was induced by Coriolis manoeuvre and vertigo by calorization of the ear. In all subjects, scopolamine was found in urine in concentrations indicating adequate absorption of the drug. One TTS-scopolamine, two TTS-scopolamine and dimenhydrinate caused a statistically significant reduction in nausea when compared with placebo. Dimenhydrinate was somewhat more effective against nausea than one TTS-scopolamine. Vertigo was significantly reduced after dimenhydrinate and two TTS-scopolamine. Side effects of both drugs were negligible, though gait disturbances and vertigo could occur occasionally after two TTS-scopolamine. No dose-response relationship was found between the urinary excretion of scopolamine and alleviation of nausea. Dimenhydrinate and TTS-scopolamine are both effective against motion sickness, the latter provided it is applied 6 to 8 hours before exposure to the stimulus causing the motion sickness.

Adult↗
PubMed2005

Scopolamine patch to prevent seasickness: clinical response vs. plasma concentration in sailors.

INTRODUCTION: Scopolamine is highly effective for the treatment of seasickness. Nevertheless, transdermal therapeutic system (TTS) scopolamine, despite high compliance on the part of persons treated by the drug, fails to provide protection against seasickness in 26-38% of patients. To the best of our knowledge, the correlation between scopolamine levels in plasma and its therapeutic effect under sailing conditions in the open sea is investigated for the first time in the present study. METHODS: Subjects were 61 crewmembers of naval vessels treated by TTS scopolamine. The therapeutic response at sea was documented by questionnaire. During a period ashore, a TTS scopolamine patch was applied in the same subjects. Blood samples were taken and an adverse effects questionnaire completed 8 h after scopolamine patch application. Scopolamine levels were determined using an established radio-receptor assay procedure. To verify the reproducibility of these measurements, blood samples were taken twice from most subjects, on separate days after different patch applications. Subjects were divided into "responders," who reported at least a moderate decrease in seasickness severity compared with their previous experience at sea without TTS scopolamine therapy, and "non-responders," who had only slight symptomatic relief or no relief at all. RESULTS: The mean scopolamine concentration in the plasma of the 37 responders (156.77 +/- 77.03 pg x ml(-1)) was significantly higher than the mean level in the 24 non-responders (97.03 +/- 73.34 pg x ml(-1); p = 0.005, simple t-test). CONCLUSIONS: Attempts to increase scopolamine levels in plasma by increasing the drug dosage or improving transdermal absorption should be considered for the treatment of "non-responders".

Absorption↗
PubMed1991

Nausea prophylaxis using transdermal scopolamine in the setting of patient-controlled analgesia.

We evaluated the effectiveness of transdermal scopolamine in patients receiving morphine via patient-controlled intravenous analgesia following intra-abdominal gynecologic surgery. Soon after arrival in the post-anesthesia recovery unit (time 0), patients were randomized either to receive or not receive a postauricular transdermal scopolamine patch. Nausea and vomiting were scored on a 0-3 scale at this time and at 2, 4, 6, and 24 hours. Patients were treated with droperidol as deemed necessary by the primary care nurse. Within 2-4 hours, transdermal scopolamine patients evidenced less nausea and vomiting and required less droperidol than their counterparts who did not receive transdermal scopolamine. A significant decline in the severity of nausea was noted in the transdermal scopolamine group between 2-24 hours; significant inter-group differences were noted for changes in nausea severity during the 0-6-hour and 0-24-hour intervals. Transdermal scopolamine patients evidenced a significant (P less than .05) decrease in the severity of vomiting during the first 2 hours, significantly different from the increase in the non-transdermal scopolamine patients. After the 4-hour assessment, no transdermal scopolamine patients required droperidol; nine doses were administered to the patients who were not given transdermal scopolamine (P less than .05). Thus, transdermal scopolamine therapy appears to be an effective means of treating the nausea and vomiting that are encountered after gynecologic surgery.

Administration, Cutaneous↗
PubMed1993

Time gradient for post-test vulnerability to scopolamine-induced amnesia following the initial acquisition session of a spatial reference memory task in mice.

The time course for vulnerability to the amnestic effects of the cholinergic antagonist, scopolamine, during the postacquisition period has been investigated. We have examined the effects of post-test injections of scopolamine (1 mg/kg ip) given at different times from 30 s for up to 6 h following the end of the first acquisition session of a concurrent spatial discrimination (reference memory) protocol in an 8-arm radial maze on subsequent long-term (24 h) retention performance in C57BL/6 mice. Results show that the immediate (30 s) post-test injection of scopolamine-HCl on Day 1 produces marked perturbation (amnesia) of long-term retention as attested to by significant deficits in various indices of spatial discrimination performance gain on Day 2 as compared to control subjects injected either with scopolamine-MBr or saline. The severity of this scopolamine-induced amnesia declines only slightly as a function of the treatment period 30 s-3 h post-test. However, no evidence for amnesia is observed if scopolamine-HCl injections are delayed for 6 h postsession. This important latter observation attests to the absence of any significant proactive effects of scopolamine on the ability of mice to perform the retention test via possible long-term effects on attention, motivation, or locomotor performance. These results thus constitute evidence for the existence of a limited (30 s-3 h) time gradient for vulnerability of the early memory trace to disruption by scopolamine. The present results are discussed in relation to our previous direct neurochemical observations describing the differential time courses of intervention of the ascending septohippocampal and nBM-cortical cholinergic pathways in the postlearning period. In particular, the presently observed time window concerning post-test vulnerability to scopolamine-induced amnesia corresponds more closely to the time course of the acute activation of the nBM-cortical cholinergic pathway, induced by testing with the same spatial memory protocol as used in the present study in mice.

Animals↗
PubMed1988

The effect of scopolamine and physostigmine on working and reference memory in pigeons.

A comparison of the effects of scopolamine and physostigmine on working memory and reference memory in White Carneaux pigeons was undertaken. In Experiment 1, the pigeons received injections of scopolamine hydrobromide (0.03 mg/kg), or saline. Scopolamine hydrobromide had greater disruptive effects on working memory trials than on reference memory trials, and the centrally active form of scopolamine disrupted working memory trial accuracy more than the peripherally active form. The differential sensitivity of accuracy on working memory trials to disruption by central cholinergic blockade was obtained even though the discrimination required on reference memory trials was more difficult. In Experiment 2, the pigeons received injections of scopolamine hydrobromide (0.015 mg/kg), physostigmine (0.075 mg/kg) both scopolamine and physostigmine, or saline. Physostigmine given with scopolamine was able to reverse the scopolamine-induced reduction of accuracy on working memory trials. In neither study did scopolamine promote accelerated forgetting as the delay interval was increased. These results indicate that manipulation of central cholinergic neurotransmitter systems influences working memory processes in the pigeon, but these effects occur without alterations in the ability of the birds to actively maintain information during the retention interval.

Animals↗
PubMed1983

Effects of scopolamine and methylscopolamine on classical conditioning of the rabbit nictitating membrane response.

Classical conditioning of the rabbit nictitating membrane response was accomplished by presenting tone- and light-conditioned stimuli for 800 msec before delivery of a 100-msec shock as the unconditioned stimulus. Scopolamine significantly retarded the rate of acquisition and final asymptotic performance of conditioned responses to the tone- and light-conditioned stimuli. Methylscopolamine was approximately 20 times less potent than scopolamine in retarding the rate of acquisition, and had no effect on the final asymptotic performance of conditioned responses. The retardation in acquisition of conditioned responses produced by scopolamine could still be detected 5 days after cessation of drug injections, indicating that the effects of scopolamine were on acquisition and not performance. In contrast, scopolamine and methylscopolamine had no affect on the development of long-term habituation produced by the unpaired presentations of tone, light and shock stimuli. Control experiments indicated that the acquisition of conditioned responses by animals injected with saline, scopolamine or methylscopolamine was not contaminated by the presence of changes in base-line responding, sensitization or pseudoconditioning. In addition, scopolamine and methylscopolamine did not affect the unconditioned nictitating membrane reflex. In previously trained animals, scopolamine produced a significant, approximately 25-db elevation in the intensity threshold of a tone-conditioned stimulus for elicitation of conditioned responses. It was concluded that scopolamine blocks the excitatory properties of tone stimuli and this accounts for its ability to retard the rate of acquisition of conditioned responses.

Acoustic Stimulation↗