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 307 records · Page 17Linked to original sources
PubMed1998

Scopolamine model of dementia: electroencephalogram findings and cognitive performance.

BACKGROUND: Memory and cognitive functions are known to decline with advancing age. Studies have suggested that this may be due to a decrease in cholinergic function in the brains of elderly people. This review aims to assess studies documented in the literature dealing with the 'scopolamine model' of dementia. METHODS: Sources included MedLine searches from the last 10 years (search for 'scopolamine model', 'dementia', 'electroencephalogram', 'cognition') and references from original and review articles. The aim was to include human and animal studies occupying the cholinergic hypothesis in cognitive dysfunction. Electroencephalographic (EEG) and cognition findings were considered. RESULTS: Scopolamine influences delta, theta, alpha and beta activity in EEG and partially mimics the EEG changes found in patients with senile dementia or dementia of the Alzheimer type. Effects on different cognitive functions have been extensively documented. CONCLUSION: Scopolamine produces similar memory deficits seen in the elderly, but the drug cannot induce the full range of deficits seen in patients with Alzheimer's disease. Various aspects of memory were unaffected by scopolamine administration. Memory improvements in elderly subjects can be achieved after cholinergic stimulation.

Aged↗
PubMed1992

Monoclonal antibody-based enzyme immunoassay for the quantitative determination of the tropane alkaloid, scopolamine.

A monoclonal antibody (SP1-4-A2) against scopolamine was produced, characterized, and used to develop a sensitive and selective, competitive enzyme immunoassay for the quantitation of the alkaloid. The assay uses nor-scopolamine-N-beta-propionic acid coupled to alkaline phosphatase as tracer and is linear from 10 pg to 10 ng of scopolamine. As little as 10 pg of scopolamine can be quantitated in an unprocessed plant extract or in human serum after suitable dilution, corresponding to detection limits of 0.1 ng scopolamine/ml of plant extract or 0.5 ng/ml of serum. The assay is more selective for scopolamine (percent cross-reactions for hyoscyamine = 0.21%, 6-hydroxy-hyoscyamine = 0.17%) than previously reported immunoassays. The assay format was designed to minimize intra- and inter-plate variabilities which are, on an average, all below 3% (coefficients of variation). The assay reported here has been validated against an HPLC-based technique using plant samples and was shown to correlate closely (y = 0.959 x + 0.14, r = 0.982).

Antibodies, Monoclonal↗
PubMed1984

[Prevention of motion sickness with a transdermal therapeutic system containing scopolamine. A randomized, comparative double-blind study in the German Federal Navy].

To test the prophylactic value of anti-motion sickness drugs, a randomized double-blind trial was undertaken on 46 young, healthy, male volunteer marines. Comparison was made between a transdermal therapeutic system (TTS) containing as the effective agent scopolamine (TTS-scopolamine) and proprietary meclozine tablets. An artificial "sea voyage" served to produce motion sickness, each subject sitting by himself on an artificially tilting "island", on two days for 30 minutes. Without treatment, 19 of the 46 subjects developed symptoms of motion sickness requiring treatment. After administration of TTS-scopolamine or meclozine tablets (double-dummy technique) the motion sickness score was reduced by 89% and 59%, respectively. There was a reduction on the visual analog scale of 98% and 59%, respectively. Probability of error (Fisher's exact probability test) for assuming therapeutic advantage of TTS-scopolamine over meclozine tablets was 13.5%. A pre-set significance level of 5% was thus not reached. This trial shows that TTS-scopolamine, even in a brief exposure, has at least the same effectiveness as meclozine, in addition to avoiding the gastrointestinal tract and maintaining with certainty a constant blood level over three days.

Administration, Topical↗
PubMed1978

Selective blockade by scopolamine of synaptic responses in cat's caudate nucleus and its modification by lesions of the substantia nigra.

Because it is commonly believed that acetylcholine is a synaptic transmitter in the caudate nucleus and that the reduction of striatal biogenic amines in Parkinson's disease leads to acetylcholine supersensitivity in the caudate nucleus, we investigated the effects of the muscarinic blocking agent scopolamine on synaptic responses of neurons in the intact feline caudate nucleus and in the caudate nucleus depleted of dopamine by long-standing nigrostriatal lesions. In the intact caudate nucleus, micro-iontophoretic application of scopolamine selectively blocked the neuronal responses to stimulation of the caudate nucleus near the recording site without affecting the responses to stimulation of the sensorimotor cortex or the substantia nigra in the same fashion. This suggests that acetylcholine is a synaptic transmitter of caudate interneurons. Responses to thalamic stimuli were also blocked by scopolamine, suggesting that acetylcholine may be a transmitter of thalamic afferents although the course of these afferents is unclear. In the dopamine-depleted caudate nucleus scopolamine was more effective than in the intact caudate nucleus blocking the neuronal responses to stimulation of the caudate nucleus. This greater blocking effect by scopolamine suggests an increased effect of endogenous acetylcholine in this response and supports previous observations of an increased excitatory effect of iontophoretic acetylcholine in the dopamine-depleted caudate nucleus. These results suggest that the acetylcholine supersensitivity which follows nigrostriatal degeneration may be due to increased effectiveness of synaptic transmission by cholinergic interneurons in the caudate nucleus.

Acetylcholine↗
PubMed1993

Scopolamine affects short-term memory but not inferior temporal neurons.

Effects of scopolamine on performance of a delayed matching-to-sample task and on the properties of neurons in anterior-ventral inferior temporal (IT) cortex were examined in two monkeys. Both monkeys were impaired on the task after systemic administration of scopolamine, suggesting that scopolamine disrupts recency memory. Despite the behavioral deficit, neurons in IT cortex, a region having an important role in visual memory and neuronal properties consistent with that role, were largely unaffected by scopolamine. This dissociation between the behavioral and neuronal effects of scopolamine indicates that the drug either acts at a different site or disrupts unobserved mechanisms at the IT site.

Algorithms↗
PubMed2001

Endomorphin-1 improves scopolamine-induced impairment of short-term memory via mu1-opioid receptor in mice.

The effects of intracerebroventricular injection of endomorphin-1 and 2, endogenous mu-opioid receptor agonists, on the scopolamine-induced impairment of spontaneous alternation performance associated with short-term memory were investigated in mice. Endomorphin-1 (0.03 microg) inhibited scopolamine (1 mg/kg)-induced impairment of spontaneous alternation performance without affecting total arm entries, while endomorphin-2 (0.01-10 microg) failed to significantly influence the scopolamine (1 mg/kg)-induced impairment. Endomorphin-1 (0.03 microg) itself had no marked effects on spontaneous alternation performance in intact mice. Although beta-funaltrexamine (5 microg), a mu-opioid receptor antagonist, did not significantly affect the inhibitory effects of endomorphin-1 (0.03 microg) on the scopolamine (1 mg/kg)-induced impairment, naloxonazine (35 mg/kg), a mu1-opioid receptor antagonist, significantly reversed the inhibitory effects of endomorphin-1 (0.03 microg) on the impairment. Naloxonazine (35 mg/kg) unlike beta-funaltrexamine (5 microg) did not significantly influence the scopolamine (1 mg/kg)-induced impairment of spontaneous alternation performance. These results suggest that endomorphin-1 improves the disturbance of short-term memory resulting from cholinergic dysfunction through the mediation of mu1-opioid receptors.

Analgesics, Opioid↗
PubMed1995

Effects of the cholinomimetic SDZ ENS-163 on scopolamine-induced cognitive impairment in humans.

Scopolamine-induced cognitive impairment was used in healthy men to evaluate the central nervous system activity of the new cholinomimetic SDZ ENS-163. Eighteen subjects were treated in a crossover design with oral placebo/intravenous saline, 50 mg of oral SDZ ENS-163/intravenous saline, oral placebo/0.4 mg of intravenous scopolamine, and 50 mg of oral SDZ ENS-163/0.4 mg of intravenous scopolamine. The administration of placebo with scopolamine caused significant cognitive impairment, as assessed by the Computerized Neuropsychological Test Battery (CNTB), and also decreased salivation and heart rate. In contrast, SDZ ENS-163 with saline had no effect on CNTB scores, increased salivation, and increased heart rate. Despite the observed cholinomimetic effects of SDZ ENS-163 when administered with saline, the changes in CNTB scores, heart rate, and salivation were indistinguishable between placebo/scopolamine and SDZ ENS-163/scopolamine. Thus, 50 mg of oral SDZ ENS-163 has cholinomimetic activity in normal men, but this dose is insufficient to reverse the muscarinic effects of 0.4 mg of intravenous scopolamine.

Adult↗
PubMed2000

Effects of the cannabinoid ligand SR 141716A alone or in combination with delta9-tetrahydrocannabinol or scopolamine on learning in squirrel monkeys.

To investigate the effects of the cannabinoids on learning and on scopolamine-induced disruptions in learning, delta9-tetrahydrocannabinol (delta9-THC), SR 141716A (an antagonist at CB1 receptors) and scopolamine were administered to squirrel monkeys responding in a repeated-acquisition task. In this task, monkeys acquired a different three-response sequence each session and responding was maintained by food presentation under a second-order fixed-ratio 5 schedule. When either delta9-THC (0.1-0.56 mg/kg, i.m.) or SR 141716A (1-10 mg/kg, i.m.) was administered alone, 60 and 75 min before the session, respectively, both cannabinoid ligands dose-dependently decreased the overall rate of responding and increased the overall percentage of errors. However, at a dose that had little or no effect alone (i.e. 1 mg/kg), SR 141716A antagonized the disruptive effects of delta9-THC (0.18-1.8 mg/kg) on acquisition, shifting the dose-effect curves for rate of responding and percentage of errors at least 1/2 log unit to the right. Finally, when either delta9-THC (0.001-1 mg/kg) or SR 141716A (0.32-10 mg/kg) was administered with scopolamine (0.01 or 0.032 mg/kg, 15 min before the session), greater rate-decreasing and error-increasing effects were obtained than with scopolamine alone. These results suggest that while low doses of SR 141716A can antagonize the effects of delta9-THC in squirrel monkeys, high doses can also disrupt acquisition when administered alone and potentiate the disruptive effects of scopolamine on acquisition.

Animals↗
PubMedDate not supplied

Scopolamine enhances generalization between odor representations in rat olfactory cortex.

Acetylcholine (ACh) has a critical, modulatory role in plasticity in many sensory systems. In the rat olfactory system, both behavioral and physiological data indicate that ACh may be required for normal odor memory and synaptic plasticity. Based on these data, neural network models have hypothesized that ACh muscarinic receptors reduce interference between learned cortical representations of odors within the piriform cortex. In this study, odor receptive fields of rat anterior piriform cortex (aPCX) single-units for alkane odors were mapped before and after either a systemic injection of the muscarinic receptor antagonist scopolamine (0.5 mg/kg) or aPCX surface application of 500 microM scopolamine (or saline/ACSF controls). Cross-habituation between alkanes differing by two to four carbons was then examined following a 50-sec habituating stimulus. The results demonstrate that neither aPCX spontaneous activity nor odor-evoked activity (receptive field) was affected by scopolamine, but that cross-habituation in aPCX neurons was enhanced significantly by either systemic or cortical scopolamine. These results indicate that scopolamine selectively enhances generalization between odor representations in aPCX in a simple memory task. Given that ACh primarily affects intracortical association fibers in the aPCX, the results support a role for the association system in odor memory and discrimination and indicate an important ACh modulatory control over this basic sensory process.

Animals↗
PubMed1993

Nefiracetam (DM-9384) preserves hippocampal neural cell adhesion molecule-mediated memory consolidation processes during scopolamine disruption of passive avoidance training in the rat.

Scopolamine (0.15 mg/kg), a muscarinic antagonist, when administered during training or at a discrete 6-h posttraining time point, is demonstrated to inhibit the recall of a step-down passive avoidance response when tested at 24 and 48 h after task acquisition. Nefiracetam (3 mg/kg), a piracetam-related nootropic, when given with scopolamine during training tended to improve task recall, and this effect was more pronounced when given at the 6-h posttraining time. Co-administration of nefiracetam with scopolamine was not necessary to achieve the antiamnesic action, as nefiracetam given during training significantly improved the memory deficits produced by scopolamine at the 6-h posttraining time. The paradigm-specific increase in hippocampal neural cell adhesion molecule sialylation, which is observed during consolidation of a passive avoidance response, was attenuated by the presence of scopolamine during training and at the 6-h posttraining time, and this effect was reversed by co-administration of nefiracetam, albeit in a paradigm-independent manner. These results suggest nefiracetam exerts a neurotrophic action that protects memory consolidation from drug interventive insults.

Animals↗
PubMed1990

Potential of moclobemide to improve cerebral insufficiency identified using a scopolamine model of aging and dementia.

After a baseline performance assessment, 28 healthy male volunteers received subcutaneous injections of scopolamine hydrobromide to induce deficits in memory, attention and cognitive processes. Subsequent performance testing established the decrements caused by the scopolamine, and then each subject was given one of 3 investigational drugs including moclobemide, or placebo, according to a latin-square design. Parallel versions of the test procedures were used to assess drug effects on the scopolamine-induced cognitive deficits. Whereas marked and statistically significant impairment was identified 60 min after scopolamine injection, the global analysis revealed statistically significant superiority of moclobemide over placebo at 120 min in relieving the scopolamine-induced decrement in performance. These results show that moclobemide may improve cognition in conditions associated with cholinergic deficit. It may therefore be especially indicated in the treatment of cognitive decline occurring with normal aging, depression in elderly people and Alzheimer's disease.

Adult↗
PubMed1989

Effects of scopolamine on verbal memory; a retrieval or acquisition deficit?

This study examines the relationship between encoding and retrieval factors in producing the well-documented scopolamine-induced deficits in verbal memory. Subjects were required to learn word lists of 10 items, and were given a total of 8 acquisition trials per list. While the placebo group achieved criterion within 4 acquisition trials, the group treated with scopolamine failed to reach criterion at all, with recall levelling off within 4 acquisition trials. Acquisition curves for subjects treated with scopolamine paralleled those obtained for the placebo group. Performance on delayed recall and recognition tests indicated that the subjects had in fact successfully encoded items in long-term memory, but had been unable to retrieve them in free recall. The results suggest a retrieval problem in what has traditionally been considered a scopolamine-induced encoding deficit. We suggest that scopolamine may disrupt the organization of material at input, so that items which have achieved durable storage are not accessible for free recall.

Adolescent↗
PubMed2006

Acteoside of Callicarpa dichotoma attenuates scopolamine-induced memory impairments.

We previously reported that ten phenylethanoid glycosides including acteoside isolated from the leaves and twigs of Callicarpa dichotoma significantly attenuated glutamate-induced neurotoxicity. In the present study, we examined anti-amnesic activity of acteoside using scopolamine-induced (1 mg/kg body weight, s.c.) amnesic mice with both passive avoidance and Morris water maze tests. Acute oral treatment (single administration prior to scopolamine treatment) of mice with acteoside (1.0, 2.5 mg/kg body weight) significantly mitigated scopolamine-induced memory deficits in the passive avoidance test. It is interesting to note that prolonged oral daily treatment of mice with much lower amount (0.1 mg/kg body weight) of acteoside for 10 d reversed the scopolamine-induced memory deficits. In the Morris water maze, prolonged oral treatment with acteoside (prolonged daily administration of 1.0 mg/kg body weight for 10 d) significantly ameliorated scopolamine-induced memory deficits showing the formation of long-term and/or short-term spatial memory. We suggest, therefore, that acteoside has anti-amnesic activity that may ultimately hold significant therapeutic value in alleviating certain memory impairment observed in Alzheimer's disease.

Animals↗
PubMed1990

WEB 1881 FU ameliorates impairment of working memory induced by scopolamine and cerebral ischemia in the three-panel runway task.

Using a repeated acquisition procedure in a 3-panel runway apparatus, the effect of WEB 1881 FU on impairment of working memory produced either by scopolamine or by cerebral ischemia was investigated in rats and compared with those of aniracetam and Ca hopantenate. Intraperitoneal injection of scopolamine at 0.56 mg/kg significantly increased the number of errors (pushes made on the two incorrect panels of the three panel-gates located at each choice point). WEB 1881 FU at 10-32 mg/kg, p.o., caused a dose-related reduction in the increase of errors expected in the scopolamine-treated rats. Aniracetam at 10-100 mg/kg, p.o., or Ca hopantenate at 100 and 560 mg/kg, p.o., also significantly diminished the increase in errors induced by 0.56 mg/kg of scopolamine. Cerebral ischemia for 5 min significantly increased errors in the 3-panel runway task. WEB 1881 FU at 32 and 56 mg/kg, administered p.o. immediately after blood flow recirculation and again 1 hr before the runway test, conducted 24 hr after ischemia, significantly reduced the increase in errors expected to occur after 5 min of ischemia. Aniracetam at 32 and 100 mg/kg, p.o., similarly diminished the increase in errors in ischemic rats. These findings suggest that WEB 1881 FU has a beneficial effect on memory that has been impaired by scopolamine or by cerebral ischemia.

Animals↗
PubMed2004

The effects on place cells of local scopolamine dialysis are mimicked by a mixture of two specific muscarinic antagonists.

Using a dialysis probe near CA1 hippocampal recording electrodes, we infused nonspecific (scopolamine) and specific (methoctramine, pirenzepine) antagonists of muscarinic cholinergic transmission to determine their effects on the positional firing properties of place cells. Both low (0.5 mM) and high (2.0 or 3.0 mM) scopolamine significantly decreased in-field firing rate, increased the ratio of out-of-field to in-field rate, and reduced the smoothness of rate maps, while tending to increase out-of-field rate. Thus, local nonspecific muscarinic blockade mimicked the effects seen with intracerebroventricular application, suggesting that blockade of receptors local to the recorded cells plays an essential role. Unexpectedly, dialysis of scopolamine reduced locomotor activity, again duplicating the effects of intracerebroventricular administration. Most effects of methoctramine (1.0 mM), which blocks presynaptic m2 and m4 receptors, were initially strong but then diminished over hours. Methoctramine produced a significant increase only in out/in ratio and out-of-field rate, whereas it tended to increase in-field rate and monotonically decrease smoothness. Pirenzepine (3.0 mM), which blocks postsynaptic m1 receptors, produced a significant increase only in out/in ratio, whereas it tended to increase out-of-field rate and decrease in-field rate; all these effects were monotonic with respect to time. A mixture of methoctramine plus pirenzepine recapitulated the place-cell effects of scopolamine, although neither the mixture nor its separate components affected behavior. We conclude that the effects of scopolamine on place cells likely result from a combination of blockade of postsynaptic m1 receptors, leading to reduced excitability, with blockade of presynaptic m2 and m4 receptors, leading to increased out-of-field firing.

Action Potentials↗
PubMed1987

Relative effects of scopolamine and electroconvulsive shock upon habit reversal in white rats.

30 adult male white rats were equally divided into control, scopolamine, and electroconvulsive shock groups to learn 20 successive reversal problems in an E-maze for water after 23 1/2 hr. of deprivation. The noncorrection method was used. After 1 mo. of preliminary training, each scopolamine animal received an intraperitoneal injection of 1 mgm of scopolamine hydrobromide per kgm of body weight while each in the shock group was given an ECS of 35 mA for .2 sec. at the end of every 10 daily trials. When a rat obtained 9 correct of 10 trials, the goal was switched to the opposite side of the maze. Controls were much superior to both experimental groups. While scopolamine animals experienced more detrimental effects initially, they caught up with the shock group and finally became superior. This shift is interpreted in terms of building tolerance to scopolamine and increasing anxiety to shock as effects of differential treatments accumulated.

Animals↗
PubMed1984

A reduction of vestibulo-visual integration during transdermally administered scopolamine and dimenhydrinate. A presentation of gain control theory in motion sickness.

The effect of transdermally administered scopolamine (TTS scopolamine) (release rate 5 micrograms/h) and dimenhydrinate (100 mg) was examined on optovestibular nystagmus in 16 volunteers in a randomized double-blind trial. A statistically significant decrease in the optokinetic part of nystagmus was observed during all treatments. Most profound reduction was found during treatment with two TTS scopolamine. The vestibular part was reduced by treatment with two TTS scopolamine, only. The results indicate that scopolamine and dimenhydrinate exert their effect in motion sickness by reducing the vestibular and visual influx and by partly inhibiting the integrative functioning of the vestibular nuclei. In their action, the motion sickness drugs seem to assist the cerebellum by diminishing impulses from various orientation reflexes in order to preserve the functional capacity of the central nervous system. Different symptoms in motion sickness seem to arise when the vestibular gain operates beyond the normal range of the cerebellar control mechanisms.

Dimenhydrinate↗
PubMed1991

Metabolism in vivo of the tropane alkaloid, scopolamine, in several mammalian species.

1. In vivo metabolism of scopolamine was studied in rats, mice, guinea pigs and rabbits. The structures of eight urinary metabolites including unchanged drug were elucidated by mass and nuclear magnetic resonance spectrometry. Determination of these metabolites was achieved by a g.l.c. method using a semi-capillary column. 2. The major metabolites in rats were the three phenolic metabolites, p-hydroxy-, m-hydroxy- and p-hydroxy-m-methoxy-scopolamine. 3. Significant intra-species difference of the metabolism was observed in rabbits. Tropic acid was the major metabolite in two rabbits out of three, while the other rabbit excreted mainly unchanged scopolamine, accompanied by five metabolites. Tropic acid was also the major metabolite in guinea pigs, but was of minor importance in mice. 4. The dehydrated metabolites, aposcopolamine and aponorscopolamine, were abundantly excreted in guinea pigs, moderately in mice, and least in rabbits and rats. 5. Excretion of glucuronide conjugates of scopolamine and norscopolamine were high in mice compared with other species. On the other hand, phenolic metabolites in rat urine; and tropic acid in rabbit and guinea pig urine, were excreted as the free forms. 6. These results indicate that scopolamine metabolism is highly species-specific.

Animals↗