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PubMed1991

[Scopolamine poisoning as a cause of acute paranoid hallucinatory psychoses].

In 1988 two patients intoxicated with scopolamine were treated in the department of psychiatry. Clinically an acute paranoid-hallucinatory psychosis was to be observed. Similar cases were reported from other parts of the country, partly proved by toxicological findings. In the cases seen by us scopolamine was applicated secretly in drinks and food with criminal intention. Diagnostic, therapeutic and historical aspects of intoxication with scopolamine are discussed.

Adult↗

PubMed1991

Effect of L-alpha-glyceryl-phosphorylcholine on amnesia caused by scopolamine.

The present study was carried out to test the effects of L-alpha-glycerylphosphorylcholine (L-alpha-GFC) on memory impairment induced by scopolamine in man. Thirty-two healthy young volunteers were randomly allocated to four different groups. They were given a ten day pretreatment with either L-alpha-GFC or placebo, p.o., and on the eleventh day either scopolamine or placebo, i.m. Before and 0.5, 1, 2, 3, and 6 h after injection the subjects were given attention and mnemonic tests. The findings of this study indicate that the drug is able to antagonize impairment of attention and memory induced by scopolamine.

Adult↗

PubMed1990

[Effects of scopolamine and diazepam on delayed discrimination behavior in rats].

The effects of subcutaneously administered scopolamine and diazepam on simultaneous as well as delayed light-dark discrimination behavior were studied in a Y-maze situation using rats. In simultaneous discrimination behavior, running responses to the lighted side of either the right or left arm of the Y-maze were regarded as correct choices. In delayed discrimination behavior, running responses to the lighted side at several delay times (0. 2, 4, and 8 sec) after extinguishment of the light were regarded as correct choices. In the saline test, the percentage of correct choices decreased as the delay time was extended. Scopolamine at 0.03 mg/kg decreased the percentage of correct choices as the delay time was extended within the range of 0 sec through 4 sec. Diazepam both at 1 mg/kg and at 2 mg/kg decreased the percentage at the delay times of 0, 2, and 4 sec but this decreasing effect was not dependent on the delay time. The same doses of these drugs had no effect on simultaneous discrimination behavior. These results suggest that scopolamine at 0.03 mg/kg and diazepam both at 1 mg/kg and at 2 mg/kg disrupt delayed discrimination behavior in different ways.

Animals↗

PubMed1988

Comparison of the effects of bifemelane hydrochloride and indeloxazine hydrochloride on scopolamine hydrobromide-induced impairment in radial maze performance.

The antiamnesic effects of bifemelane hydrochloride (bifemelane) and indeloxazine hydrochloride (indeloxazine) on radial maze performance in rats were assessed. This performance was dependent on working memory and spatial memory, without aversive electric stimuli. When administered alone, neither bifemelane nor indeloxazine had an effect on the task performance of normal rats. However, impairment of the performance of rats induced by scopolamine hydrobromide (scopolamine) injection was dose-dependently reduced by oral treatment with bifemelane. On the other hand, indeloxazine, which was reported to enhance the learning behavior in a passive avoidance test, did not improve the radial maze task performance of scopolamine-treated rats. It has been shown that dysfunction of the cholinergic neuronal system plays an important role in memory loss and that bifemelane induces recovery of reduced cerebral cholinergic neuronal activity associated with brain ischemia or aging. In accordance with these previous findings, our results suggest that bifemelane is useful in the treatment of memory loss and cognitive dysfunction in patients with dementia and cerebrovascular disease.

Animals↗

PubMedDate not supplied

Effects of oxiracetam-scopolamine combinations on shuttle-box avoidance acquisition in mice.

The nootropic drug oxiracetam and the anticholinergic agent scopolamine were tested, alone or in combination, on shuttle-box avoidance acquisition and locomotor activity in mice of the CD-1 strain. Both drugs, given separately, slightly but significantly enhanced avoidance performance, but only scopolamine increased locomotor activity. Combinations of the 2 drugs, in some instances, enhanced avoidance performance more than drugs given separately, but the disinhibitory property of scopolamine makes it difficult to understand the role played by cholinergic mechanisms in these effects.

Animals↗

PubMed1986

Accidental mydriasis from scopolamine patches.

Although scopolamine is rarely intentionally applied directly to the eye, accidental contamination can occur after touching or handling a transdermal scopolamine patch, worn behind the ear to prevent motion sickness, and then rubbing one's eyes or handling contact lenses. An acute episode of prolonged cycloplegia with no admission of use of any medication by the patient was only resolved after direct questioning as to the use of a scopolamine patch revealed its removal within a 36 hour period.

Administration, Topical↗

PubMed1987

Efficacy of transdermal scopolamine against seasickness: a 3-day study at sea.

Transdermal scopolamine has been reported to provide protection against motion sickness, both while sailing at sea (7-8 h) and under experimental conditions. In this study, we tested the efficacy of transdermal scopolamine and evaluated its side effects during a 72-h cruise at sea. We tested 38 male volunteers, 20-25 years old, who were located on a 3000-ton vessel. The presence of seasickness, defined by Graybiel's diagnostic criteria, was used to calculate percent protection. When sickness was considered as malaise II or more, the drug provided 74, 73, and 39% protection during the three sailing days, respectively. There were no significant differences in the magnitude of the side effects reported by experimental and placebo groups. We conclude that transdermal scopolamine's efficacy against seasickness during a 3-day cruise was not associated with significant side effects and, therefore, we find the drug suitable for long-term use by sailing crews.

Administration, Cutaneous↗

PubMed1985

Pharmacological restoration of scopolamine-impaired memory.

In training for passive avoidance using a device of the step-down type, the nootropic agents piracetam (60 mg/kg orally) and centrophenoxine (100 mg/kg, i. p.) do not facilitate learning, while the ergot alkaloid elymoclavine (1 mg/kg, i. p.) tends to have a positive effect on learning and memory. The muscarine cholinergic receptor blocker scopolamine (2 mg/kg, i. p.) substantially deteriorates short-term memory in passive avoidance training. Piracetam in a dose of 600 mg/kg does not change the negative effect of scopolamine on the memory, while centrophenoxine (100 mg/kg) and elymoclavine (1 mg/kg) eliminate it in view of the fact that the impairment of the short-term memory in the reported experiments was induced by the cholinolytic agent scopolamine, it should be assumed that the observed effects of piracetam, centrophenoxine and elymoclavine are due to definite interactions between the cerebral cholinergic and monoaminergic mechanisms.

Animals↗

PubMed1985

Transderm scopolamine efficacy related to time of application prior to the onset of motion.

We evaluated Transdermal Scopolamine related to the time of application prior to the onset of motion. In this study 44 subjects participated. The first group applied the transdermal disc within 4 h and the second group 8 h or more prior to the onset of motion. We observed a significant decrease in the incidence and the degree of motion sickness for the group with at least 8 h of scopolamine application prior to sea travel. Therefore, the transdermal scopolamine system should be applied at least 8 h before potentially disturbing motion to provide adequate prophylaxis against motion sickness. We found no significant difference in motion sickness susceptibility between men and women, in contrast to earlier reports.

Administration, Topical↗

PubMed1984

Drug treatment of motion sickness: scopolamine alone and combined with ephedrine in real and simulated situations.

In two placebo-controlled, double-blind, randomized trials scopolamine (0.3 mg) alone or combined with ephedrine (25 mg) was tested for its effectiveness in the prevention of seasickness during 24 h at sea and of motion sickness in rotating chair tests in a laboratory. Scopolamine was effective both alone and in combination with ephedrine, which supports the hypothesis on central cholinergic overactivity in the pathogenesis of motion sickness. Ephedrine did not markedly increase the effectiveness of scopolamine. Side-effects were slight and did not disturb the operating ability of the volunteers.

Adult↗

PubMed1984

A homeostatic model of Pavlovian conditioning: tolerance to scopolamine-induced adipsia.

Several experiments support a model proposing that tolerance to scopolamine-induced adipsia involves an interplay between processes of homeostatic regulation and Pavlovian conditioning. In Experiment 1a, rats given access to water while under the influence of scopolamine developed adipsic tolerance, whereas rats denied access to water in the drug state did not. In Experiment 1b, rats displayed adipsic tolerance only when scopolamine was administered with cues associated with previous drug injections. In Experiment 1c, adipsic-tolerant rats showed a polydipsic response to an injection of phenobarbital (which unconditionally augments water consumption) relative to nontolerant animals with the same pharmacological history. Experiment 2 assessed the effect of deprivation level on the Pavlovian extinction of adipsic tolerance. Rats satiated with water during extinction showed a loss of adipsic tolerance, whereas water-deprived rats did not. The present model is discussed in relation to (a) tolerance in other response systems such as morphine analgesia, (b) theories of extinction for nonpharmacological Pavlovian conditioning, and (c) homeostatic regulation and incentive motivation.

Animals↗

PubMed1981

Experimental motion sickness: efficacy of transdermal scopolamine plus ephedrine.

A double-blind, placebo-controlled study compared the efficacy of transdermal therapeutic system-scopolamine administered alone and combined with ephedrine sulfate given orally in doses of 12.5, 25, and 50 mg. Eight normal male students were exposed to stressful accelerations in a slow-rotation room after receiving 10 apparently identical treatments comprising the four drugs and six placebos. Efficacy of the drug was defined in terms of the placebo range and categorized as beneficial, inconsequential, or detrimental. None of the effects was detrimental. Overall beneficial effects were 60% for transdermal therapeutic system-scopolamine (plus placebo) and 57% for the three transdermal therapeutic system-scopolamine plus ephedrine combinations.

Adult↗

PubMed1978

High pressure liquid chromatographic determination of atropine sulfate and scopolamine hydrobromide in tablets.

A reverse phase high pressure liquid chromatographic (HPLC) system utilizing ion-pairing, similar to that previously reported for methscopolamine bromide, was developed for the quantitation of atropine sulfate and scopolamine hydrobromide in tablets. This HPLC system is capable of differentiating the major tropane alkaloids, with the exception of the atropine-hyoscyamine optical isomer pair, by their k' values and separating a significant degradation product, tropic acid. Optimum sensitivity is obtained by using a variable wavelength ultraviolet detector at 230 nm resulting in a detection limit of less than 0.5 microgram alkaloid/injection. The response is linear in the range of 3--19 microgram atropine sulfate and scopolamine hydrobromide. The coefficient of variation for injection reproducibility in less than 1%. The method has been applied to composite and individual tablet assays of scopolamine hydrobromide and atropine sulfate. The HPLC results are comparable (within 1%) to those obtained using the USP procedure; the HPLC method requires less sample preparation.

Atropine↗

PubMed1993

Intraseptal galanin potentiates scopolamine impairment of delayed nonmatching to sample.

Galanin coexists with ACh in the basal forebrain and medial septal region. The present study investigated the interactions of the muscarinic receptor antagonist scopolamine and the neuropeptide galanin on an operant spatial delayed non-matching to sample task (DNMTS) in rats. Scopolamine administered both intraperitoneally and microinjected into the medial septum impaired performance on DNMTS. Galanin administered alone into the medial septum did not disrupt DNMTS, but potentiated the disruptive effects of intraperitoneal administered scopolamine. These findings raise the possibility that endogenous galanin may exacerbate cognitive impairments associated with forebrain cholinergic deficits.

Acetylcholine↗

PubMed1995

[Effect of scopolamine on the contents of beta-endorphin and oxytocin in hypothalamus, pituitary and plasma in morphine dependent rats].

Male Sprague-Dawley rats weighing 180-220 g were rendered dependent on morphine by repeated injections of morphine in increasing doses for 14 days. 0.3 mg/kg of scopolamine was injected intraperitoneally bid for 3 and 4 days. Control rats were similarly injected with saline. The contents of beta-endorphin (beta-EP) and oxytocin (OT) in hypothalamus, pituitary and plasma were measured by radioimmunoassay. The results showed that both beta-EP and OT in hypothalamus and plasma increased but both were decreased in pituitary in morphine dependent rats (P < 0.01). After scopolamine treatment, the contents of beta-EP increased but OT decreased in hypothalamus (P < 0.01), and both elevated significantly in pituitary (P < 0.01). The results suggested that scopolamine might modulate hypothalamus-pituitary system to affect the release or synthesis of beta-EP and OT in the brain.

Animals↗

PubMed1994

Possible involvement of the activation of voltage-sensitive calcium channels in the ameliorating effects of nefiracetam on scopolamine-induced impairment of performance in a passive avoidance task.

We investigated the effects of various types of calcium channel antagonists on the amelioration by nefiracetam [N-(2,6-dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl) acetamide, DM-9384] of scopolamine-induced impairment of performance in a passive avoidance task in mice. The reversal of the scopolamine-induced impairment of performance by nefiracetam showed a bell-shaped plot. Both i.p. and i.c.v. injection of L-type calcium channel antagonists such as nifedipine and flunarizine attenuated the ameliorating effects of nefiracetam, although diltiazem had no effect. Neomycin, an N-type calcium channel antagonist, also attenuated these effects of nefiracetam in a dose-dependent manner. Further, LaCl3 but not NiCl2 showed inhibitory effects on the amelioration by nefiracetam. These results suggest that the activation of high-voltage-activated, but not low-voltage-activated, calcium channels is involved in the ameliorating effects of nefiracetam on scopolamine-induced impairment of performance in a passive avoidance task.

Animals↗

PubMed1994

Effect of scopolamine on the efflux of dopamine and its metabolites after clozapine, haloperidol or thioridazine.

The extracellular concentrations of dopamine (DA) and its metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), in the striatum and the nucleus accumbens were measured in awake, freely-moving rats. Clozapine (20 mg/kg, i.p.) increased extracellular DA and HVA in both regions but increased DOPAC only in the striatum. Scopolamine (1 mg/kg), although it had no effect by itself in the striatum or nucleus accumbens, inhibited the ability of clozapine to increase extracellular DA, DOPAC and HVA concentrations in the striatum. The clozapine-induced increase in DA in the frontal cortex was not blocked by scopolamine. Haloperidol (1 mg/kg, i.p.) and thioridazine (10 mg/kg, i.p.) also increased extracellular DA, DOPAC and HVA in the striatum, but scopolamine pretreatment did not inhibit these increases. The results suggest that clozapine differs from haloperidol and thioridazine in that the effect of clozapine, but not that of the two neuroleptic drugs, to increase DA release in the striatum acutely depends on muscarinic receptor stimulation. These results suggest that clozapine, despite its strong muscarinic antagonist properties, does not produce full blockade of muscarinic receptors in vivo in the striatum. The interaction of clozapine with the cholinergic system in the striatum could be relevant to its lack of ability to produce extrapyramidal symptoms or tardive dyskinesia.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1977

Effects of reticular stimulation, d-amphetamine and scopolamine on acetylcholine release from the hippocampus of brainstem transected cats.

The effects of i.v. and topical scopolamine and i.v. d-amphetamine were determined on spontaneous release of acetylcholine (ACh) from the dorsal hippocampus of the cat. Animals were prepared under halothane anesthesia with a brainstem transection and either intact or transected fornices. Subsequently, they were placed on room air. ACh was bioassayed using the leech muscle preparation. The amount of spontaneous ACh release varied markedly with each animal with a range of 10 to 21.5 ng/cm2/10 min. There was no mean difference in ACh release between midpontine pretrigeminal and midcollicular brainstem transections. Stimulation of the mesencephalic reticular formation with 300 H/e every sec for 9 sec produced a 28% increase in ACh release from the hippocampus in midpontine pretrigeminal brainstem transected preparations. After section of both fornices, spontaneous ACh release was not altered, although the increased release due to reticular formation stimulation was prevented. d-Amphetamine, in doses of 2.5 mg/kg given i.v., also produced an increase in ACh release from the hippocampus in midpontine pretrigeminal brainstem transected preparations. The d-amphetamine increase in ACh release from the hippocampus was also prevented when both fornices were cut. In contrast, scopolamine in doses of 0.75 mg/kg i.v. increased ACh release in midpontine pretrigeminal brainstem transected cats, either with intact or cut fornices. Topical application of scopolamine (1 microng/ml) to the hippocampus (with or without cut fornices) caused an increase in hippocampal ACh release. It is concluded that the spontaneous or evoked release of ACh from the cat hippocampus provides additional evidence for its role as a neurotransmitter.

Acetylcholine↗