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Separating the effects of response rate and reinforcement frequency in the rate-dependent effects of amphetamine and scopolamine on the schedule-controlled performance of rats and pigeons.

Rats and pigeons responded under three-component multiple schedules of food reinforcement. Each component was associated with a separate stimulus condition and a schedule that arranged food delivery intermittently for appropriately spaced responding. In the experiment with pigeons, three response rates were maintained with equal reinforcement frequency in the three components. With rats, the lowest response rate was associated with a higher reinforcement frequency. The effects of d-amphetamine in rats (0.05-0.6 mg) and pigeons (0.1-3.0 mg) were closely associated with the dose, and with the response rates that occurred under nondrug control conditions. Small doses of d-amphetamine increased low response rates proportionately more than moderate rates; moderate rates were increased proportionately more than were high rates. With larger doses, low rates were decreased proportionately less than were moderate rates, which in turn were decreased proportionately less than were high rates. Similar relations between drug effects and control rates were obtained in rats with scopolamine (0.0125-0.4 mg), with the exception that constant effects appeared at doses of 0.1 mg and greater. The present experiments, through manipulating response rate independently of reinforcement frequency, show that the rate-dependent effects of d-amphetamine and scopolamine are primarily response-rate-dependent drug effects.

Administration, Oral↗

Infrared identification test for scopolamine as the hydrobromide.

The method of preparation of scopolamine hydrobromide affects the infrared (IR) spectrum of the product. A column chromatographic procedure is used to both isolate the drug from tablets and injections and form the hydrobromide salt. This yields reproducible IR spectra and thus constitutes an identity test for scopolamine hydrobromide.

Chromatography↗

[Reactive fractal dimension in the release of scopolamine bromide from hydrogel].

First-order release kinetics is characterized by a linear dependence of the release rate on the released amount of the active ingredient, the triple of the absolute value of the exponent of the exponential function expressing the reactive fractal dimension DR. Scopolamine bromide release from hydroxypropylmethylcellulose hydrogel was first expressed by first-order kinetics with an estimated DR ranging from 2.98-3.00. The employment of an exponential equation with the exponent of release n renders it possible to make an assumption about the mechanism of release. Within a range of n = 0.505-0.550, estimated DR = 2.46-2.94. In this region, release by means of the mechanism of Fick's diffusion prevails. DR = (3/n)-3 generally holds true for the relationship between both variables, which makes it possible to use the knowledge gained in the experimental influencing of the exponent of release in the examination of the relationship between the reactive fractal dimension and the mechanism of release of scopolamine bromide from hydrogel. An increase in the exponent of release markedly decreases the corresponding values of reactive fractal dimension.

Chemistry, Pharmaceutical↗

[Protective effects of scopolamine on rabbits with acute brain injury].

OBJECTIVE: To study the protective effects of scopolamine (Sco) (a muscarinic receptor antagonist) on rabbits with acute brain injury, and preliminarily explore the roles of acetylcholine (ACh) in the early pathologic changes of traumatic brain injury(TBI). METHODS: The model of acute brain injury was established by a free-falling device, and the rabbits received Sco intraperitoneally at 5 minutes and 2 hours after brain injury respectively. Transcranial Doppler (TCD) was used to monitor cerebral blood flow velocity (CBV) and pulsatility index (PI) of middle cerebral artery (MCA). The levels of Ca2+, the activities of superoxide dismutase (SOD), the contents of malondiadehyde (MDA) and Evans blue (EB) were measured, and the pathological changes were observed in brain tissue. RESULTS: This model consisted with the pathologic changes of accelerated brain injury. Sco reduced the levels of Ca2+, EB and MDA, increased the activities of SOD, and improved cerebral blood flow following brain injury. CONCLUSIONS: In the early stage of brain injury, ACh can cause neuron calcium overload, oxide free radical reaction, cerebral vasospasm, and increase blood-brain barry(BBB) permeability. Scopolamine, a muscarinic receptor antagonist, can improve these pathologic changes. As a result, Sco has protective effects on brain tissue injury.

Acetylcholine↗

Effects of intrahippocampal injections of N-methyl-D-aspartate receptor antagonists and scopolamine on working and reference memory assessed in rats by a three-panel runway task.

In order to elucidate the roles of hippocampal N-methyl-D-aspartate-type excitatory amino acid receptors in working and reference memory in rats, the effects of intrahippocampal injections of selective and competitive N-methyl-D-aspartate receptor antagonists such as CGS 19755 (cis-4-phosphonomethyl-2-piperidine carboxylic acid), 3-[(+-)-2-carboxypiperazin-4-yl]propyl-1-phosphonic acid and 2-amino-5-phosphonovaleric acid on this behavior were examined with a three-panel runway task. The results were compared with the effect of the muscarinic receptor antagonist scopolamine. In the working memory task, CGS 19755 and 3-[(+-)-2-carboxypiperazin-4-yl]propyl-1-phosphonic acid at 10 and 32 ng/side, injected bilaterally into the dorsal hippocampus before testing, produced a significant increase in the number of errors (attempts to pass through two incorrect panels of the three panel-gates at four choice points). This also occurred after the rats were given systemic injection of these drugs at 3.2 and 10 mg/kg. In the reference memory task, neither CGS 19755 nor 3-[(+-)-2-carboxypiperazin-4-yl]propyl-1-phosphonic acid affected the number of errors, whether given at doses up to 32 ng/side intrahippocampally or up to 10 mg/kg systemically. Working memory errors also increased significantly after intrahippocampal injections of d-2-amino-5-phosphonovaleric acid at 100 and 320 ng/side, but were not affected by I-2-amino-5-phosphonovaleric acid at doses up to 1 microgram/side. On the other hand, intrahippocampal scopolamine at 1.0 and 3.2 micrograms/side increased significantly working memory errors, without affecting reference memory errors.(ABSTRACT TRUNCATED AT 250 WORDS)

2-Amino-5-phosphonovalerate↗

Histaminergic response to Coriolis stimulation: implication for transdermal scopolamine therapy of motion sickness.

The blood levels of histamine and 5-hydroxytryptamine (5-HT) in 10 subjects, with or without administration of the transdermal therapeutic system of scopolamine (TTS-S), were measured following motion sickness (MS) induced by Coriolis stimulation. Histamine and 5-HT were assayed using the fluorometric method. The results demonstrated that the blood levels of histamine increased significantly following MS and were even higher in the subjects using TTS-S, but we found neither significant changes in the blood levels of 5-HT following MS nor any effect of TTS-S on it. The results suggest that histamine contributes to the development of MS, and scopolamine may exert its anti-MS action by affecting the histaminergic system as well as the acetylcholinergic system; there may not be a definite relation between 5-HT and the development of MS.

Administration, Cutaneous↗

Scopolamine raises cardiac demand in the elderly during gastrointestinal endoscopy.

BACKGROUND/AIMS: We measured changes in cardiopulmonary function of elderly patients during upper gastrointestinal endoscopy to examine the effects of antispasmodics. METHODOLOGY: This study was conducted on 174 subjects older than 60 years (101 male and 73 female, mean age 71.0). Subjects were divided into 3 groups based on the antispasmodic used for pre-medication: 76 received recombinant glucagon (Group G); 63 scopolamine butylbromide (group B); and 35 had no antispasmodic (group N). After informed consent a pulse oximeter was used to measure heart rate and oxygen saturation at five points during the endoscopic procedure. RESULTS: Maximum heart rate increase and oxygen saturation decrease occurred in all groups when the endoscope passed through the esophago-cardiacjunction. Heart rate was significantly higher in group B than G or N after administration of antispasmodic drugs. CONCLUSIONS: Scopolamine butylbromide should be administered with caution in upper gastrointestinal endoscopy of elderly patients because it may increase cardiac load.

Aged↗

[Determination of scopolamine and atropine in Flos Daturae by RP-HPLC].

OBJECTIVE: To develop a quantitative analytical procedure of scopolamine and atropine in Flos Daturae using RP-HPLC. METHOD: The two alkaloids were separated on a Hypersil BDS C18 column (4.6 mm x 250 mm, 5 microm) with a mobile phase of 0.02 mol x L(-1) sodium acetate buffer (containing 0.02% triethanolamine and the pH was adjusted to 6.0 with acetic acid)-methanol (60:40) and a detection wavelength of 215 nm. The flow rate was 1.0 mL x min(-1) and the column temperature was maintained at room temperature. RESULT: The mean recovery was (99.6 +/- 1.8)% for scopolamine and (100.4 +/- 1.5)% for atropine. CONCLUSION: This method was simple, accurate and sensitive.

Atropine↗

Scopolamine-induced alterations in predatory behaviour pattern in cats.

Predatory behaviour in its full pattern (i.e., following the mouse, killing it and consuming the carcass) was tested in semi-natural conditions in cats. Consumption of minced horse meat was tested as well. Centrally acting scopolamine hydrobromide injected i.p. did not suppress predatory motivation, since following the prey and killing it were preserved. The executory phase of predation (i.e., the killing grip) was severely disturbed and the consumption of the mouse as well as meat was totally inhibited. Peripherally acting scopolamine methylnitrate administered into another group of cats under the same conditions generally did not affect predatory pattern, though meat and mouse consumption was disturbed to some extent. It is concluded that central muscarinic involvement in predatory behaviour in cats is limited to sensorimotor control of jaw movements.

Animals↗

A kampo prescription, shimotsu-to, improves scopolamine-induced spatial cognitive deficits in rats.

The effect of a Kampo (traditional Chinese medicine) prescription, Shimotsu-to, on spatial cognitive deficits produced by scopolamine was examined using an eight-arm radial maze and a T-maze. Scopolamine (SCOP; 0.075-0.3 mg/kg, ip) dose-dependently disrupted the radial maze performance. Single doses of Shimotsu-to (0.5 and 1.0 g/kg, po) as well as physostigmine (0.15 and 0.3 mg/kg, ip) improved the SCOP (0.3 mg/kg)-induced performance deficits in a dose-dependent manner. Shimotsu-to administered for 1 week in drinking water (0.5 and 1.0 g/kg/day) also exhibited dose-dependent reversal of SCOP-induced impairments in the radial maze performance. The same treatment improved SCOP (0.2 mg/kg)-induced impairments in T-maze delayed alternation performance. These data clearly demonstrated the beneficial effects of Shimotsu-to on spatial cognition.

Administration, Oral↗

Comparative studies on the influence of ONK (N(5-hydroxynicotinoil) glutamic acid), piracetam and meclofenoxate on the learning- and memory-impairing effect of scopolamine, clonidine, and methergoline.

The effects of the new compound N(5-hydroxynicotinoil)glutamic acid (ONK) in comparison with the well-known nootropic drugs piracetam and meclofenoxate on cognitive functions impaired by scopolamine, clonidine or methergoline were examined in albino rats and mice. The changes in learning and memory were studied by the two-way active avoidance "shuttle-box", passive avoidance "step-down" in rats and passive avoidance "step-through" in mice. The present results showed that ONK (50 mg/kg) injected intraperitoneally (i. p.), piracetam (800 mg/kg) and meclofenoxate (100 mg/kg) administered orally once daily for 5 days before training completely antagonized the scopolamine-provoked amnesia in step-through-trained mice. ONK (50 mg/kg) administered i. p., piracetam (600 mg/kg) and meclofenoxate (100 mg/kg) administered orally once daily for 5 days before training abolished the memory-impairing effect of clonidine in shuttle-box-trained rats and the amnestic effect of methergoline in step-down trained rats. The observed antiamnestic effects of the nootropic drugs studied are probably realised through their influence on cholinergic, noradrenergic and serotoninergic neurotransmission. The favourable effect of ONK on cognition might be of interest for therapeutic practice.

Animals↗

[Transdermal therapeutic system of scopolamine (TTS-S) in the prevention of sea sickness and its mechanism of action].

The efficacy of transdermal therapeutic system of scopolamine (TTS-S) in the prevention of sea sickness and the extent of its side effects were evaluated in 130 male healthy sailors (volunteers) in a placebo-controlled, double-blind, randomized study. TTS-S or transdermal placebo (TD-P) were placed behind ears 12 hours before departure and removed 72 hours later. It was found that the severity of motion sickness in the TTS-S group was significantly milder than that in the TD-P group. The TTS-S had no statistically significant side effects when compared with the TD-P. The levels of histamine in the blood of 10 subjects, with or without TTS-S, were measured following experimental motion sickness induced by Coriolis test, and the induced optokinetic rotational nystagmus was recorded. The results demonstrated that the level of blood histamine increased after motion sickness, it was higher in the subjects with TTS-S, and there was no significant difference for the optokinetic rotational nystagmus between groups. These findings suggested that histamine contribute to the development of motion sickness and scopolamine may play anti-motion sickness action by blocking the H1-receptor.

Administration, Cutaneous↗

Prochlorperazine and transdermal scopolamine added to a metoclopramide antiemetic regimen. A controlled comparison.

Cisplatin-induced nausea and vomiting occurs both acutely and over a prolonged period of time. These symptoms may be incapacitating and are frequently given as a reason to discontinue therapy. We compared prochlorperazine and transdermal scopolamine when added to a standardized metoclopramide antiemetic regimen. Twenty-seven patients receiving cisplatin at 100 mg/m2 were randomly assigned to one of the two treatment arms. Patients were observed during chemotherapy and answered a standard questionnaire 24-26 hours later. Among similar treatment groups no differences were seen regarding the number of emetic events, level of nausea, degree of sedation or overall acceptability of one treatment arm or another. While not superior to prochlorperazine, transdermal scopolamine is a useful antiemetic agent and can be combined with metoclopramide in an attempt to reduce cisplatin-induced nausea and vomiting. Further evaluation of this approach is needed.

Administration, Cutaneous↗

[Effect of scopolamine and picrotoxin on the learning-dependent long-term synaptic potentiation].

The purpose of this study was to investigate the effects of microinjection of scopolamine, a M-cholinergic antagonist and picrotoxin, a GABA-ergic antagonist into the rat hippocampal CA3 area on the learning-dependent long-term potentiation (LDLTP) during the establishment, extinction and re-establishment of conditioned drinking response. Following stimulation of the perforant path, field potentials of hippocampal CA3 of freely moving rats were recorded. The results were as follows: the synaptic efficacy and the development of LDLTP in hippocampal CA3 were depressed significantly by scopolamine, but the extinction of LDLTP was accelerated. Picrotoxin significantly enhanced synaptic efficacy and facilitated the development of LDLTP, but it depressed the extinction of LDLTP. Meanwhile, the establishment or extinction of drinking conditioning was correspondingly depressed or accelerated. Moreover, the development of LDLTP and its extinction preceded the development and extinction of drinking conditioning. The results provide further evidence indicating that LDLTP might be one of the neuronal mechanisms underlying behavioral learning and memory. Moreover, it seems that M-cholinergic receptors and GABA-ergic receptors in rat hippocampal CA3 area are involved in the development and retention of LDLTP.

Animals↗

Effects of single administration of scopolamine, physostigmine and their combination on biogenic amine levels in rat brain.

There were studied the changes of norepinephrine and dopamine levels in the brain cortex, the brain stem and hypothalamus of rats after the application of scopolamine, physostigmine and their combination. The application of scopolamine (0.5 mg/kg) or physostigmine (1.0 mg/kg) increased the levels of NE and in many cases statistically significantly. The simultaneous application of both drugs was manifested by less marked or neglectable changes of NE and DA levels in comparison with the control group.

Animals↗

Reversal of scopolamine-induced alterations of choline transport across the blood-brain barrier by the nootropics piracetam and pramiracetam.

The choline transport across the blood-brain barrier was studied in nine brain regions of male Wistar rats after treatment with scopolamine, piracetam and pramiracetam, respectively. 14-Day treatment with scopolamine (0.5 mg/kg/d) elicited an increase of the extraction and the PS-product (permeability-surface area) of choline which was prevented by coinjection of piracetam or pramiracetam (100 mg/kg/d). In addition, the cerebral blood flow was increased by both nootropics. Differences between various brain regions were found in both choline transport and cerebral blood flow. It is supposed from the results that the choline transport is regulated by cholinergic innervation of the brain endothelial cells and that the nootropics used may act via alterations of the brain choline metabolism.

Animals↗

[Effect of scopolamine on the memory of exploratory behavior in the mouse].

In the present work it has been evaluated the action of scopolamine on the extent of exploration in mice, whose exploring behaviour had been already earlier examined. Such behaviour has been evaluated using a hole-board. The goal has been to detect the influence of the substance on the short-term memory of mice. The method used has shown to be effective. By the exam of the results of this work it can be concluded that the scopolamine at a dose of 1 mg/kg has an evidence effect of short-time memory in mice by causing a hypomnesia.

Animals↗