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Effects of a neurotensin analogue (PD149163) and antagonist (SR142948A) on the scopolamine-induced deficits in a novel object discrimination task.

Various lines of evidence suggest a role in cognition for the endogenous neuropeptide, neurotensin, involving an interaction with the central nervous system cholinergic pathways. A preliminary study has shown that central administration of neurotensin enhances spatial and nonspatial working memory in the presence of scopolamine, a muscarinic receptor antagonist which induces memory deficits. Utilizing similar methods, the present study employed a two-trial novel object discrimination task to determine the acute effect of a neurotensin peptide analogue with improved metabolic stability, PD149163, on recognition memory in Lister hooded rats. Consistent with previous findings with neurotensin, animals receiving an intracerebroventricular injection of PD149163 (3 microg) significantly discriminated the novel from familiar object during the choice trial. In addition, a similar dose of PD149163 restored the scopolamine-induced deficit in novelty recognition. The restoration effect on scopolamine-induced amnesia produced by PD149163 was blocked by SR142948A, a nonselective neurotensin receptor antagonist, at a dose of 1 mg/kg (intraperitonial) but not at 0.1 mg/kg. In conclusion, the present results confirm a role for neurotensin in mediating memory processes, possibly via central cholinergic mechanisms.

Adamantane↗

Transdermal scopolamine in drooling.

The effect of oral anticholinergic drugs has been limited in the treatment of drooling. Transdermal scopolamine (1.5 mg/2.5 cm2) offers advantages. One single application is considered to render a stable serum concentration for 3 days. A distinct reduction of basal salivation was demonstrated in an open trial of six healthy volunteers. Eighteen mentally retarded patients with a drooling problem were studied in a double-blind, placebo-controlled cross-over trial. The therapeutic effect of transdermal scopolamine was assessed by a visual analogue scale. Three patients dropped out due to loss of the system. In the remaining 15 patients, the active drug caused a reduction of drooling which was significant in the period from 24 to 72 h. There were few and slight objective signs of unwanted effects. Scopoderm may cause drowsiness and affect tooth health. The management of drooling should primarily be focused on the cause. Sensomotor training is often valuable in cerebral palsy. Factors such as nasal obstruction, mucosal irritation, and drug-induced parkinsonism should be given attention. Sometimes, however, a temporary symptomatic treatment is indicated, for example on special occasions or in order to cure peri-oral skin lesions. Transdermal scopolamine may offer this possibility.

Administration, Cutaneous↗

Premedication with intramuscular dixyrazine: (Esucos). A controlled double-blind comparison with morphine-scopolamine and placebo.

Ninety patients scheduled for general or orthopaedic surgical procedures were randomly assigned to receive one of three i.m. premedications: dixyrazine 0.5 mg kg-1; morphine 0.15 mg kg-1 and scopolamine 0.0065 mg kg-1; or placebo. The premedication was administered and evaluated in a double-blind fashion. The patients were anaesthetized with thiopentone, fentanyl, pancuronium, and ventilated with nitrous oxide in oxygen. The three premedications had no noticeable anxiolytic effect. Although there was no difference in the frequency of observed postoperative nausea and vomiting between the three groups, premedication with dixyrazine nonetheless reduced the patients' experience of postoperative nausea as well as their need for postoperative antiemetics. Although patients in the two treatment groups were significantly more sedated immediately before induction of anaesthesia than patients receiving placebo, the degree of postoperative sedation was similar in all three groups. Morphine-scopolamine caused more postoperative dizziness than dixyrazine and placebo. Lack of recall was produced by both morphine-scopolamine and dixyrazine. It is concluded that premedication with dixyrazine is a useful alternative, especially in patients who have previously experienced postoperative nausea and vomiting.

Adult↗

Rectal versus intramuscular morphine-scopolamine as premedication in children.

Intramuscular morphine-scopolamine for premedication was compared with a hydrogel of the same drugs for rectal administration in 205 healthy children scheduled for minor ENT surgery. The intramuscular dose was 0.15 +/- 0.006 mg x kg-1 compared to 0.25 +/- 0.015 mg x kg-1 rectally. Reaction at administration and anaesthetic induction, incidence of intraoperative airway difficulties, Spo2, ECG changes, postoperative pain and incidence of nausea were recorded. The administration for the rectal hydrogel group worked better and resulted in less postoperative nausea and slightly more postoperative pain. The children's behaviour at anaesthesia induction and the frequency of perioperative complications were similar in both groups. We conclude that for minor ENT surgery on children, premedication with rectal hydrogel of morphine-scopolamine is a good alternative to intramuscular morphine-scopolamine.

Adenoidectomy↗

Transdermal scopolamine for reduction of drooling in developmentally delayed children.

Ten developmentally delayed children with excessive drooling were randomized in a double-blind, placebo-controlled study to assess the efficacy and safety of transdermal scopolamine. Over half of the patients had a statistically significant reduction in drooling, and one-third had cessation of drooling, while wearing the scopolamine patch. This short-term study supports earlier reports of the safety and efficacy of transdermal scopolamine for reducing excessive drooling in developmentally disabled children.

Administration, Cutaneous↗

Effects of NMDA modulation in scopolamine dementia.

D-Cycloserine is a partial agonist at the strychnine-insensitive neuronal glycine receptor and positively modulates the N-methyl-D-aspartate (NMDA) excitatory amino acid receptor. NMDA receptors appear to be important in learning and memory, and D-cycloserine facilitates learning in rats. In man, central cholinergic blockade due to scopolamine administration impairs attention, information processing, and memory for new information, the latter secondary memory impairments resembling those shown in patients with Alzheimer's disease (AD). D-Cycloserine has been studied for its ability to counteract the cognitive decrements produced by scopolamine in young and elderly healthy volunteers. D-Cycloserine specifically antagonized the memory impairments produced by scopolamine. These findings provide evidence of NMDA receptor involvement in human memory and suggest a novel mechanism for alleviation of memory loss associated with aging and dementia.

Adolescent↗

Cholinesterase inhibition in the scopolamine model of dementia.

Scopolamine produces a satisfactory model of the attentional and secondary memory deficits seen in Alzheimer's disease (AD) that can be used to screen compounds for potential therapeutic usefulness. Physostigmine, which is known to enhance memory in AD, produced marked and widespread antagonism of the scopolamine-induced impairments, indicating the sensitivity of the model and establishing its relevance for the clinical situation. HP 029, a novel anticholinesterase, also exhibited widespread potency in the model, and in an international trial with patients with AD, it subsequently showed improvement on similar measures, demonstrating the predictive use of the scopolamine model.

Alzheimer Disease↗

Effects of atropine, scopolamine and xylazine on the placement of an orally administered magnet in cows.

This study was carried out to determine whether the administration of atropine, scopolamine or xylazine to cows before the administration of a magnet orally would help to position it in the reticulum. The transit time of the magnet through the oesophagus was also measured. Sixty Swiss Braunvieh cows were examined by radiography and ultrasonography to locate the reticulum. They were then divided into six groups of 10. Before the administration of the magnet, a control group received 4 ml saline solution subcutaneously, one group received 0.10 mg/kg of atropine subcutaneously, a second received 0.05 mg/kg of atropine intravenously, a third received 0.15 mg/kg of scopolamine intravenously, a fourth group received 0.02 mg/kg of xylazine intravenously, and the cows in the fifth group were positioned so that their forelimbs were 30 cm lower than their hindlimbs during the administration of the magnet. The passage of the magnet through the oesophagus was timed with a stopwatch and monitored with a compass. In the control group the magnet passed through in less than 60 seconds, but in four of the cows receiving either atropine or xylazine intravenously, or having their forelimbs positioned lower than their hindlimbs, it took longer than 60 seconds. In the cows receiving atropine subcutaneously or scopolamine intravenously, it took the same time as in the control group. All the cows were radiographed one-and-a-half hours after the administration of the magnet to determine its location. In seven of the 10 cows in the control group, the magnet was located in the reticulum, but in the other three it was in the cranial dorsal blind sac of the rumen. In the other five groups the magnet was located in the reticulum of between four and seven of the 10 cows, but in the cranial dorsal sac of the rumen, the rumen or in other sites in the other cows.

Administration, Oral↗

Local infusion of scopolamine into intraparietal cortex slows covert orienting in rhesus monkeys.

There is accumulating evidence to suggest that cholinergic neurotransmission may play an important role in visuospatial attention, but the brain sites at which acetylcholine modulates attention are not well understood. The present work tested the hypothesis that the cholinergic influences within the intraparietal cortex are necessary for normal attentional shifting (covert orienting) in nonhuman primates. Two rhesus monkeys were trained to perform a visual, cued target detection task for liquid reinforcement. The animals pressed a lever to produce a visual display in which a central fixation point was flanked by two circles. Shortly after fixation was established, one of the circles brightened (cue), and a target appeared subsequently within one of the circles. Detection was signaled by a manual response and the reaction time to the appearance of the target was recorded. Four types of trials were presented. For valid cue trials, the cue and target were at the same spatial location; for invalid cues, cue and target were in opposite hemifields; for double cues, both cues were brightened but the target appeared in either the left or right circle; in no-cue trials, the cue was omitted. We localized the intraparietal region by recording attention-related, cellular activity with intracerebral microelectrodes. Among visually responsive cells in this area, valid cues presented to the receptive fields of visual neurons enhanced the responses to target stimuli in about half the cells and inhibited those responses in the remainder. In addition, some cells showed longer response latencies to invalid cues than to valid cues. We then infused scopolamine into attention-related activity sites and assessed its effect on performance. Scopolamine produced a dose-dependent increase in reaction times and decrease in performance accuracy that lasted more than 1 h. Neither vehicle injections in the same locations nor scopolamine outside the physiologically defined area produced any significant change in behavior. Under our conditions of measurement, we conclude that activity mediated by muscarinic cholinergic receptors within the intraparietal cortex is necessary for normal covert orienting.

Animals↗

Scopolamine and the sensory conditioning of hallucinations.

By means of a sensory conditioning procedure, auditory 'hallucinations' were produced in a set of subjects by pairing a light and a tone. The effect of two doses of scopolamine on the occurrence of these hallucinations was investigated, and the results showed that they were more likely to occur after scopolamine than when subjects had received a placebo. This change was attributed to the impairment of information processing induced by scopolamine.

Acoustic Stimulation↗

Transdermal scopolamine: effects of single and repeated patches upon psychological task performance.

Scopolamine and placebo transdermal patches were applied on alternating days to 12 normal volunteer subjects. Psychological performance tasks, physiological assessments, a subjective feeling state questionnaire, and a sleep questionnaire were completed each day. Transdermal scopolamine produced significant decrements in memory task performance, daytime feelings of alertness, ease of waking, and alertness following waking, while resting heart rates were lowered. Significant drug x patch number interaction effects were present with memory for new information, letter cancellation omission errors, rapid visual information processing reaction time, and self-rated ease of getting to sleep, but there was no consistent pattern to the changes following successive patches. Visual problems (blurred vision, longer visual near point) increased following successive scopolamine patches, but the changes in task performance were not related to these visual changes.

Administration, Cutaneous↗

Effect of scopolamine on spontaneous yawning in men.

The effect of scopolamine hydrobromide (0.4 mg s.c.) on spontaneous yawning was studied in 16 male volunteers in a double-blind study. Scopolamine (or placebo) was given 60 min before (-60 min) placebo (physiological saline s.c.) (time 0 min) and yawning monitored from -15 to +60 min by recording displacement of the lower jaw and storing the traces on diskettes. After placebo, the number of yawns was 5.3 +/- 1.4 (means +/- SE) and after scopolamine pretreatment 4.3 +/- 1.6 (p = NS). Drowsiness was assessed with the Stanford Sleepiness Scale and the Analog Sleepiness Scale at -15, 0, +20, +40, +60 min. There was no significant correlation between total sleepiness scores (area under the curve, 0 min to +60 min), peak sleepiness score or peak increment in sleepiness score and number of yawns on either scale. These data suggest that (a) spontaneous yawning in man is not mediated by a central muscarinic cholinergic link, and (b) the assumed relationship between drowsiness and yawning remains to be verified experimentally.

Adult↗

Transdermal scopolamine for the reduction of postoperative nausea in outpatient ear surgery: a double-blind, randomized study.

We evaluated the effect of transdermal scopolamine on the incidence of postoperative nausea and vertigo after outpatient ear surgery (exploratory tympanotomy, mastoidectomy, or endolymphatic sac and oval and round window surgery) in a double-blind, placebo-controlled study. A transdermal patch containing either scopolamine (n = 19) or placebo (n = 20) was placed behind the nonsurgical ear 2 h before surgery. Anesthesia was induced with thiopental (4-6 mg/kg intravenously [i.v.]), sufentanil (0.5 microgram/kg i.v.), and vecuronium (0.1 mg/kg i.v.) and maintained with isoflurane (0.2%-2%) and nitrous oxide (70%) in oxygen. Patients were observed postoperatively in the recovery room and after discharge for 72 h. There was no significant difference between groups with respect to time in recovery room, time to discharge, incidence of in-house nausea, vomiting, amount of antiemetics required, or postoperative visual analog scale (VAS) scores while in the hospital. After discharge, there were lower VAS nausea scores (by repeat measures analysis, P < 0.05) and a lower reported incidence of nausea (31% vs 62%; P < 0.05) and vertigo (6.2% vs 25%; P < 0.05) in the active patch group versus the placebo group. There was a higher incidence of dry mouth in the active patch group (44% vs 25%). Seven patients did not complete the study due to failure to keep the patch in place or failure to return the diary from home; and one patient from the placebo patch group was admitted for uncontrolled nausea and vomiting. The authors concluded that transdermal scopolamine is effective in reducing, but not eliminating, postoperative nausea and vertigo after discharge in outpatient ear surgery.

Administration, Cutaneous↗

Panax ginseng extract improves the scopolamine-induced disruption of 8-arm radial maze performance in rats.

The effects of Panax ginseng ethanol extract and its water (WSF)- and lipid-soluble (LSF) fractions on the scopolamine-induced disruption of radial maze performance in rats were examined. Ginseng root was refluxed with ethanol, and WSF and LSF were prepared from this ethanol extract. Scopolamine (0.075-0.3 mg/kg, i.p.) dose-dependently impaired the maze performance. However, the oral administration of Panax ginseng ethanol extract and WSF (2-8 g dried root/kg) 90 min before testing improved the maze performance disrupted by scopolamine (0.3 mg/kg) in a dose-dependent manner, but LSF failed to attenuate the disruption. These data suggest that ginseng extract possesses a beneficial effect regarding spatial cognitive impairment and that the water-soluble fraction of ginseng extract mainly contributes to the effect of the ethanol extract.

Animals↗

[Chirality of natural products: hyoscyamine and scopolamine].

Monthly changes of the content-ratio between S-(-)- and R-(+)-hyoscyamine as well as those between S-(-)- and R-(+)-scopolamine in the leaves of Datura metel L. cultivated in the field, were quantitatively analyzed by the use of HPLC with a chiral adsorbent. It was found that S-(-)-isomer was predominant for hyoscyamine and the ratio of R-(+)-isomer gradually increased during the growth, whereas in the case of scopolamine, S-(-)-isomer was the sole one found throughout the cultivation period. The 1H-NMR study in the CD3OD solution has suggested that S-(-)-hyoscyamine (1) and S-(-)-scopolamine (2) take a "face-to-face" conformation between their tropane skeletons and the benzene rings of the tropic acid moieties. In the presence of an equimolar NaOD in the CD3OD solution, the racemization at C-2' of 1 and 2 proceeded more rapidly than the hydrolysis at the tropic acid ester bond, presumably due to the steric hindrance caused by their "face-to-face" conformations. In the D2O and H2O solutions, on the other hand, the racemization and the hydrolysis of 1 proceeded smoothly, while those of 2 did not occur. It has been supposed that these individual reaction manners are ascribable in considerable extent to the different basicity of N atom in each tropane skeleton of 1 and 2 and to stronger intramolecular hydrogen bond occurring between the carbonyl oxygen at C-1' and the hydroxyl group at C-3' in the tropic acid moiety of 1.

Atropine↗

[A simple multiple maze test to estimate learning and memory in mice: application to the effect of scopolamine on learning and memory].

The apparatus consists of a home cage, a maze cage and a starting box. A maze with four right-middle-left decisions was placed in the maze cage. The starting box was attached and a water tap was placed at an area corresponding to the entrance of the maze. The exit of the maze and the home cage are connected with a tunnel. Food was placed in the home cage. 1) Mice were housed for 10 hr a day in the apparatus and then removed to another cage for fasting. One trial a day was carried out after fasting for more than 12 hr. In each trial, a mouse was put at the starting box, and then the number of errors (entering a blind alley) and the time until the mouse reached the home cage were counted. The mouse passed through the maze with a small number of errors and time. 2) Administration of scopolamine (0.125-0.5 mg/kg, i.p.) to a mouse that had mastered the maze transiently disturbed the maze performance dose-dependently. 3) Mice were housed for 4 hr a day. Scopolamine (0.25 mg/kg, i.p.) was administered either before or after the housing. Scopolamine disturbed the maze performance in the case of both procedures. These results suggest that the method is useful for estimating the memory in mice.

Animals↗

Determination of the effectiveness of components of the herbal medicine Toki-Shakuyaku-San and fractions of Angelica acutiloba in improving the scopolamine-induced impairment of rat's spatial cognition in eight-armed radial maze test.

The improving effects of various components of Toki-Shakuyaku-San (TSS) and fractions isolated from Angelica acutiloba Radix (Toki) on scopolamine-induced spatial memory impairment were investigated in eight-armed radial maze. The scopolamine-induced memory impairment was characterized by prominent increase of error choices in addition to decreased correct choices. Toki, Cnidium officinale Rhizoma (Senkyu), Poria cocos Hoelen (Bukuryo), Alisma orientale Rhizoma (Takusha), and Atractylodes lancea Rhizoma (Sojutsu) increased the correct choices, while only the Toki, Sojutsu, and Takusha decreased the error choices. No effect was produced by Paeonia lactiflora Radix (Shakuyaku). Investigation of effects of fractions isolated from Toki revealed that its activity mainly resided in the butanol layer and its contents of N-methyl-beta-carboline-3-carboxamide and amines. Moreover, the alkaloid, internal and external solutions (containing poly-, di-, and monosaccharides) obtained by dialysis with Visking cellophane tubing also improved the memory. However, no improving properties were detected for methanol and hexanol layers, L-(-)-tryptophan, L-arginine, L-(-)-lysine, and choline chloride. The results showed that the TSS components could improve the reference and working memory impaired by scopolamine. The improving effect of TSS is produced greatly by the Toki component, the activity of which was greatly produced by the fraction extracted by butanol.

Angelica↗

Physostigmine's effect on diminished fetal heart rate variability caused by scopolamine, meperidine and propiomazine.

Physostigmine was given to 17 patients in labor, previously given scopolamine alone or meperidine and propiomazine in combination, to ascertain its effect on reversing the loss of fetal heart rate variability caused by the administration of these drugs. The results of the study indicated that scopolamine in doses of 0.65 to 1.08 milligrams diminished fetal heart rate variability in all 7 patients and physostigmine reversed this loss of fetal heart rate variability in all 7 patients within 4 to 17 minutes after injection of the first dose of physostigmine. Similar results were noted in 10 patients with the combination of meperidine, 50 mg, and propiomazine, 20 mg. It seems tenable from this study that physostigmine does cross the placental barrier and enters the fetal circulation and that this usually occurs within 3 to 17 minutes with an average of approximately 9 minutes. In the healthy fetus the loss of fetal heart rate variability caused by scopolamine, meperidine or propiomazine can be reversed by the use of physostigmine and this reversal seems abrupt and clinically measurable on the fetal monitor print out.

Adolescent↗