Evaluation of antimotion sickness drug side effects on performance

This project has employed a computerized pursuit meter which has a high correlation with operational performance (2) to test the principal antimotion sickness drugs. Proficiency scores on the pursuit meter task were improved over placebo scores in subjects with d-amphetamine 10 mg and 5 mg, the combination of promethazine 25 mg plus scopolamine 0.4 mg with d-amphetamine 10 mg, and the combination of scopolamine 1 mg with d-amphetamine 10 mg. Scores were not significantly different from placebo scores in tests with scopolamine 0.25 mg, 0.5 mg, or 0.6 mg; marezine 50 mg; meclizine 50 mg; or dimenhydrinate 50 mg. This was also true for the combination of scopolamine 1 mg with d-amphetamine 5 mg, and that of promethazine 25 mg with d-amphetamine 10 mg. A statistically significant decrement of performance scores was seen with scopolamine 1 mg or 0.8 mg, and with promethazine 25 mg oral or 25 mg I.M. The combination of promethazine 25 mg with scopolamein 0.4 mg, and that of promethazine 25 mg oral plus 25 mg I.M. with d-amphetamine 10 mg, also gave significant decrements from placebo scores. These results indicate that selected doses and combinations of antimotion sickness drugs can be used without loss of operational proficiency.     

Nuclear medicine evaluation of motion sickness and medications on gastric emptying time

Diminished gastric motility and lack of bowel sounds have been observed in astronauts aboard the Space Shuttle (4). In this study subjects were given scopolamine 0.6 mg with d-amphetamine 5 mg with and without neostigmine 15 mg. Neostigmine 15 mg alone was also compared with placebo for effect on gastric emptying time. In an additional test, subjects performed head movements in a rotating chair to an end-point of motion sickness short of vomiting. Ten ounces of isotonic saline containing 1 mCl of Tc 99mDPTA was ingested 2 h after the medications and immediately after rotation. The counts from stomach contents were monitored with a Picker small field of view gamma camera every 30 s for 1 h. Gastric motility was inhibited by scopolamine and amphetamine with 14% residual count at the end of 1 h. When neostigmine was added to this combination the results were in the placebo range. Motion sickness produced a profound inhibition of gastric emptying with a 47% residual count. The results indicate that the gastric stasis encountered in space is due mainly to motion sickness with a minimal contribution from the antimotion sickness drugs.     

Differential effects of scopolamine and amphetamine on microcomputer-based performance tests

Scopolamine (1.0 mg) and d-amphetamine (10 mg) were administered alone and in combination to 16 subjects (medical students), randomly assigned to testing sessions in a fully crossed-over (Latin square) within-subjects design. After being practiced to stability, 9 performance tests from a menu of portable microcomputer-based tests were administered double-blind over 4 weekly treatments (including a placebo). Differential effects of drugs on performance were found. Motor and perceptual speed tests appeared enhanced by d-amphetamine and not degraded by scopolamine. Two of the five cognitive tests showed reductions with scopolamine. The findings are discussed in connection with using a menu of performance tests that can have diagnostic significance for assessment of drug treatments. The effects of scopolamine in this study and others are considered in terms of a model which implies that magnitude of performance deficit depends on performance type (cognitive, motor, self-report) and dosage level. Applying the model, we offer the following summary: below 0.15 mg scopolamine is without any effect; below 0.50 mg, the effect is limited, but can be revealed by some sensitive, complex performance tests and self-report; above 1.0 mg, the effect is likely to impact on operational efficiency.     

Therapeutic effects of antimotion sickness medications on the secondary symptoms of motion sickness

In addition to nausea and vomiting, motion sickness involves slowing of brain waves, loss of performance, inhibition of gastric motility and the Sopite Syndrome. The therapeutic effects of antimotion sickness drugs on these reactions were evaluated. The subjects were rotated to the M-III end-point of motion sickness. Intramuscular (IM) medications were then administered. Side effects before and after rotation were reported on the Cornell Medical Index. Brain waves were recorded on a Grass Model 6 Electroencephalograph (EEG), and gastric emptying was studied after an oral dose of 1 mCi Technetium 99m DTPA in 10 oz. isotonic saline. An increase in dizziness and drowsiness was reported with placebo after rotation. This was not prevented by IM scopolamine 0.1 mg or ephedrine 25 mg. EEG recordings indicated a slowing of alpha waves with some thea and delta waves from the frontal areas after rotation. IM ephedrine and dimenhydrinate counteracted the slowing while 0.3 mg scopolamine had an additive effect. Alterations of performance on the pursuit meter correlated with the brain wave changes. Gastric emptying was restored by IM metoclopramide. Ephedrine IM but not scopolamine is effective for some of the secondary effects of motion sickness after it is established.     

Acupressure and motion sickness

The effectiveness of the "Sea Band" acupressure band compared with placebo and hyoscine (0.6 mg), also known as scopolamine, to increase tolerance to a laboratory nauseogenic cross-coupled motion challenge was assessed using 18 subjects. The results showed that the subjects had a significant increase in tolerance with hyoscine but had no increase in tolerance with the "Sea Band" or placebo. Possible reasons for the failure to show any significant protection from the use of these acupressure bands are insufficient movement of the wrist to provide continuous stimulation, and/or the likelihood that only a minority of the population would show non-negligible benefit as experience with medical acupressure would suggest. The application of transcutaneous electrical nerve stimulation may be worthy of study.     

Coriolis加速度刺激适应豚鼠前庭传出系统神经元活性的变化

目的 探索动物前庭适应产生的神经生理基础。方法 采用胃电图波幅值作为观察植神经反应的指标,利用小剂量、多次重复的Ｃｏｒｉｏｌｉｓ加速度刺激,建立前庭适应动物模型。采用免疫组化染色和显微相对灰度分析方法,观察动物在产生前庭适应前后,以及前庭适应消退后,脑干前庭传出系统神经元细胞活性的变化,及其与胃电图波幅值变化的联系。结果 建模成功豚鼠受到运动刺激时,刺激前后的胃电图波幅相近。在前庭适应的豚鼠身上,其脑干前庭传出系统神经元内胆碱乙酰化酶的含量明显增加;但在前庭适应消退后,这种含量的差别消失。这表明在豚鼠出现适应性时此神经元对于前庭终器感觉细胞的抑制性作用明显增强。结论 脑干前庭传出系统神经元可能通过降低前庭终器感觉细胞向中枢神经系统的信号发放的程度,参与了适应性的产生过程。     

Effects of some motion sickness suppressants on static and dynamic tracking performance

Two studies examined the influence of three established antimotion sickness drugs on tracking performance in static (stationary) and dynamic (angular acceleration) conditions and on visual fixation ability during motion. In Study I, 40 young men were randomly assigned in equal numbers to either a control (lactose placebo), dimenhydrinate (50 mg), promethazine hydrochloride (25 mg), or mixture (25 mg promethazine plus 10 mg d-amphetamine) group. Study II used 30 new subjects equally divided into control, dimenhydrinate (100 mg), and promethazine (50 mg) groups. Following practice, tests were conducted prior to, and 1, 2, and 4 h after drug ingestion. The depressant drugs had little effect on static tracking, but impaired dynamic tracking performance and reduced ability to maintain visual fixation on a localizer/glide slope instrument due to increased ocular nystagmus. The mixture of promethazine plus d-amphetamine produced none of these deleterious effects.     

盐酸苯环壬酯对空晕病易感飞行学员脱敏习服的影响

目的 观察盐酸苯环壬酯（PCH）对空晕病易感习行学员脱敏习服的影响以及停药后有无反弹现象。经阶梯式累加科里奥加速度刺激评定为空晕病易感者的18名飞行学员为受试对象,以Graybiel急性运动病诊断标准MⅢ为终点的科里奥利加速度耐受值为评定指标。18名飞行学员随机分为两组,服用PCH组和服用安慰剂组。两组飞行学员都接受以科里奥利加速度为刺激源的脱敏习服训练。PCH（3mg）和安慰剂分别在训练前1h口服。观察两组脱敏训练过程的判别,并在PCH停药后连续3d测试有无反弹现象。结果 PCH可明显加速脱敏习服训练过程,停药后未见得里奥利加速度耐力下降和易感性反弹现象。结论 PCH具有加束脱敏习服训练过程的作用,而没有东莨菪碱停用后易感性反弹的类似效应出现。     

Vestibular training promotes adaptation of multisensory integration in postural control

BackgroundPostural stability depends on the integration of the multisensory system to produce motor outputs. When visual and somatosensory input is reliable, this reduces reliance on the vestibular system. Despite this, vestibular loss can still cause severe postural dysfunction. Training one or more of the three sensory systems through vestibular habituation and adaptation can alter sensory weighting and change postural behavior.AimThe purpose of this study was to assess sensory reweighting of postural control processing after combined vestibular activation with voluntary weight shift training in healthy adults.MethodsThirty-three healthy individuals (18–35 y.o.) were randomly assigned to one of three groups: No training (control), visual feedback weight shift training (WST) coupled with an active horizontal headshake (HS) activity to elicit a vestibular perturbation, or the same WST without HS (NoHS). Training was performed 2x/day, every other day (M, W, F), totaling six sessions. Pre- and post- assessments on the Sensory Organization Test (SOT) were performed. Separate between- and within- repeated measures ANOVAs were used to analyze the six SOT equilibrium scores, composite scores, sensory ratios and center of pressure (COP) variables by comparing baseline to post-training. Alpha level was set at p < .05.ResultsThere was a significant group x session x condition change (p = .012) in the COP multiscale entropy (MSE) velocity sway in the HS group during SOT conditions 5 and 6. Similarly, COP medio-lateral standard deviation sway (ML Std) showed group x session x visual condition (p = .028), due to HS in condition 6 relative to other two groups.ConclusionPostural training can alter sensory organization after a visual feedback-vestibular activation training protocol, suggesting a possible sensory reweighting through vestibular adaptation and/or habituation.SignificanceTranslating these findings into a vestibular-impaired population can stimulate the design of a rehabilitation balance protocol.     

Motion-sickness medications for aircrew: impact on psychomotor performance

INTRODUCTION: Motion sickness remains a significant problem for aircrew both in the flying environment (airsickness) and for aircrew deployed at sea (seasickness). While some anti-motion-sickness medications provide reasonable efficacy, adverse neurocognitive effects limit their use in military personnel engaged in safety-sensitive operational roles such as flying. The purpose of this study was to assess the impact on psychomotor performance of promethazine, meclizine, and dimenhydrinate and to determine if the addition of pseudoephedrine or damphetamine to promethazine would ameliorate its adverse effects. METHODS: There were 21 subjects (11 men, 10 women), aged 22-59, who were assessed for psychomotor performance on 4 tasks as well as with sleepiness and drug side-effects questionnaires. Psychomotor testing was conducted prior to, and for 7 h after, ingestion of a single dose of each of placebo, promethazine 25 mg, meclizine 50 mg, dimenhydrinate 50 mg, promethazine 25 mg plus pseudoephedrine 60 mg, and promethazine 25 mg plus d-amphetamine 10 mg. RESULTS: Relative to placebo, promethazine, meclizine, and promethazine plus pseudoephedrine impaired performance on all four tasks [serial reaction time (SRT), logical reasoning (LRT), serial subraction (SST), and multitask (MT)]. Dimenhydrinate impaired performance on the SRT only. Promethazine plus d-amphetamine did not impair performance on any task nor did it result in increased sleepiness. The times to recovery of normal performance for SRT with promethazine, meclizine, dimenhydrinate, and promethazine plus pseudoephedrine were > 7.25, 7.25, 4.25, and 7.25 h, respectively; for LRT were > 7.25, > 7.25, ns, and 7.25 h; for SST were > 7.25, > 7.25, ns, and 7.25 h; for MT were 7.25, 7.25, ns, and 7.25 h. Recovery times to baseline sleepiness levels for promethazine, meclizine, dimenhydrinate, and promethazine plus pseudoephedrine were 7.25, > 7.25, 6.25, and > 7.25 h. CONCLUSION: Only promethazine plus d-amphetamine was free from impact on psychomotor performance and did not increase sleepiness.     

Motion sickness in cats: a symptom rating scale used in laboratory and flight tests.

The cat is proposed as a model for the study of motion and space sickness. Development of a scale for rating the motion sickness severity in the cat is described. The scale is used to evaluate an antimotion sickness drug, d-amphetamine plus scopolamine, and to determine whether it is possible to predict sickness susceptibility during parabolic flight, including zero-G maneuvers, from scores obtained during ground based trials.     

Treatment of motion sickness in parabolic flight with buccal scopolamine.

Treatment of acute motion sickness induced by parabolic flight with a preparation of scopolamine placed in the buccal pouch was investigated. Twenty-one subjects flew aboard a KC-135 aircraft operated by the National Aeronautics and Space Administration (NASA) which performed parabolic maneuvers resulting in periods of 0-g, 1-g, and 1.8-g. Each subject flew once with a tablet containing scopolamine and once with a placebo in a random order, crossover design. Signs and symptoms of motion sickness were systematically recorded during each parabola by an investigator who was blind to the content of the tablet. Compared with flights using placebo, flights with buccal scopolamine resulted in significantly lower scores for nausea (31%-35% reduction) and vomiting (50% reduction in number of parabolas with vomiting). Side effects of the drug during flight were negligible. We conclude that buccal scopolamine is more effective than a placebo in treating ongoing motion sickness.     

Scopolamine blood levels following buccal versus ingested tablets

Speed of absorption and elimination of an antimotion sickness drug sets limits on the protection afforded. The aim of this experiment was to determine whether a well proven antimotion sickness drug--scopolamine (hyoscine)--could be absorbed more rapidly from buccal tablets than from the standard issue ingested tablets. Plasma scopolamine levels were measured using a radioreceptor assay of repeated blood samples from 10 volunteers, each of whom took buccal and standard ingested tablets (both 0.6 mg scopolamine hydrobromide) on two different occasions, and from a further 8 volunteers following ingestion of a pharmacy-prepared scopolamine capsule (0.6 mg scopolamine hydrobromide). There was no statistically significant speed advantage for the buccal tablet (mean time to peak levels approx 50 min). Individual variation in the speed of scopolamine absorption and rate of elimination (mean half-life approx 170 min) was great. This may account for failure of motion sickness protection in some individuals.     

Effect of transdermally administered scopolamine in preventing motion sickness.

The efficacy of transdermally administered scopolamine was compared with the efficacy of oral dimenhydrinate and placebo therapy in the prevention of motion-induced mausea in a vertical oscillator; medications were administered on a double-blind cross-over basis, with the order of treatments counterbalanced. Thirty-five subjects known to be susceptible to the stimulus were utilized. A placebo effect reduced the motion sickness incidence (MSI) from 100% to 59%. Administration of dimenhydrinate reduced the MSI to 32%, and use of the transdermal therapeutic system scopolamine (TTS-scopolamine) further reduced the MSI TO 16%. TTS-scopolamine afforded 73% protection against motion-induced nausea, compared to 46% protection with dimenhydrinate. The TTS-scopolamine is designed to remain in the body for 72 hours, providing advantages over intramuscular or oral administration of scopolamine, which include reduced daily dosage, and an effective alternate to the gastrointestinal tract for administrating medication at times of gastrointestinal distress.     

Acute mountain sickness; prophylactic benefits of antioxidant vitamin supplementation at high altitude

Acute mountain sickness; prophylactic benefits of Free-radical-mediated damage to the blood-brain barrier may be implicated in the pathophysiology of acute mountain sickness (AMS). To indirectly examine this, we conducted a randomized double-blind placebo-controlled trial to assess the potentially prophylactic benefits of enteral antioxidant vitamin supplementation during ascent to high altitude. Eighteen subjects aged 35 +/- 10 years old were randomly assigned double-blind to either an antioxidant (n = 9) or placebo group (n = 9). The antioxidant group ingested 4 capsules/day(-1) (2 after breakfast/2 after evening meal) that each contained 250 mg of L-ascorbic acid, 100 IU of dl-a-tocopherol acetate and 150 mg of alpha-lipoic acid. The placebo group ingested 4 capsules of identical external appearance, taste, and smell. Supplementation was enforced for 3 weeks at sea level and during a 10-day ascent to Mt. Everest base camp (approximately 5,180 m). Antioxidant supplementation resulted in a comparatively lower Lake Louise AMS score at high altitude relative to the placebo group (2.8 +/- 0.8 points versus 4.0 +/- 0.4 points, P = 0.036), higher resting arterial oxygen saturation (89 +/- 5% versus 85 +/- 5%, P = 0.042), and total caloric intake (13.2 +/- 0.6 MJ/day(-1) versus 10.1 +/- 0.7 MJ/day(-1), P = 0.001); the latter is attributable to a lower satiety rating following a standardized meal. These findings indicate that the exogenous provision of water and lipid-soluble antioxidant vitamins at the prescribed doses is an apparently safe and potentially effective intervention that can attenuate AMS and improve the physiological profile of mountaineers at high altitude.     

Vestibular habituation in student pilots

The dynamics of vestibular nystagmus were measured in 42 military student pilots (age 19 to 21). Their responses were compared with 40 non-flying subjects of similar age who were also fulfilling requirements for the mandatory Swiss military service. The following differences emerged: the time constant of the nystagmus response after vestibular stimulation was shorter (p less than 0.001; t-test) in student pilots, whereas the gain tended to be higher (p less than 0.025). These changes in the response dynamics are attributed to habituation. Student pilots were additionally tested with conflicting visual-vestibular stimulation. Nystagmus response was delayed and attenuated when compared to stimulation in darkness. Under these conditions motion sickness occurred in one third of the subjects. We found no relation between the occurrence of motion sickness and the value of the time constant or gain of vestibular nystagmus. Results show that there is no single "normal" value of vestibular nystagmus. This becomes important when defining "normal" values as opposed to pathological values in vestibular testing.     

动态视功能差异性的探究

目的：通过检测前庭习服前后受试者的动态视力功能,以优化和完善动态视力相关评估标准。方法应用前庭功能检查系统检测16名健康受试者静态及动态视功能。结果当向左、向右摆头速度达到一定速率时,前庭习服前后受试者动态视力存在差异。结论受试者通过前庭习服,前庭系统预刺激后敏感性降低,其动态视力变化情况明显优于习服前,前庭功能适应性锻炼及地面训练对动态视力可能存在影响。     

Transient minor improvement of high altitude headache by sumatriptan

High-altitude headache often fulfills the criteria of migraine. Therefore, we hypothesized that sumatriptan, a 5-HT1 receptor agonist specifically effective for treatment of migraine, would also alleviate high altitude headache. A randomized, placebo-controlled double-blind trial was performed on 29 mountaineers with at least moderate headache on the day of arrival at 4559 m. Fourteen subjects received 100 mg sumatriptan orally and 15 subjects received placebo. Before treatment there were no significant differences between groups regarding rate of ascent, duration and severity of headache, and acute mountain sickness score. All 6 female subjects were randomly assigned to placebo. Absolute values and the reduction of headache scores 1, 3, and 12 h after the administration of sumatriptan did not differ between treatment groups, but headache scores tended to be lower with sumatriptan after 1 or 3 h when compared with placebo. Considering only male mountaineers, there was a significant decrease of headache scores after 1 and 3 h. Because there was only a minor transient amelioration of high altitude headache with sumatriptan, we conclude that 5-HT1 receptors do not play a major role in the pathophysiology of high altitude headache.     

The combined effect of cinnarizine and domperidone on vestibular susceptibility

Four test medications were randomly examined in 25 volunteers for the depressant effect on the labyrinth during stimulation in a rotation chair as well as in a parallel swing. The medications, placebo (pl), Domperidone 30 mg (D), Cinnarizine 40 mg (C) and Touristil 40 mg + 30 mg (C+D), were tested at 1-week intervals, the duration and amplitude of nystagmus having been recorded 15 min, 30 min, 1, 2, 3 and 4 h after intake of the medication. In both tests Touristil (C+D) was significantly (p less than 0.01) to very significantly (p less than 0.0001) more potent, more rapid, and longer working than placebo and the separate components (C) and (D). In addition the working of Touristil was specifically superior to Cinnarizine, when given separately. It appears that the new preparation Touristil approaches the profile of the ideal drug against motion sickness more closely than any other medication.     

Transdermal scopolamine: human performance and side effects

The effect of transdermal scopolamine on performance was tested on 23 naval volunteers. Performance was evaluated by using a battery of professional (naval-related) and cognitive tests. For all tests performed there were no significant differences between the scores obtained in placebo and transdermal scopolamine conditions. These results were in close agreement with subjective estimations of performance. Transdermal scopolamine significantly reduced salivary flow, whereas mood state, visual acuity, and eye accommodation for near vision were not affected. We conclude that transdermal scopolamine administration is not accompanied by decrement in performance abilities and can safely be used by naval crews.