Anti-motion Sickness Research Articles

Effects of anti-motion sickness drugs on motion sickness in rats.

Pica, the eating of nonnutritive substances such as kaolin, can be induced by rotation in rats. We used this rotation-induced pica as a behavioral index of motion sickness in rats and examined whether diphenhydramine, methamphetamine and scopolamine, which are anti-motion sickness drugs for humans, are effective for reducing motion sickness in rats. Intraperitoneal injection of diphenhydramine or methamphetamine suppressed the rotation-induced kaolin intake of rats. Intraperitoneal injection of scopolamine had no effect on the rotation-induced kaolin intake, but its transdermal administration reduced this kaolin intake. These findings show that human anti-motion sickness drugs also prevent motion sickness in rats. Since the pharmacological mechanisms for preventing motion sickness in rats and humans are similar, we conclude that rats are a suitable animal model for use in studies on putative anti-motion sickness drugs.

M.I.T./Canadian vestibular experiments on the Spacelab-1 mission: 4. Space motion sickness: symptoms, stimuli, and predictability.

Space sickness symptoms were observed by 4 specially trained observers on Spacelab-1. Three reported persistent symptoms, and vomited repeatedly during the first and/or second day of flight. Head movements on all axes were provocative, particularly in pitch and roll. Head acceleration data recorded from 2 symptomatic crewmen showed that after several hours of physical activity in orbit, symptoms appeared, and thereafter both crewmen were compelled to limit head movements. Firm body contact with motionless surfaces helped alleviate symptoms. When crewmembers floated into unfamiliar body orientations in the cabin, inherent ambiguities in static visual orientation cues sometimes produced spatial reorientation episodes which were also provocative. Symptoms largely resembled those of other forms of prolonged motion sickness, superimposed upon other symptoms attributable to fluid shift. All 4 eventually used anti-motion sickness drugs. When they did, vomiting frequency was reduced. By the 4th day, symptoms subsided, and head accelerations again increased in magnitude and variability. Sickness intensity in orbit was not predicted by statistically concordant results of 6 acute preflight susceptibility tests. However, results from a longer duration preflight prism goggles test showed an apparent correlation. All subjects were asymptomatic making head movements in parabolic flight 4 days after the mission, but not 1 year later. Overall, results support the view that space sickness is a motion sickness.

Dexamethasone mimicks the antimotion sickness effects of amphetamine and scopolamine

Based on preliminary suggestions that individual differences in susceptibility to stressful motion might be related to physiological differences in responses of the hypothalamic-pituitary-adrenal axis, we tested the efficacy of dexamethasone and metyrapone in subjects exposed to cross-coupled accelerative semicircular canal stimulation on a rotating chair. Subjects given 0.5 mg of dexamethasone every 6 h for 48 h could endure 80% more stressful motion ( P = 0.03) in a within-subjects design study, whereas, no improvement followed treatment with 750 mg of metryapone every 4 h for 24 h. The efficacy of dexamethasone might be explained in terms of its neurochemical actions on several neurotransmitter systems which are also modulated by such classical antimotion sickness drugs as amphetamine and scopolamine. Because dexamethasone induces adaptive changes within the central nervous system it may prove superior to scopolamine and amphetamine which possess significant side effects, are short acting, and rapidly tolerated.

Histaminergic mechanism of motion sickness. Neurochemical and neuropharmacological studies in rats.

Rats were rotated about two parallel axes to produce motion sickness, and the histamine levels in their hypothalamus and pons-medulla oblongata were measured. Rotation for 60 min induced kaolin intake, which is a behavioral index of motion sickness in rats, and increased the histamine levels in the hypothalamus and pons-medulla oblongata, the highest levels occurring after 15 min of rotation. In bilaterally labyrinthectomized rats, no rise in histamine level was observed. alpha-Fluoromethylhistidine (alpha-FMH), which depletes the neural component of histamine in the brain, suppressed kaolin intake induced by rotation. These findings demonstrated that the histaminergic neuron system contributes to development of motion sickness, and suggested that alpha-FMH may be effective as an anti-motion sickness drug.

Muscarinic cholinergic receptors in area postrema and brainstem areas regulating emesis

Central cholinergic pathways modulate both the perception of excessive motion stimuli and the expression of motion sickness symptoms, such as nausea and vomiting. Specific brainstem areas which mediate motion-induced emesis include the area postrema (AP), vagal nuclear complex (VNC), reticular formation (RF) at the site of the vomiting center, and the vestibular complex (VC). In this report, histological studies indicated the cellular organization of brainstem structures mediating emesis was similar in bovine and squirrel monkey brain. The objective of this study was to characterize biochemical and pharmacological properties of muscarinic cholinergic receptors assayed by 3H-QNB binding in these regions of bovine brainstem. Scatchard analyses of specific 3H-QNB binding showed an uneven distribution of muscarinic receptors, with high densities of sites in VNC and AP, intermediate levels in RF and lowest receptor concentrations in VC. Dissociation constants for 3H-QNB, measured in saturation and kinetic experiments, were similar in all brainstem regions. The pharmacological potency of cholinergic agonists and antagonists was the same as reported for muscarinic receptors labeled in other brain areas or peripheral organs. Several drugs which potently inhibited 3H-QNB binding in bovine brainstem also exhibited antiemetic activity in a squirrel monkey model of motion-induced emesis. The antimotion sickness effects of these drugs may be due, in part, to their antagonism of muscarinic receptors in brainstem areas regulating emesis.

Motion sickness: A modulatory role for the central cholinergic nervous system

The present review has extended the general theory of motion sickness proposed by Wood and Graybiel [135,136] by identifying specific neurophysiological mechanisms that are involved in motion sickness and by interpreting the actions of both scopolamine and amphetamine as effective anti-motion sickness drugs within this neurophysiological context. The neurochemical and neurophysiological effects of scopolamine have been reviewed in relationship to central cholinergic pathways. Cholinergic pathways have been associated with both the perception and expression of normal and excessive levels of motion stimuli. New approaches to the problem of the prevention of motion sickness have been considered. Efferent nicotinic innervation at the primary sensory hair cells and the medial vestibular nucleus were identified as sites where modulation by cholinergic drugs might exert a beneficial influence. However, it was generally conceded that the complexity of the cholinergic system and the interaction of scopolamine with that system left open the possibility that pharmacological doses of drugs specific to the cholinergic system might exert significant modulatory influences at alternative sites, as well.

いわゆる“乗り物酔い”防止薬に関する検討 スコポラミンの相乗効果について

A study comparing the efficacy of an anti-motion sickness drug, Scopolamine, when administered in combination with an antihistaminic drug is presented. The possibility of classifying the subjects into two groups i. e. with vulnerability to or tolerance for motion sickness is also discussed.The subjects in this study were young students who had a normal vestibular function. Three groups of 10 subjects each were used and the following drugs were evaluated.1. Dimenhydrinate, 50 mg.2. Diphenhydramine salicylate, 40mg.3. Scopolamine hydrobromide, 0.1mg and dimenhydrinate, 50mg.Each group received the acceleration and deceleration rotation testy and the sum of the values of the theoretical threshold (expressed by the angular deviation of the cupulaendolymph system) for the clockwise and counterclockwise rotation is evaluated after drug administration. The following items were pointed out in this study.1. When a combination of dimenhydrinate and scopolamine was used, a large increase in effectiveness in preventing motion sickness was suggested.2. Subjects vulnerable to motion sickness were differentiated from the normal subjects with their lower values than theoretical threshold value of 1.44°. This vulnerable group is more susceptible to the antimotion sickness drugs in the above mentioned combination than the other tolerant group.

Antimotion sickness drug efficacy.

The principal medications available for the prevention of motion sickness were tested for their relative efficacy in a Navy National Aeronautics and Space Administration program at Pensacola, Fla. The drugs were tested on the human centrifuge, at sea, in the air, and in zero gravity flights. The results of this research indicated that drugs with central anticholinergic actions such as scopolamine, promethazine, dimenhydrinate (Dramamine), cyclizine (Marezine), and meclizine (Bonine) were effective in increasing resistance to motion sickness. Drugs with central effects which enhanced the action of norepinephrine were also effective. These included dextroamphetamine sulfate (Dexedrine) and ephedrine. It is recommended that all antimotion sickness drugs be taken at least one hour before exposure to motion. For severe conditions of motion it is recommended that one of the following drug combinations be used: (1) scopolamine, 0.6 mg, plus dextroamphetamine sulfate, 5 mg, or (2) promethazine, 25 mg, plus ephedrine, 25 mg. Moderate conditions may be controlled by dimenhydrinate, 50 mg, and in mild conditions such as automobile travel, cyclizine, 50 mg, or meclizine, 50 mg, may be sufficient. The proper dose of an effective antimotion sickness drug given at the proper time will protect most susceptible patients from motion sickness. After motion sickness has developed, intramuscular injections of promethazine or scopolamine have a therapeutic effect.

Coping with space motion sickness in Spacelab missions

A substantial number of persons, around 75%, making their first transition into orbital flight will need to adapt to this unique environment. The two most powerful instruments in the prevention of space motion sickness reside in the selection process and in acquiring adaptation-prelaunch. Today, neither of these means is practical. One logical alternative is to administer preventative medication to all or none. One candidate drug is a high-potency transdermal therapeutic system (TTS)-scopolamine. This is marketed in the nature of a patch that is affixed to the skin behind the ear 12 hr before need and delivers scopolamine into the blood stream for three days. We are systematically evaluating all claims for its high potency and low side effects. We are also evaluating new antimotion sickness remedies and new combinations of homergic drugs.

Influence of a GABA agonist, diazepam, on the vestibuloocular reflexes of the rabbit

We have studied the influence of intravenously administered diazepam on the horizontal (HVOR) and vertical (VVOR) vestibuloocular reflexes of the rabbit, and on the activity of single secondary vestibular neurons. The HVOR was evoked by sinusoidal oscillation of rabbits on a rate table (0.01−0.8 Hz, ± 10 deg) and eye movements were measured with an infrared light projection technique. The gains of the HVOR and VVOR (evoked eye velocity/head velocity) were reduced by diazepam injections of 5 μg/kg. The dose required to produce a 50% reduction in HVOR gain was 500 μg/kg. The time required to reduce the HVOR gain to 50% of its maximal reduction at a dose of 400 μg/kg (0.4 Hz, ± 10 deg) was 60 sec. Intravenous injections of diazepam (20–100 μg/kg) caused a decreased sensitivity of secondary vestibular neurons to sinusoidal angular accelerations. This reduction in sensitivity was observed in secondary neurons which were excited by ipsilateral or contralateral angular acceleration. Thus, diazepam in low doses depresses the vestibuloocular reflex and this reflex depression can be observed at the level of the secondary vestibular neuron. These data suggest that diazepam might be effective as an acute anti-motion sickness agent.

Pharmacological study of anti motion sickness preparations

Pharmacological study of anti motion sickness preparations

Space motion sickness

Space motion sickness, presumably triggered by sudden entry into a weightless environment, occurred with unexpected frequency and severity among astronauts who flew the Skylab missions. Recovery from symptoms was complete within 3–5 days, and as revealed by the Skylab M131 Human Vestibular Function Experiment, all crewmembers were immune to experimentally induced motion sickness after mission day 8. This syndrome has been recognized as a possible threat to the early mission well-being and operational efficiency of at least some individuals who will fly space missions in the future. The causes of space motion sickness are not clearly understood, nor have satisfactory methods been identified to date for its prediction, prevention and treatment. In order to minimize the potential impact of this syndrome on Space Shuttle crew operations the National Aeronautics and Space Administration has organized a broad program of inter-disciplinary research involving a large number of scientists in the United States. Current research on the etiology of space motion sickness is based to a large extent on the so called sensory conflict theory. Investigations of the behavioral and neurophysiological consequences of intralabyrinthine, as well as intermodality sensory conflict are being performed. The work in this area is being influenced by the presumed alterations that occur in otolith behavior in weightlessness. In addition to sensory conflict, the possible relationship between observed cephalad shifts of body fluids in weightlessness and space motion sickness is being investigated. Research to date has failed to support the fluid shift theory. Research underway to identify reliable test methods for the prediction of susceptibility to space motion sickness on an individual basis includes attempts to (a) correlate susceptibility in different provocative environments; (b) correlate susceptibility with vestibular and non-vestibular response parameters, the latter including behavioral, hemodynamic and biochemical factors and (c) correlate susceptibility with rate of acquisition and length of retention of sensory adaptation. Controlled studies are also being performed during parabolic flight as a means of attempting to validate predictive tests for susceptibility to this syndrome. Research to develop new or improved countermeasures for space motion sickness is underway in two primary areas. One of these involves anti-motion sickness drugs. Significant achievements have been realized with regard to the identification of new highly efficacious drug combinations, dose levels and routes of administration. Although pronounced individual variations must be accounted for in selecting the optimum drug and dose level, combinations of promethazine plus ephedrine or scopolamine plus dexidrine are presently the drugs of choice. Work is also underway to identify side effects associated with anti-motion sickness drug use and to identify new drugs which may selectively modify activity in central neural pathways involved in motion sickness. In addition to research on drugs, efforts are being made to develop practical vestibular training methods. Variables which influence rate of acquisition of adaptation, length of retention of adaptation and transfer of protective adaptation to new environments are being evaluated. Also, included in this area is the use of biofeedback and autogenic therapy to train individuals to regulate autonomic responses associated with motion sickness. While valuable new knowledge is expected to evolve from these combined research programs, it is concluded that the final validation of predictive tests and countermeasures will require a series of controlled space flight experiments.

Antimotion sickness and antiemetic drugs.

The antimotion sickness drugs protect a high percentage of individuals from becoming motion sick if the proper drug is given in sufficient dosage 1 to 2 hours before exposure, and an effective blood level is maintained throughout the required period. The stresses due to motion encountered in most civilian travel such as air, automobile and on moderate seas can be counteracted effectively by the antihistaminic group of antimotion sickness preparations. Dimenhydrinate 50mg, cyclizine 50mg, and meclozine 50mg are examples of this group. Doses can be given three times a day during prolonged exposure. If the conditions are more stressful, promethazine 25mg alone or combined with ephedrine 25mg can be given. Highly susceptible patients and very rough conditions may require hyoscine (scopolamine) 0.3 to 0.6mg with or without dexamphetamine 5 to 10mg. Promethazine or hyoscine in the above dose can be given IM as a therapeutic measure after motion sickness has developed, and both produce drowsiness which may be beneficial for the passengers but would be contraindicated for the crew. All of the antimotion sickness drugs with the exception of dextroamphetamine and ephedrine are effective antiemetics against vomiting of toxic origins. However, the most effective antiemetics in this situation are the phenothiazines such as perphenazine, prochlorperazine and thiethylperazine. Ranking next in effectiveness is trimethobenzamide which is followed by the antihistaminic antimotion sickness drugs. Promethazine ranks with other phenothiazines as an antiemetic and is the only phenothiazine also effective against motion sickness. Morning sickness usually is self limiting but if antiemetics are required, promethazine and dimenhydrinate may be used.

Motion sickness: Some theoretical and practical considerations

This paper reviews some of the more important theoretical and practical considerations relating to the widespread problem of motion sickness. A brief outline is given of the sensory rearrangement theory which seeks to define the essential nature of the nauseogenic stimulus. A wide range of provocative situations is classified as involving either a visual-inertial conflict, or a canal-otolith conflict or both. A number of behavioural measures by which the passenger can minimise the risk of motion sickness are described. Also considered are quantitative studies of vertical oscillatory motion, factors influencing motion sickness susceptibility (sex, age, exposure-history, receptivity and adpatability and personality characteristics), and the paper concludes with recommendations regarding the most effective use of anti-motion sickness drugs.

Space motion sickness medications: Interference with biomedical parameters

The possibility that drugs administered to Skylab 3 (SL-3) and 4 (SL-4) crewmen for space motion sickness may have interfered with their biomedical evaluation in space was investigated. Healthy volunteers received combinations of Scopolamine/Dexedrine for four days in regimens similar to those used in these missions. Urine samples, heart rate, body temperature, mood and performance were analyzed for drug-related changes. Twenty-four hour urine samples were analyzed by the same procedures as those used to analyze the flight samples. Hormone concentrations determined included cortisol, epinephrine, norepinephrine, aldosterone and antidiuretic hormone (ADH). In addition, volume, specific gravity, osmolarity, sodium (Na), potassium (K), calcium (Ca), magnesium (Mg), chloride (Cl), inorganic phosphate, uric acid and creatinine were measured. Performance was not affected by the Scopolamine/Dexedrine. The drug combination increased daily mean heart rate (HR) significantly in all the subjects and daily mean rectal temperature (RT) in some of the subjects. A 2–4 hr phase shift in the HR circadian rhythm was also observed which indicates that internal circadian synchrony was disturbed by the drugs. Psychological and subjective evaluation indicated that the subjects could usually identify which days they were given the drugs by an increase in tension and anxiety, decreased patience, restlessness, decreased appetite, difficulty in sleeping and feelings of increased heart rate and body temperature. Urinary electrolytes were not changed significantly by the drug, but marked and significant changes occurred in urine volume and hormone excretion patterns. Scopolamine/Dexedrine caused consistent elevations in urinary cortisol and epinephrine and a transient elevation in ADH. Norepinephrine excretion was decreased, but there was no significant change in aldosterone excretion or in 24 hr urine volume. A comparison of these findings with the first four days of inflight data from the SL-3 and SL-4 missions leads to the conclusion that the dramatic increases in aldosterone excretion during the first three days of spaceflight probably can be directly attributed to weightlessness, whereas the antimotion sickness medication could have substantially contributed to the early increased excretion of epinephrine and cortisol during these missions.

Anti-Motion Sickness Medications in Dysmetric Dyslexia and Dyspraxia

Anti-Motion Sickness Medications in Dysmetric Dyslexia and Dyspraxia

Sea Motion Simulation, Very Low Frequency Vibration, and Motion Sickness

The office of Naval Research/Human Factors Research (ONR/HFR) Motion Generator was designed with three degrees of freedom (heave, pitch, and roll) to simulate the motion of an air-sea craft in varying ocean conditions through Sea State 5. Recent upgrading of the device has provided the capability for simulating the motion of advanced design sea craft as well as certain aspects of vertical motion common to land, sea, and air vehicles. Since 1968, the simulator has been used for investigation of the following topics: (1) basic research to provide equations for the prediction of motion sickness incidence based on parameters of vertical linear oscillation, (2) crew performance during simulated motion of two types of proposed naval vessels, and (3) evaluation of the efficacy of antimotion sickness medications in alleviating the symptoms of motion sickness. This simulator provides the opportunity for future research on the effects of motion on physiological and psychological processes as well as task performance.

Stress modification of the toxicity of antimotion sickness drugs and aspirin.

The effect of environmental temperature on the toxicity of cyclizine, trimethobenzamide, and Aspirin were studied in mice. LD50s were compared at 30 degrees C (warm), 22 degrees C (normal), and 15 degrees C (cool). At 30 degrees C the toxicity of all three drugs increased, with that to aspirin being affected most. Cooling decreased the toxicity of cyclizine and had no significant effect on that of trimethobenzamide or Aspirin. These findings indicate that alterations in environmental temperature markedly affect drug toxicity. They emphasize that such alterations, and particularly increases in temperature, do not have to be particularly drastic, but that "mild' variations in the environment are effective in altering an animal's sensitivity to a drug.

Effects of Diphenidol on the Central Vestibular and Visual Systems of Cats

It is well known that anticholinergic agents such as atropine and scopolamine are effective as anti-motion sickness drugs, however, the mechanism of action in the vestibular system is inadequately understood. It has been demonstrated by several investigators (1–5) that neurons in the vestibular nucleus are excited by local application of acetylcholine. Gerebtzoff (6) has sfibwn a histochemical localization of cholinesterase in the vestibular nucleus of cats. Contents of the enzyme were relatively high in the superior and lateral parts of the nucleus, but low in the medial and inferior parts. According to the hypothesis of Wood and Graybiel (7), motion sickness occurred when activation of the central cholinergic system disturbed the balance of vestibular reactions, and protection would be achieved by utilizing anticholinergic drugs.

Effects of diphenidol on the central vestibular and visual systems of cats.

It is well known that anticholinergic agents such as atropine and scopolamine are effective as anti-motion sickness drugs, however, the mechanism of action in the vestibular system is inadequately understood. It has been demonstrated by several investigators (1-5) that neurons in the vestibular nucleus are excited by local application of acetylcholine. Gerebtzoff (6) has shown a histochemical localization of cholinesterase in the vestibular nucleus of cats. Contents of the enzyme were relatively high in the superior and lateral parts of the nucleus, but low in the medial and inferior parts. According to the hypothesis of Wood and Graybiel (7), motion sickness occurred when activation of the central cholinergic system disturbed the balance of vestibular reactions, and protection would be achieved by utilizing anticholinergic drugs. Diphenidol (1, 1-diphenil-4-piperidine-1-butanol) which is related chemically to trihexylphenidil and chlorphenianol has been found effective in the treatment of motion sickness (8-11). Leonard et al. (12) have shown that diphenidol is equal in anti-emetic potency to chlorpromazine and that diphenidol has a greater selectivity of pharmacological action in experimental animals. The present experiments using cats were designed to study the effects of diphenidol on evoked responses in the central vestibular and visual systems.