Doi:10.1016/j.autneu.2006.07.019

Autonomic Neuroscience: Basic and Clinical 129 (2006) 67 – 76 Department of Psychology, University of Westminster, 309 Regent Street, London W1B 2UW, U.K.
Motion sickness can be caused by a variety of motion environments (e.g., cars, boats, planes, tilting trains, funfair rides, space, virtual reality) and given a sufficiently provocative motion stimulus almost anyone with a functioning vestibular system can be made motion sick.
Current hypotheses of the ‘Why?’ of motion sickness are still under investigation, the two most important being ‘toxin detector’ and the ‘vestibular–cardiovascular reflex’. By contrast, the ‘How?’ of motion sickness is better understood in terms of mechanisms (e.g., ‘sensoryconflict’ or similar) and stimulus properties (e.g., acceleration, frequency, duration, visual–vestibular time-lag). Factors governing motionsickness susceptibility may be divided broadly into two groups: (i) those related to the stimulus (motion type and provocative property ofstimulus); and (ii) those related to the individual person (habituation or sensitisation, individual differences, protective behaviours,administration of anti-motion sickness drugs). The aim of this paper is to review some of the more important factors governing motionsickness susceptibility, with an emphasis on the personal rather than physical stimulus factors.
2006 Elsevier B.V. All rights reserved.
Keywords: Motion sickness; Vestibular; Individual differences; Evolution; Personality; Pharmacology; Perception toxic effects of potentially harmful substances that it mayhave ingested (The “toxin detector” More than two thousand years ago the Greek physician hypothesis proposes that the brain has evolved to recognise Hippocrates observed that ‘… sailing on the sea proves that any derangement of expected patterns of vestibular, visual, and kinaesthetic information as evidence of central nervous Indeed the term ‘nausea’ derives from the Greek root word system malfunction and to initiate vomiting as a defence ‘naus’, hence ‘nautical’ meaning a ship. The last hundred years against a possible ingested neurotoxin, i.e., it provides a innovation of transport and industry have extended the range ‘backup’ to the main toxin detector system of chemorecep- of provocative motion environments, to cars, tilting trains, tors of the afferent vagal nerves and the chemoreceptor funfair rides, aircraft, weightlessness in outer-space, virtual trigger zone of the brainstem. According to this hypothesis, reality, and simulators. The general term ‘motion sickness’ is motion sickness in pedestrian man or other animals is simply best applied across all of those stimulus specific terms such as the inadvertent activation of this ancient defence reflex by car-sickness, air-sickness, space-sickness or sea-sickness.
the sensory conflicts induced by the novel altered visual and The primary functions of the vestibular system are spatial force environments of sea, air, land transport or virtual orientation, maintenance of balance, and stabilising of vision reality. This evolutionary-based hypothesis is consistent with through vestibular–ocular reflexes. An additional vestibular the observation that motion sickness is evolutionarily well function has been proposed, which is that it acts as a toxin preserved from man down to the level of the fish (ironically, detector. Thus, the evolutionary purpose of what we call fish can become seasick during aquarium transport) ( ‘motion sickness’ is postulated to be the same as for any ). It is also consistent with the observation emetic response, which is to protect the organism from the that people who are more susceptible to motion sickness arealso more susceptible to toxins, chemotherapy, and post- operative nausea and vomiting (e.g., ). Finally, Tel.: +44 207 911 5000x2127; fax: +44 207 911 5174.
this theory has been experimentally tested with evidence of 1566-0702/$ - see front matter 2006 Elsevier B.V. All rights reserved.
J.F. Golding / Autonomic Neuroscience: Basic and Clinical 129 (2006) 67–76 reduced emetic response to challenge from toxins after (qualitative types of stimuli, physical characteristics, engi- neering standards, sensory conflict, etc) is much better An alternative hypothesis is based on the observation that tilt understood. The variety of stimuli that can provoke motion stimulation of the otoliths in the cat, which transduce linear accelerations, provoke a pressor response (increased blood The key observation is that the physical intensity of the pressure and cardiac output) mediated via vestibular–cardio- stimulus is not necessarily related to the degree of vascular projections. It has been proposed that motion sickness nauseogenicity. For example, with optokinetic stimuli the is caused by the inappropriate activation of such vestibular– motion is implied but not real, as when a person sitting at the cardiovascular reflexes ”… the vestibular and visual systems … front in a wide screen cinema experiences self-vection and influence autonomic control for the purpose of maintaining ‘cinerama sickness’ despite the lack of any motion in the real homeostasis during movement and changes in posture… motion physical world. In this example, the vestibular and somato- sickness results from an aberrant activation of neural pathways sensory systems are signalling that the person is sitting still, that serve to maintain a stable internal environment and it is not a but the visual system is signalling illusory movement or self- poison response to eliminate toxins from the body, as has been vection. Consequently the generally accepted explanation of the ‘how’ of motion sickness is based on some form of somewhat similar, non-functional explanation has been pro- sensory conflict or sensory mismatch. The sensory conflict or sensory mismatch is between actual versus expected invariant regarded as referred visceral discomfort after activation of patterns of vestibular, visual and kinaesthetic inputs vestibular autonomic reflexes due to the convergence of vestibular and autonomic afferent information in the brainstem conflicts between rotational accelerations sensed by the and cerebellum. The vestibular–cardiovascular reflex hypoth- semi-circular canals and linear-translational accelerations esis has a good historical pedigree in the 19th Century concept (including gravitational) sensed by the otoliths. A variety of of ‘cerebral anaemia’ as the cause of motion sickness detailed models have been developed to explain the nature of More recent support comes from an observation that sensory conflict or sensory mismatch (e.g., cerebral hypoperfusion preceded nausea during gravito-inertial as well as simplified rule based models. With force variation induced by centrifugation ).
regard to the latter, proposed a useful set of However there is a considerable overlap between sick and non- simple rules which if broken, will lead to motion sickness: sick individuals’ pressor responses to the gravito-inertial forcevariation induced by parabolic flight (). The Rule 1. Visual–vestibular: motion of the head in one importance of the vestibular–cardiovascular reflexes in main- direction must result in motion of the external taining blood pressure seems limited since bilateral labyrinthec- tomised patients’ pressor responses to rapid tilts are onlyminimally slower than normals (<500 ms) ).
The importance of such a hypothesis is undermined also by the observation that these patients do not appear to be fainting frequently as they adjust their posture during everyday activity Cars, coaches, tilting trains, ski, camels, as they walk around, lay down and stand up. Moreover, although not a formal disproof, this hypothesis does not predict Boats, ferries, survival rafts, divers’ the relative nauseogenicity of the various gravity and body referenced directions of nauseogenic provocative motion, which Transport planes, small aircraft, hovercraft, would be expected to alter blood pressure ( Both the so-called toxin detector and vestibular–cardio- ‘haunted swing’, simulators, virtual reality vascular reflex hypotheses remain in contention to provide explanations for the ‘why’ of motion sickness. Another pseudo-Coriolis, reversing prism spectacles hypothesis, which has received less attention, postulates that Cross-coupled (Coriolis), low frequencytranslational oscillation (vertical or horizontal), motion sickness is a punishment system which has evolved to discourage development of perceptual–motor pro- counter-rotation, g-excess in human centrifuges grammes that are inefficient or cause spatial disorientation Emetic toxins, chemotherapy, post operative nausea and vomiting (PONV), extreme arousal favours the toxin detector hypothesis.
‘Laboratory’ stimuli evoking motion sickness are simply refined elements of those provocative stimuli found in the outside world. ‘Optokinetic’ stimuliare classed separately since they do not need additional physicaltransportation of the person under all definitions, although some might be Although the ‘Why?’ of motion sickness is uncertain (see also classed under ‘Laboratory’. ‘Correlated’ stimuli are included to indicate above), the ‘How?’ of motion sickness mechanisms the basic evolutionary functions served by nausea and vomiting.
J.F. Golding / Autonomic Neuroscience: Basic and Clinical 129 (2006) 67–76 Rule 2. Canal–otolith: rotation of the head, other than in the movements, and duration of exposure. Unfortunately these horizontal plane, must be accompanied by appro- are often particular to a given class of motion device or even priate angular change in the direction of the gravity a particular laboratory and the procedures used. Conse- quently, they are not generalizable for a standard.
Rule 3. Utricle–saccule: any sustained linear acceleration is It is only with low frequency translational motion, which due to gravity, has an intensity of 1 g and defines is a major source of motion sickness in land vehicles, ships, and aircraft, that models are sufficient to provide engineeringdesign parameters (exposure time, acceleration, frequency) In other words, the visual world should remain space and be incorporated for standards regulated by the Interna- stable, and gravity should always point down and average tional Standards Organisation (ISO). This success is seen in the International Standards Organisation standard for human exposure to whole-body vibration, part of which deals with rule. This is that there is only one conflict of interest, motion sickness produced by low frequencies ( between the subjective expected vertical and the sensed ). The frequency weighting function is of great vertical. However, although this single rule appears simple, theoretical as well as applied interest.
the underlying model is very extensive, as are all the models using or implying frames of reference.
The application of such rules to explain the mechanism of motion sickness in any given environment can be complex (< 1 Hz) are more nauseogenic than higher frequencies and because multiple stimuli and conflicts may be involved. One that nauseogenicity increases as a function of exposure time example may suffice. Airsickness in a pilot produced by the and acceleration intensity. Nauseogenicity peaks at the low flight of an agile military aircraft may be due to several frequency motion of around 0.2 Hz. Such low frequency sources. Flying straight and level through air turbulence motions are present in transportation in ships, coaches, frequently encountered close to the ground or sea, produces aircraft flying through air turbulence, and on camels and low frequency translational oscillation of the aircraft, which elephants, all of which can provoke motion sickness.
may cause airsickness. During co-ordinated aircraft turns However, during walking, running, horse riding, riding off- there may be simultaneous provocation from the four road trail bikes, etc., the frequencies are higher than 1 Hz.
following sources: (a) visual–vestibular mismatches as the Consequently, although these motions can be quite severe pilot senses ‘down’ to remain through the axis of the body (capable of bruising the person), they are not nauseogenic.
but the external visual world to be tilted; (b) sustained Hypotheses for the frequency dependence of nauseogeni- changes in the scalar magnitude of gravito-inertial force due city of translational oscillation are a phase-error in signalling to centripetal acceleration; (c) cross-coupling (Coriolis) due motion between canal–otolith and somatosensory systems to head movements during rotation of the aircraft if the turn is tight enough; and (d) also the g-excess illusion if the pilot dependent phase-error between the sensed vertical and the tilts the head during increased gravito-inertial force.
subjective or expected vertical ). It has Whereas there has been much success in explaining the also been proposed that a zone of perceptuo–motor mechanisms of motion sickness, progress has been more ambiguity around 0.2 Hz triggers sickness, since at higher limited in providing quantitative models to predict the frequencies imposed accelerations are usually interpreted as severity of nausea and the incidence of vomiting. In virtual translation of self through space, whereas at lower reality systems (and simulators), self-vection and poor eye frequencies imposed accelerations are usually interpreted collimation may be an important provocative stimulus, but as a shift in the main force vector, i.e., tilt of self with respect phase lag between real motion and the corresponding update of the visual display may be equally or more important.
Compensatory vestibular–ocular reflexes to head move- cross-over between these two interpretations and, thus, a ments are as fast as 10 ms or so, consequently visual update frequency region of maximal uncertainty concerning the lag disparities not much longer than this may be easily correct frame of reference for spatial orientation.
detectable by subjects. If update lags are much longer thanthis then they may provoke sickness, since it has been shown 3. Limitations to the concept of motion sickness that virtual reality sickness has been induced with update lags as short as 48 ms (). These numbers at leastgive some potential for a future quantitative standard. In Individual differences in motion sickness susceptibility other circumstances, for example during cross-coupling are great. However, the concept of motion sickness (Coriolis) or off-vertical axis rotation, quantitative estimates susceptibility must acknowledge the multi-factorial nature for predicted motion sickness may be made based on of motion sickness susceptibility itself. At least three parameters such as rotational velocity rates, incremental processes are thought to be at work: initial sensitivity to rates of increase in rotation, angles of tilt or head motion, rate of natural adaptation, and the ability to retain J.F. Golding / Autonomic Neuroscience: Basic and Clinical 129 (2006) 67–76 protective adaptation in the longer term ( motion sick using real motion, although obviously optoki- ). Moreover, correlations among various types of netic stimuli (are ineffective. With regard to the motion challenges are not high ), implying contribution of aspects of other individual differences in differential sensitivity in individuals to different types of vestibular function to motion sickness susceptibility, the motion; e.g., the correlation between susceptibility to evidence is limited. Otolith asymmetry between left and right translational versus cross-coupled (Coriolis) motion can labyrinths, as measured during parabolic flight, has been proposed as an indicator of susceptibility for space sickness self-report questionnaires, designed to assess susceptibility to motion sickness, suggests the existence of independent sensation of unsteadiness and tilting of the ground when a latent susceptibilities to different types of provocative sailor returns to land. A similar effect is observed in environments, usually forming factors that might be termed astronauts returning to 1 g on Earth after extended time in transportation by land, air, sea, or funfair rides weightlessness in space. In severe cases this can lead to ). This might seem to contradict the notion of a general motion sickness but symptoms usually resolve within a few motion susceptibility dimension. Nevertheless these appar- hours as individuals readapt to the normal land environment.
ently contradictory views can be argued to be both true, i.e., a Individuals susceptible to mal de debarquement may have general motion susceptibility factor and specific factors reduced reliance on vestibular and visual inputs and exist.1 Other limitations are imposed by the reliability of increased dependence on the somatosensory system for the response to a motion challenge, which may be estimated from repeated exposures in the laboratory to be around more general sense, individual variation in sensory thresh- r = 0.8–0.9. Finally it is worth noting that the concept of olds to angular or translational accelerations does not seem to motion sickness susceptibility may overlap with sickness relate to susceptibility in any obvious fashion. The evidence susceptibility to other, non-motion emetic stimuli. These that individual differences in postural stability or perceptual relationships among susceptibilities to motion sickness, migraine, chemotherapy, post operative nausea and vomiting of motion sickness susceptibility seems limited ( are often used as evidence for the involvement of the ). Similarly, individual variation in the vestib- vestibular system in the response to non-motion emetogenic ular ocular reflex does not seem to be a reliable predictor of susceptibility, although the ability to modify readily the time might reflect individual differences in excitability of a constant of vestibular ‘velocity store’ may be a candidate marker for success in motion sickness habituation Certain groups with medical conditions may be at 4. Predictors of individual differences in motion sickness elevated risk. Many patients with vestibular pathology and disease and vertigo can be especially sensitive to any type ofmotion. The well known association among migraine, Given a sufficiently provocative stimulus nearly all motion sickness sensitivity, and Meniere's disease dates people can be made motion sick. (This assumes of course back to the initial description of the syndrome by Prosper that the person has not been subjected to prior habituation or Meniere in 1861. It has been proposed that there may be a desensitisation to the stimulus or pre-medicated with high (genetic) link caused by defective calcium ion channels doses of anti-motion sickness drugs.) Indeed, almost the only shared by the brain and inner ear leading to reversible hair individuals who are immune to motion sickness are those cell depolarization, producing vestibular symptoms and that who have complete bilateral loss of labyrinthine (vestibular the headache might just be a secondary phenomenon ( apparatus) function. Even this may not be absolutely true An alternative explanation has been proposed based under all circumstances. There is evidence that bilateral upon different functioning of the serotonergic system in the labyrinthine defective individuals are still susceptible to motion sickness provoked by visual stimuli designed to Doubtless there is a genetic contribution to the individual induce self-vection during pseudo-Coriolis stimulation, i.e., differences in susceptibility, but the evidence is limited and pitching head movements within a moving visual field open to various interpretations. An example is the observa- (). It is also worth noting that blind or tion that a single-nucleotide polymorphism of the α2- blind-folded normally sighted individuals can be made adrenergic receptor increases autonomic responses to stressand contributes to individual differences in autonomic 1 The historical analogy is with the measurement and the factor analysis of ‘intelligence’ where it is now generally accepted that, depending on how However, it is unclear whether this is a marker for motion one wishes to regard the data, there exists a general intelligence quotient sickness susceptibility, per se, or a general marker for (IQ) factor, or just two oblique factors called verbal versus spatial and autonomic sensitivity. There is some evidence for Chinese numerous specific ability factors. As with IQ, for many practical purposes hyper-susceptibility to motion sickness, and this may the single general factor solution is the most useful for predicting anindividual's overall susceptibility.
provide some indirect evidence for a genetic contribution J.F. Golding / Autonomic Neuroscience: Basic and Clinical 129 (2006) 67–76 subsequent decline of susceptibility during the teenage years towards adulthood around 20 years. This doubtless Sex and age are two main predictors in the general reflects habituation. Although it is often stated that this population of individual susceptibility. Surveys of transpor- decline in susceptibility continues in a more gradual fashion tation by sea, land, and air, indicate that women are more throughout life towards old age, the evidence is weak given susceptible to motion sickness than men; women show that older people may avoid motion environments if they higher incidences of vomiting and reporting a higher know that they are susceptible. Indeed, longitudinal evidence from individuals who have been studied objectively in the This increased susceptibility is likely to be objective laboratory suggests that towards older age, susceptibility and not subjective because women vomit more than men.
may increase in some individuals (personal communication, For example, large scale surveys of passengers at sea indicate Michael Gresty, Medical School Imperial College, London, a 5 to 3 female to male risk ratio for vomiting ). It does not seem related to extra habituation to A multiplicity of other possible predictors of suscept- greater ranges of motion environments experienced by risk- ibility have been examined over the years, with relatively few being found to be of significance. Cross-sectional differential self-selection between males and females when surveys show that individuals with high levels of aerobic volunteering for laboratory motion sickness experiments fitness appear to be more susceptible to motion sickness, and experiments show aerobic fitness training increases exclusive to humans because in animals, such as Suncus motion sickness susceptibility (e.g., ).
murinus, females show significantly more emetic episodes The reasons are unclear, with one suggestion being that a and shorter latencies to emesis in experimental exposures to more reactive autonomic nervous system (including hypothalamic–pituitary–adrenal axis) in aerobically fit motion sickness susceptibility in women has been suggested individuals may sensitize them. Psychological variables to involve the female hormonal cycle. However, although such as mood may modify susceptibility in contradictory susceptibility probably does vary over the menstrual cycle, it directions: ‘state’ variables such as extreme fear or anxiety is unlikely that this can fully account for the greater conditioned to motion, may contribute indirectly to motion susceptibility in females because the magnitude of fluctua- sickness susceptibility, although by contrast, extreme tion in susceptibility across the cycle is only around one third arousal ‘fight–flight’ such as observed in warfare may of the overall difference between male and female suscept- Personality ‘trait’ variables such as extraversion or females to motion sickness or indeed to post-operative neuroticism do not strongly predict motion sickness nausea and vomiting or chemotherapy induced nausea and susceptibility, with only minor correlations being observed between extraversion or similar personality traits with evolutionary function. Thus, more sensitive sickness thresh- olds in females may serve to prevent exposure of the foetus A recent study using the ‘Big Five’ personality to harmful toxins during pregnancy, or subsequently through inventory revealed no significant correlations for any milk. This elevated susceptibility in females may be ‘hard- personality factor with motion sickness susceptibility in wired’ but capable of up-regulation albeit variably by hormonal influences during the menstrual cycle and even Infants and very young children are immune to motion sickness. However they have no difficulty vomiting. Motionsickness susceptibility begins from perhaps around 6 to Habituation offers the surest counter measure to motion sickness. Habituation is superior to anti-motion sickness are uncertain. Puberty begins later (around 10–12 years) than ). The most extensive habituation programmes, often the age 6–7 years for onset of motion sickness susceptibility.
denoted “motion sickness desensitisation,” are run by the This implies that sex hormonal changes per se are not a direct military, where anti-motion sickness medication is contra- explanation for the onset of motion sickness susceptibility.
indicated for pilots because of side-effects including Another possibility is that the perceptuo–motor map is still drowsiness and blurred vision. These programmes have highly plastic and not fully formed until around 7 years of age. Most models of motion sickness propose that this extremely time consuming, lasting many weeks. Critical perceptuo–motor map provides the ‘expected’ invariant features include: (a) the massing of stimuli (exposures at patterns for detecting possible sensory mismatches in the intervals greater than a week almost prevents habituation), relationships between vestibular, visual and kinaesthetic (b) use of graded stimuli to enable faster recoveries and inputs. Following the peak susceptibility, there is a more sessions to be scheduled, which may help avoid the J.F. Golding / Autonomic Neuroscience: Basic and Clinical 129 (2006) 67–76 opposite process of sensitization, and (c) maintenance of a rich meals may inhibit motion sickness () positive psychological attitude to therapy ( may be contrasted with a study which drew the opposite conclusion that any meal of high protein or dairy foods 3–6 h Anti-motion sickness drugs are of little use in this context, prior to flight should be avoided to reduce airsickness oxygen may be effective for reducing motion sickness in medication may speed habituation compared to placebo in patients during ambulance transport. By contrast, it does not the short term, in the longer term it is disadvantageous. This alleviate motion sickness in individuals who are otherwise is because when the anti-motion sickness medication is healthy. This apparent paradox is perhaps explained by the discontinued, the medicated group relapses and is worse off suggestion that supplemental oxygen may work by amelior- than those who were habituated under placebo.
ating a variety of internal states that sensitize for motion Habituation, itself, is often stimulus specific, producing the problem of lack of generalisation and transfer ofhabituation from one type of motion to another. Thus, to foster transfer, it is useful to use as wide a variety of provo-cative motions as possible (see ‘Laboratory’ stimuli).
Many of the drugs currently used against motion sickness The studies by underline the specificity of were identified during World War 2, and certainly most had habituation to different types of motion, with different anato- mical patterns of neuronal functional changes (presumably They may be divided into the categories: antimuscarinics reflecting learning) in the vestibulo–olivo–cerebellar net- (e.g., scopolamine), H1 anti-histamines (e.g., dimenhydri- work to different classes of provocative stimuli. Research nate), and sympathomimetics (e.g., amphetamine). However, continues to optimise habituation approaches these drugs, alone or in combination (e.g., scopolamine + dexamphetamine) are only partially effective. The other extends to habituation training to reduce motion sickness newer potent antiemetics, D2 dopamine receptor antagonists produced by short arm rotors intended to provide artificial and 5HT3 antagonists, used for side effects of chemotherapy, are not effective against motion sickness ( structures such as the amygdala as well as such areas as the probably because their sites of action may be at vagal nucleus tractus solitarius are thought to be important in afferent receptors or the brainstem chemoreceptor trigger processes of induction of and habituation to motion sickness zone, whereas anti-motion sickness drugs act elsewhere.
All anti-motion sickness drugs can produce unwanted More immediate and short-term behavioural counter side effects such as drowsiness, promethazine being a classic measures include reducing head movements, aligning the head and body with gravito-inertial force generally accepted that some drugs, such as transdermal scopolamine or the calcium channel antagonist cinnarizine, protective postures may be incompatible with task perfor- are significantly less sedating than others mance. It is usually better to be in control, i.e., to be the the consequent performance decrements may still not driver or pilot rather than a passenger ( be acceptable in challenging occupations such as piloting ). Obtaining a stable external horizon reference is helpful (). With regard to the latter, a direct view out of a car window reduced sickness but a real time ) preventing drug absorption. Consequently, oral video display of the view ahead failed to reduce sickness in administration must anticipate motion. Injection overcomes the various problems of slow absorption kinetics and gastric Controlled regular breathing has been shown to increase stasis or vomiting. Other routes such as transdermal also significantly motion tolerance to provocative motion, being offer advantages providing protection for up to 72 h with low approximately half as effective as standard anti-motion constant concentration levels in blood, consequently redu- sickness drugs yet rapid to implement and free of side cing side effects. Its slow onset time can be offset by effects. The mechanism by which controlled breathing has its simultaneous administration of oral scopolamine enabling effect is uncertain but may involve activation of the known inhibitory reflex between respiration and vomiting ( However, there may be variability in absorption via the transdermal route which alters effectiveness between acupressure to be effective against motion sickness ( individuals (). Buccal absorption is effective with scopolamine but an even faster route is nasal tally, modification of diet has been said to alter susceptibility (alkaline) pH buffered formulations to promote absorption, to motion sickness. Unfortunately, the evidence is contra- peak blood levels may be achieved in 9 min dictory; for example, a recent study suggesting that protein- ‘Chewing gum’ formulations offer the prospect of J.F. Golding / Autonomic Neuroscience: Basic and Clinical 129 (2006) 67–76 adequate motion sickness prophylaxis with reduced side effects compared to tablets, due to a more sustained release Investigations of ‘new’ anti-motion sickness drugs effective against motion sickness in animals, but published include re-examination of ‘old’ drugs such as phenytoin, as data on humans are lacking with the exception of one study well as the development of new agents such as Neurokinin-1 showing anti-motion sickness actions of the anti-migraine antagonists. Phenytoin has anti-motion sickness potential (), although its complex pharmacokinetics and observations of the present author suggest that Vasopressin side effects limit practicality. Betahistine has been proposed V1a receptor antagonists are not effective against motion to have anti-motion sickness properties but a number of sickness in man. A recent finding is that 3-hydroxypyridine studies ) indicate that its action is too derivatives appear to have anti-motion sickness effects weak to be effective for practical purposes. Chlorphenir- amine is an antihistamine synthesised many years ago which proven anti-motion sickness properties in humans is the has anti-motion sickness actions without major side effects selective muscarinic M3/m5 receptor antagonist zamifenacin, which has a side effect profile lower than for scopolamine medication has not been made. Cetirizine and fexofenadine antihistamines are ineffective against motion sickness, drug development since antimuscarinics are possibly the perhaps because of their failure to have sufficient central most effective and well proven of any class of anti-motion versus peripheral nervous system actions ( The anti-psychotic Droperidol is shown to haveuseful anti-motion sickness action and may merit further study (), but its practical valuemay be offset by side effects. Benzodiazepines and The types of stimuli which can provoke motion sickness barbiturates have long been known to have anti-motion and the nature of the sensory conflicts are now better sickness actions but their sedating actions preclude routine understood. Non-pharmacological countermeasures have been increasingly refined, including behavioural modifica- research comparing lorazepam with other anti-motion tions, autogenic techniques such as controlled breathing and desensitisation training. At a neurophysiological level, there such as dexamethasone attracted some interest as a potential has been much progress in defining the critical pathways in anti-motion sickness agents over fifteen years ago, but the central nervous system involved in motion sickness.
evidence for their value is indirect (A recent However there has been less progress in a number of other observation suggests the drug tamoxifen (used in breast areas. At the most general level, there is still no consensus as cancer treatment) may prevent motion sickness to the reason why motion sickness should occur, although an raising the possibility that pathways involving the evolutionary explanation in terms of a ‘toxin detector’ is the estrogens may be capable of modulating motion sickness.
most accepted. Equally the reasons for the great individual Although opioids often elicit emesis, they have been shown differences in motion sickness susceptibility are still only in animals to have broad antiemetic actions for motion poorly understood. They are probably multiple. The ability sickness, the balance of effect may reflect relative actions at to modify readily the time constant of the vestibular ‘velocity the chemoreceptor trigger zone and the nucleus tractus store’ has emerged as a potential candidate marker for solitarius, or their differential actions on mu and delta opioid rapidity of habituation. The role of genetics is doubtless receptors Work on the animal model S.
important but has received little attention as yet. Many of the murinus suggests that endogenous opioids may play a role in anti-emetics developed for other types of sickness such as in chemotherapy, have proved ineffective for motion sickness.
and one study has shown that the mu-opioid receptor agonist This suggests a divergence at some level in pathways loperamide affords some motion sickness protection in responding to emetic chemical versus motion stimuli. New humans (). It has been suggested that ginger anti-motion sickness drugs continue to be developed with the (main active agent gingerol) acts to calm gastrointestinal aim of producing greater efficacy with fewer side-effects.
feedback (), but studies of its effects on Selective anti-muscarinics, opioid antagonists and seroto- motion sickness have been equivocal making it an unlikely nergic agonists may be of promise. The development of new pharmacological countermeasures and a greater knowledge The new neurokinin NK1 receptor antagonists are potent of possible genetic factors will feedback into our under- broadband antiemetics. They are highly effective against standing of the neural mechanisms of motion sickness.
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