Bioavailability of intranasal promethazine dosage forms in dogs.

Ramanathan R, Geary RS, Bourne DW, Putcha L.

KRUG Life Sciences Inc., Houston, TX, USA.

Intramuscular promethazine (PMZ) is used aboard the US Space Shuttle to ameliorate symptoms of space motion sickness. Bioavailability after an oral dose of PMZ during space flight is thought to be impaired because of gastrointestinal disturbances associated with weightlessness and space motion sickness. In an attempt to find an alternative dosage form for use in space, we evaluated two intranasal (i.n.) dosage forms of PMZ in dogs for absorption and bioavailability relative to that of an equivalent intramuscular dose. Promethazine (5 mg kg-1) was administered as two intranasal dosage forms and as an intramuscular (i.m.) dose to three dogs in a randomised cross-over design. Serial blood samples were taken and analysed for PMZ concentrations and the absorption and bioavailability of PMZ were calculated for the three dosage forms. PMZ absorption from the carboxymethyl cellulose microsphere i.n. dosage form was more rapid and complete than from the myverol cubic gel formulation or from an i.m. injection. Bioavailability of the microsphere formulation was also greater than that of the gel formulation (AUC 3009 vs 1727 ng h ml-1). The bioavailability of the two i.n. dosage forms (relative to that of the i.m. injection) were 94% (microsphere) and 54% (gel). The i.n. microsphere formulation of PMZ offers great promise as an effective non-invasive alternative for treating space motion sickness due to its rapid absorption and bioavailability equivalent to the i.m. dose.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9697152&dopt=Abstract motion sickness




Optokinetic nystagmus correlates with severity of vection-induced motion sickness and gastric tachyarrhythmia.

Hu S, Stern RM.

Department of Psychology, Humboldt State University, Arcata, CA 95521, USA.

PURPOSE: The present study investigated the relationship of the frequency of nystagmus to the severity of optokinetic rotation-induced motion sickness. METHODS AND RESULTS: Eighty-seven subjects viewed a vertically striped, rotating drum for 16 min. Subjects' electrooculograms, ratings of vection, and subjective symptoms of motion sickness (SSMS) were measured during the drum rotation period. Subjects' electrogastrograms (EGGs) were recorded throughout the baseline and drum rotation periods. The ratios of the spectral intensity of EGG 4-9 cycles per minute (cpm) between drum rotation and baseline periods were calculated. The results indicated that the frequency of nystagmus was positively correlated with the ratings of vection (r = 0.40, p < 0.0001), scores of SSMS (r = 0.61, p < 0.0001), and ratios of EGG 4-9 cpm spectral intensity between drum rotation and baseline periods (r = 0.54, p < 0.0001). CONCLUSION: These results demonstrated that more rapid eye movement indexed by higher frequency of optokinetic nystagmus are related to the development of symptoms of motion sickness and gastric tachyarrhythmia.

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Neuroendocrine and gastric myoelectrical responses to illusory self-motion in humans.

Koch KL, Stern RM, Vasey MW, Seaton JF, Demers LM, Harrison TS.

Department of Medicine, Pennsylvania State University, Hershey 17033.

We compared gastric myoelectrical activity and endogenous neuroendocrine responses in subjects with and without motion sickness elicited by illusory self-motion or vection. Rotating a drum with black and white vertical stripes around seated stationary subjects (n = 22) produced vection. Gastric myoelectrical activity was recorded with cutaneous electrodes. Thirteen subjects developed gastric dysrhythmias [4- to 9-cycles/min (cpm) signals] and motion sickness during vection, whereas nine subjects maintained normal 3-cpm gastric rhythms and remained symptom free. Base-line plasma cortisol and beta-endorphin levels were significantly greater (P less than 0.01) in the subjects who would develop gastric dysrhythmias and nausea compared with the subjects who would not develop motion sickness. Norepinephrine levels increased in the nauseated group immediately after vection ceased (354.6 +/- 41.1 pg/ml) compared with the symptom-free subjects (223.1 +/- 22.8 pg/ml, P less than 0.05). Epinephrine increased significantly (P less than 0.05) after vection only in the nauseated subjects, whereas dopamine levels were not altered by vection in either group. We conclude that 1) anticipatory increases in plasma cortisol and beta-endorphin occurred in subjects who would develop nausea and gastric tachyarrhythmias during vection; 2) endogenous epinephrine and norepinephrine were increased in subjects who had vection-induced nausea and gastric dysrhythmias; and 3) vection stimulates brain-gut interactions, resulting in gastric tachyarrhythmias and complex neuroendocrine responses in subjects with motion sickness.

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Motion sickness susceptibility and aerobic fitness: a longitudinal study.

Cheung BS, Money KE, Jacobs I.

Defence and Civil Institute of Environmental Medicine, Downsview, Ont., Canada.

A longitudinal study evaluated the susceptibility to motion sickness in initially unfit subjects before and after an endurance training program. Motion stimulation was provided by the Precision Angular Mover, in which the subject was tumbled head over heels about an Earth-horizontal axis at 20 cycles per minute in darkness. Maximal aerobic power and the blood lactate response to submaximal exercise were evaluated with cycle ergometry. The training program caused significant improvements in VO2max and endurance capacity, and a significant decrease in percent body fat. There was a significant (p less than 0.0125) increase in motion sickness susceptibility after the physical training, suggesting that increased physical fitness caused increased susceptibility to motion sickness in some individuals.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2156490&dopt=Abstract motion sickness




Vection and simulator sickness.

Hettinger LJ, Berbaum KS, Kennedy RS, Dunlap WP, Nolan MD.

Essex Corporation.

Simulator sickness has been identified as a form of motion sickness in which users of simulators exhibit symptoms characteristic of true motion sickness. In a fixed-base simulator, visual and vestibular sources of information specifying dynamic orientation are in conflict to the extent that the optical flow pattern viewed by the pilot creates a compelling illusion of self-motion, which is not corroborated by the inertial forces transmitted through the vestibular sense organs. Visually induced illusory self-motion is known as vection, and a strict interpretation of sensory conflict theory of motion sickness suggests that vection in a fixed-base simulator would be a necessary precondition for simulator sickness. Direct confirmation of this relation is reported in this article.

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Comparison of various motion stimuli on motion sickness and acquisition of adaptation in Suncus Murinus.

Kaji T, Saito H, Ueno S, Matsuki N.

Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.

Effects of various types of motion stimuli were compared to investigate optimum method to elicit motion sickness and adaptation in Suncus murinus (suncus). Three different direction of shaking in the horizontal plane, back and forth, right and left and revolving, induced emetic response to the similar extent. However, vertical shaking was far less effective in inducing motion sickness. Mild and severe horizontal shaking (15 min per day) was continued for 14 days and emetic response to standard motion stimulus was compared before and after the training. The severe daily acceleration strongly depressed the susceptibility to motion stimulus. The mild acceleration which was not emetic stimulus in itself also remarkably attenuated the vomiting response to standard motion stimulus. These results indicate that 1) the emetic responsiveness of the suncus does not depend on the modes of shaking as long as the direction is in the horizontal plane, 2) the suncus is relatively refractory to the vertical linear acceleration and 3) the adaptation to motion stimulus does not develop on the latest peripheral steps of the vomiting reflex pathways.

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Conditioned taste aversion and motion sickness in cats and squirrel monkeys.

Fox RA, Corcoran M, Brizzee KR.

Department of Psychology, San Jose State University, CA 95192.

The relationship between vomiting and conditioned taste aversion was studied in intact cats and squirrel monkeys and in cats and squirrel monkeys in which the area postrema was ablated by thermal cautery. In cats conditioned 7-12 months after ablation of the area postrema, three successive treatments with xylazine failed to produce either vomiting or conditioned taste aversion to a novel fluid. Intact cats, however, vomited and formed a conditioned aversion. In squirrel monkeys conditioned 6 months after ablation of the area postrema, three treatments with lithium chloride failed to produce conditioned taste aversion. Intact monkeys did condition with these treatments. Neither intact nor ablated monkeys vomited or evidenced other signs of illness when injected with lithium chloride. When the same ablated cats and monkeys were exposed to a form of motion that produced vomiting prior to surgery, conditioned taste aversion was produced and some animals vomited. These findings confirm other studies indicating motion can produce vomiting in animals with the area postrema destroyed and demonstrate that motion-induced conditioned taste aversion can be produced after ablation of the area postrema. The utility of conditioned taste aversion as a measure of subemetic motion sickness is discussed by examining agreement and disagreement between identifications of motion sickness by conditioned taste aversion and vomiting. It is suggested that a convincing demonstration of the utility of conditioned taste aversion as a measure of nausea requires the identification of physiological correlates of nausea, and caution should be exercised when attempting to interpret conditioned taste aversion as a measure of nausea.

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[Characteristics of motion sickness during prolonged otolith stimulation in anti-orthostatic position]

[Article in Russian]

Matsnev EI, Iakovleva IIa, Serebrennikov MI, Gavrilin BK, Zakharova LN, Nichiporuk IA, Isupov VG, Markin AS.

Thirty healthy volunteers were tested for an extended period of time (up to 4 hours) on modified parallel swings during a head-down tilt (-8 degrees) study. The pattern of motion sickness that developed in this situation was evaluated in terms of physiological parameters (electrocardiography, rheoencephalography, arterial pressure, respiration rate electrooculography, etc.), hormonal status, fluid-electrolyte balance, sensory function. The test subjects developed a vestibulo-hemodynamic syndrome that included vestibular disorders, spatial illusions, fluid displacement in the cranial direction, excitation of the hypothalamic-pituitary-adrenal system, changes in fluid-electrolyte balance. The resulting data may help better understand mechanisms underlying motion sickness.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2316129&dopt=Abstract motion sickness