Chelen, Kabrisky, Hatsell, Morales, Fix and Scott, Aviation, Space and Environmental Medicine (1990), 3418 tested the efficacy of phenytoin in a placebo-controlled, double-blind, crossover pilot study of acute Coriolis-induced motion sickness treatment/prevention. At least one week separated the placebo and phenytoin trials for each of seven subjects. A total dose of 15 mg/kg of PHT was administered orally in 5 or 6 equal doses at approximately 4-hour intervals over a 20-hr period prior to Coriolis stimulation. Four hours after the final dose of PHT or placebo, Coriolis motion stimulus was generated. For those subjects given phenytoin, there was a mean increase in tolerance to motion sickness from 4.87 min (S.D. = 5.55) to 46.87 min (S.D. = 32.6). This represents a greater than four-fold improvement in efficacy over any currently available single agent and is more than twice as effective as the scopolamine/dexadrine combination. In addition, there were none of the usual side effects of blurred vision, dizziness, dry mouth, or sedation.
3418. Chelen, W.E., Kabrisky, M., Hatsell, C., Morales, R., Fix, E., and Scott, M., Use of phenytoin in the prevention of motion sickness, Aviat. Space Environ. Med., 61: 1022-5, 1990.
Chelen, Kabrisky, Rogers and Morales, 61st Annual Scientific Meeting of the Aerospace Medical Association (1990), 3419 reported the results of a double-blind, placebo-controlled crossover study of oral phenytoin's ability to prevent the symptoms of motion sickness in 16 male subjects. Coriolis stimulation (through voluntary head motion) in a rotating chair was used to induce emesis. In 11 of 14 subjects with phenytoin serum levels above 11.4 µg/ml, a reduction in the symptoms of motion sickness and/or an increase in the time to development of symptoms was seen.
3419. Chelen, W.E., Kabrisky, M., Rogers, S., and Morales, R., Dose/Response of phenytoin in the therapy of motion sickness, Presented at the 61st Annual Scientific Meeting of the Aerospace Medical Association, A59 (Abstr 362), New Orleans, LA, 1990.
Karkishchenko and Dimitriado, Kosmicheskaya Biologiya i Aviakosmicheskaya Meditsina (1991), 3420 investigated whether antiepileptic drugs affecting the GABA-ergic system, when used in combination, would prevent motion sickness. Motion sickness was induced through rotation and vestibular stimulation in healthy male volunteers. In a double-blind procedure, a single dose of the drugs or placebo was given 1-1.5 hours before the experiment. The effects of the various drugs alone or in combination are reported. Phenytoin (300 mg) or valproic acid (450 mg) were associated with significant anti-motion sickness effects. These effects included longer tolerance of complex acceleration and faster reduction of symptoms of motion sickness. Phenytoin (300 mg) and calcium pantothenate (100 mg) combined had a strong anti-motion sickness effect and also accelerated attenuation of motion sickness symptoms. This combination, the authors found in their study of conditioned evoked potentials, did not decrease the amplitude of the evoked potentials, suggesting less detriment to associative mental processes.
3420. Karkishchenko, N.N. and Dimitriadi, N.A., Antiepileptic drugs in the combined medicinal prevention of motion sickness, Kosm. Biol. Aviakosm. Med. (Moscow), 25(1): 21-23, 1991.
Chelen, Ahmed, Kabrisky and Rogers, Aviation, Space, and Environmental Medicine (1993), 3421 had previously evaluated phenytoin as an efficacious anti-motion sickness therapy in more than 24 individuals. To be effective, anticonvulsant serum levels of phenytoin were required to be reached in a short time. The authors conducted a double-blind, placebo-controlled, crossover study of twenty-three healthy males to determine if the abbreviated dosing interval of PHT caused any untoward side effects that might adversely affect aerospace operations. Each subject was tested on a performance battery (Criterion Task Set) on two occasions while on either phenytoin treatment or placebo for subsequent statistical comparison. Phenytoin serum levels ranging 8.9 to 23.9 micro g/L. While subjects with the higher serum levels consistently reported subjective side effects, there was no statistically significant degradation of sensory, cognitive, or performance capabilities compared to placebo. The authors added that, in laboratory motion sickness trials, combining phenytoin with dextromethorphan lowered the dosage of phenytoin required to be effective against motion sickness and, at the same time, decreased the incidence of subjective side effects associated with the rapid administration of phenytoin.
3421. Chelen, W.E., Ahmed, N., Kabrisky, M., Rogers, S., Aviat. Space Environ. Med., 64(3Pt 1): 201-5, 1993.
Woodward, Knox, Myers, Chelen and Ferguson, Aviation, Space, and Environmental Medicine (1993), 3422 explain that seasickness is the most prevalent form of motion sickness and is an operational problem during Space Shuttle Solid-fueled Rocket Booster (SRB) retrieval. In light of the evidence that phenytoin can protect against motion sickness induced by Coriolis stress, the authors exposed SRB recovery personnel to off-vertical rotation and sea motion after phenytoin or placebo.
Phenytoin blood levels of at least 9 µg/ml were protective against motion sickness at sea. No change in susceptibility to nitrogen narcosis was seen in divers in chamber tests at 460 KPa. To further evaluate its safety, phenytoin was used during performance of critical and hazardous tasks during training and actual SRB recovery operations. The authors conclude that phenytoin is an effective operational countermeasure for motion sickness for selected SRB crewmembers.
3422. Woodward, D., Knox, G., Myers, J., Chelen, W.E., Ferguson, B., Aviat. Space Environ. Med., 64(5) : 363-6, 1993.
Knox, Woodward, Chelen, Ferguson and Johnson, Laryngoscope (1994), 3423 have conducted a series of studies to investigate the efficacy of phenytoin for motion sickness prophylaxis and to gain insight into PHT's mechanism of action. In this study, the authors tested twenty participants with electronystagmography, off-vertical rotation, sea travel, and parabolic flight after they received phenytoin or placebo. A loading dose of PHT (500 - 1200 mg) was given as four doses at 10 AM, 2 PM, 6 PM and 6 AM the next morning. Thereafter, a maintenance dose (100 - 200 mg) was given every 24 hrs to produce a blood level of 9 - 12 µg/ml. Phenytoin and placebo were administered in a double-blind crossover manner in the rotating chair, small boat and caloric tests. Electronystagmography showed significant decreases in the gain of vestibule-ocular reflex in participants receiving phenytoin. Few side effects were seen with drug levels in the 9 - 15 µg/ml range. The authors conclude that phenytoin is an effective motion sickness counter measure that may exert its effect through a combination of central nervous system and peripheral vestibular effects.
3423. Knox, G.W., Woodward, D., Chelen, W.E., Ferguson, R., Johnson, L., Laryngoscope, 104(8Pt 1): 935-9, 1994.
Stern, Uijtdehaage, Muth and Koch, Aviation, Space and Environmental Medicine (1994), 3424 tested the prophylactic effects of a single low dose of phenytoin on motion sickness. In this double-blind study, fasted male subjects who were susceptible to motion sickness were given either a 200-mg tablet of phenytoin (N = 19) or a placebo (N = 16). Electrogastrograms (EGG'S) were recorded predrug, postdrug (four hours after ingestion of drug), before drum rotation, and during drum rotation. During testing, subjects were exposed to an optokinetic drum that was stationary for 8 min and which then rotated at 10 rpm for 16 min. The results showed that the phenytoin subjects had a lower mean subjective symptom score than the placebo group (5.8 vs. 7.1), but the difference was not significant. However, six of sixteen placebo subjects requested early termination of drum rotation due to symptom severity, whereas only two of nineteen phenytoin subjects terminated testing prematurely (X2 = 3.89, p < 0.05). The phenytoin group showed no increase in gastric tachyarrhythmia, the pattern of gastric myoelectric activity that usually accompanies nausea during drum rotation, whereas tachyarrhythmia doubled for the placebo group. The authors conclude that a single low dose of phenytoin prevents the development of gastric tachyarrhythmia and decreases the intensity of motion sickness symptoms.
3424. Stern, R.M., Uijtdehaage, S.H., Muth, E.R., Koch, K.L., Aviat. Space Environ. Med., 65(6): 518-21, 1994.