Intranasal Scopolamine for Motion Sickness.

INTRODUCTION: Rapid onset, noninjection methods are required to provide "as needed" therapy for motion sickness. Intranasal scopolamine (IN SCOP) is attractive because it can be fast acting and work when gastric motility is slowed. Intranasal administration can provide a time to maximal concentration (Tmax) of drugs (e.g., naloxone and midazolam) of 30 min or less. We evaluated the efficacy, pharmacodynamics, and pharmacokinetics of IN SCOP in a placebo-controlled, randomized, double-blind, dose-ranging study, and compared pharmacokinetic outcomes against other published results.METHODS: There were 18 healthy adult volunteers (10 M, 8F) who received placebo, low dose (0.2 mg), and high dose (0.4 mg) IN SCOP intranasally using a pump device and a gel formulation. Participants rode in an off-vertical axis rotation (OVAR) chair 1.25 h after dose administration and completed neurocognitive tests to evaluate secondary drug impacts. Pharmacokinetics (PK) and pharmacodynamics (PD) were assessed in eight subjects. PK data were compared to results from previously published studies.RESULTS: Low and high dose IN SCOP increased chair time significantly compared to placebo. No significant sleepiness or cognitive impairment was seen, likely due to the small sample size. Tmax was long for both dosages (High dose 75.0 ± 49.4 min, Low dose 61.9 ± 37.1 min), compared to other intranasally administered drugs and some previous studies with IN SCOP. Average Tmax was not superior to previously published values for dose-matched (0.4-0.5 mg), orally-delivered SCOP.DISCUSSION: IN SCOP has potential as a rapid administration route for relieving MS symptoms, but more work is needed to identify optimal intranasal formulation and dispensing methods.KEYWORDS: Motion sickness, pharmacokinetics, scopolamine, intranasal administration.Stankovic AS, Alvarenga DL, Daniels VRC, Simmons RG, Buckey JC, Putcha L. Intranasal scopolamine for motion sickness. Aerosp Med Hum Perform. 2019; 90(11):917-924.

The effect of oxygen therapy on brain damage and cerebral pO(2) in transient focal cerebral ischemia in the rat.

We examined the effect of hyperbaric oxygen (HBO) and normobaric oxygen (NBO) on neurologic damage and brain oxygenation before and after focal cerebral ischemia in rats. A middle cerebral artery occlusion (MCAO)/reperfusion rat model was used. The rats were sacrificed 22 h after reperfusion, and the infarct volume was evaluated. In study A, HBO (2.0 ATA), NBO (100% oxygen) and normobaric air (NBA) were each administered for 60 min in five different rat groups. The sizes of the infarcts after HBO and NBO applied during ischemia were 8.8 +/- 2.8% and 22.8 +/- 3.7% respectively of the ipsilateral non-occluded hemisphere. The infarct size after HBO applied during ischemia was statistically smaller than for NBO and NBA exposure (p < 0.01). In study B, cerebral pO(2) was measured before and after MCAO and HBO exposure (2.0 ATA for 60 min) in six rats using electron paramagnetic resonance (EPR) oximetry. The pO(2) in the ischemic hemisphere fell markedly following ischemia, while the pO(2) in the contralateral hemisphere remained within the normal range. Measurements of the pO(2) performed minutes after HBO exposure did not show an increase in the ischemic or normal hemispheres. The mean relative infarct size was consistent with the changes observed in study A. These data confirm the neuroprotective effects of HBO in cerebral ischemia and indicate that in vivo EPR oximetry can be an effective method to monitor the cerebral oxygenation after oxygen therapy for ischemic stroke. The ability to measure the pO(2) in several sites provides important information that should help to optimize the design of hyperoxic therapies for stroke.

Chlorpheniramine and ephedrine in combination for motion sickness.

BACKGROUND: Chlorpheniramine is effective against motion sickness, but produces sedation. To reduce chlorpheniramine's sedating effect and increase its effectiveness, ephedrine was combined with chlorpheniramine to prevent motion sickness. METHODS: Chlorpheniramine (C) and chlorpheniramine plus ephedrine (Chlorphedra) were studied in a randomized, double blind, crossover trial. Eighteen normal subjects were randomized to six different orderings of placebo, C (12 mg) or Chlorphedra (12 mg C + 50 mg ephedrine). They ingested the medication 3.25 hours before off vertical axis rotation in a rotating chair. Cognitive testing with both objective and subjective tests was performed before drug ingestion, at peak drug effect and following rotation. RESULTS: Both C and Chlorphedra significantly increased chair time compared to placebo [6.6 to 10.3 minutes (C), 10.2 minutes (Chlorphedra), p<0.01]. Subjects reported significantly more sleepiness on the Karolinska sleepiness scale after taking C (3.3 placebo, 4.9 C (p<0.005)) but not with Chlorphedra (3.3 placebo, 3.1 Chlorphedra). Chlorphedra resulted in significantly higher reported alertness, clearheadedness and attentiveness compared to C. Deficits seen on objective tests with C were corrected with Chlorphedra. Subjects noted more side effects with Chlorphedra. CONCLUSION: Ephedrine does not increase the effectiveness of chlorpheniramine against motion sickness, but counteracts sedative and performance effects successfully.

Dual-frequency ultrasound for detecting and sizing bubbles.

ISS construction and Mars exploration require extensive extravehicular activity (EVA), exposing crewmembers to increased decompression sickness risk. Improved bubble detection technologies could help increase EVA efficiency and safety. Creare Inc. has developed a bubble detection and sizing instrument using dual-frequency ultrasound. The device emits "pump" and "image" signals at two frequencies. The low-frequency pump signal causes an appropriately-sized bubble to resonate. When the image frequency hits a resonating bubble, mixing signals are returned at the sum and difference of the two frequencies. To test the feasibility of transcutaneous intravascular detection, intravascular bubbles in anesthetized swine were produced using agitated saline and decompression stress. Ultrasonic transducers on the chest provided the two frequencies. Mixing signals were detected transthoracically in the right atrium using both methods. A histogram of estimated bubble sizes could be constructed. Bubbles can be detected and sized transthoracically in the right atrium using dual-frequency ultrasound.

Hearing and performance during a 70-h exposure to noise simulating the space station environment.

INTRODUCTION: Elevated hearing thresholds have been documented in some astronauts after long-term spaceflights although noise levels were lower than those normally associated with noise-induced hearing loss in ground-based operations. The present study was conducted to determine whether prolonged exposure (70 h) to levels (72 dBA) recorded on the International Space Station (ISS) service module would impact diverse measures of auditory function, as well as cognition and memory, motivation, and cardiovascular function. METHOD: Five mixed gender subgroups of five normal-hearing subjects, aged 20-50 yr, were sequestered for 70 h in an environment that modeled conditions on the ISS. They were assigned to one of three background conditions: quiet (n = 5), continuous noise from the ISS service module (n = 10), or continuous noise during the day only (n = 10). Subjects were tested repeatedly within and across days as individuals or pair mates. RESULTS: There were no negative effects of the noise on any of the outcome measures. Introduction of a delay or noise in a communication channel used in the assessment of speech communicability significantly affected the time taken for joint problem solving by partners. DISCUSSION: The results of this study were not consistent with the observation of hearing loss measured after spaceflights. Nor were changes evident in cognition, motivation, or cardiovascular function. Factors which might account for the discrepancy are discussed.