Evaluation of the effects of anti-motion sickness drugs on subjective sleepiness and cognitive performance of healthy males

This study aimed to investigate the clinical and cognitive side effects of baclofen (10 mg), meclizine (25 mg), dimenhydrinate (40 mg) plus cinnarizine (25 mg) and promethazine (25 mg) plus d-amphetamine (10 mg). The study had a double-blind, placebo controlled, repeated measures design and was conducted on healthy male volunteers. The psychomotor vigilance test, the Sternberg working memory task, the implicit memory test and the automated Operation Span (Ospan) task were performed. The Stanford, the Karolinska and the Epworth Sleepiness scale determined the degree of sleepiness. The Profile of Mood States (POMS) evaluated mood states and adverse effects were reported on a 22-item questionnaire. Letter recalls and time for solving mathematical problems, recorded during the Ospan task, were impaired by baclofen and dimenhydrinate-cinnarizine respectively, suggesting an influence of these drugs on the working memory. Significant side effects for baclofen were: sleepiness, tiredness, blurred vision, concentration problems and dizziness whereas for dimenhydrinate-cinnarizine only sleepiness and blurred vision were reported. Meclizine decreased the accuracy on the Sternberg working memory task and thus seemed to affect short-term memory. A reported side effect was increased sleepiness. Promethazine plus d-amphetamine did not affect any of the tested cognitive functions. However, many side effects such as sleepiness, dry mouth, dizziness, vertigo, confusion, insomnia and tremors were reported. The results show that meclizine and dimenhydrinate combined with cinnarizine were the two drugs with the most acceptable combination of side effects. </jats:p

Intranasal scopolamine affects the semicircular canals centrally and peripherally

Space motion sickness (SMS), a condition caused by an intravestibular conflict, remains an important obstacle that astronauts encounter during the first days in space. Promethazine is currently the standard treatment of SMS, but scopolamine is used by some astronauts to prevent SMS. However, the oral and transdermal routes of administration of scopolamine are known to have substantial drawbacks. Intranasal administration of scopolamine ensures a fast absorption and rapid onset of therapeutic effect, which might prove to be suitable for use during spaceflights. The aim of this study was to evaluate the effects of intranasally administered scopolamine (0.4 mg) on the semicircular canals (SCCs) and the otoliths. This double-blind, placebo-controlled study was performed on 19 healthy male subjects. The function of the horizontal SCC and the vestibulo-ocular reflex, as well as the saccular function and utricular function, were evaluated. Scopolamine turned out to affect mainly the SCCs centrally and peripherally but also the utricles to a lesser extent. Centrally, the most probable site of action is the medial vestibular nucleus, where the highest density of muscarinic receptors has been demonstrated and afferent fibers from the SCCs and utricles synapse. Furthermore, our results suggest the presence of muscarinic receptors in the peripheral vestibular system on which scopolamine has a suppressive effect. Given the depressant actions on the SCCs, it is suggested that the pharmacodynamic effect of scopolamine may be attributed to the obliteration of intravestibular conflict that arises during (S)MS.</jats:p

Restricted sedation and absence of cognitive impairments after administration of intranasal scopolamine

Introduction: Space motion sickness in astronauts during spaceflight causes significant discomfort, which might impede their functionality. Pharmacological treatment has been mainly restricted to promethazine. Transdermal and oral scopolamine have also been used in space; however, their use was reduced due to unpredictable effectiveness and side effects. Recently, intranasal scopolamine administration has gained much interest, since this route ensures fast and reliable absorption with a decreased incidence of undesirable side effects. The aim of this study was to evaluate the effect of intranasal scopolamine on cognitive performance and to determine its side effects. Methods: This double-blind, placebo controlled, repeated measures study evaluated vigilant attention, short-term memory, implicit memory and working memory. Side effects were reported on a 22-item questionnaire and sleepiness was assessed by the Karolinska, Stanford and Epworth Sleepiness Scales. Results: Scopolamine had no effect on cognitive function. Only the Karolinska score was significantly increased for scopolamine compared to placebo. Participants reported a dry mouth and dizziness after receiving scopolamine. Discussion: Results show that intranasal scopolamine did not impair cognitive performance. Intranasal scopolamine might be a good alternative to promethazine for the alleviation of space motion sickness, since the agent has minimal sedative effects and does not hamper cognitive performance. </jats:sec