FACILITATION OF ADAPTATION AND ACUTE TOLERANCE TO STRESSFUL SENSORY INPUT BY DOXEPIN AND SCOPOLAMINE PLUS AMPHETAMINE

This work characterizes a new methodologic and pharmacologic approach to control terrestrial and space motion sickness (SMS). The experiment al design allowed separate evaluation of drug action on susceptibility and adaptability, and used repeated measures to approximate the chron ic stressful motion of microgravity. Daily exposure to cross-coupled a ngular acceleration for 5 consecutive days demonstrated that the effic acy of doxepin and scopolamine plus amphetamine in the prevention of a utonomic system dysfunction was not only apparent on the first test da y (P < .01), but was also evident in the substantially enhanced resist ance developed over the 5-day test period (P < .01) as compared with p lacebo. This indicates that daily use of these medications does not di minish therapeutic efficacy (tolerance). The efficacy of doxepin was a nticipated because it possesses pharmacologic properties similar to th ose of established anti-motion sickness drugs. Comparable efficacy aft er doxepin loading for 4 hours, 3 days, or 21 days suggests a mechanis m distinct from its antidepressant effects, possibly related to its po tent antihistaminergic actions. Use of doxepin has operational signifi cance to the National Aeronautics and Space Administration, in compari son with current preparations of scopolamine plus amphetamine, because of doxepin's minimal impact on cognitive performance, and most import antly, its favorable pharmacokinetic profile, particularly its long ha lf-life.