Rl. Kohl et al., FACILITATION OF ADAPTATION AND ACUTE TOLERANCE TO STRESSFUL SENSORY INPUT BY DOXEPIN AND SCOPOLAMINE PLUS AMPHETAMINE, Journal of clinical pharmacology, 33(11), 1993, pp. 1092-1103
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.