TY - JOUR
T1 - Facilitation of Adaptation and Acute Tolerance to Stressful Sensory Input by Doxepin and Scopolamine Plus Amphetamine
AU - Kohl, Randall Lee
AU - Sandoz, Gwenn R.
AU - Reschke, Millard F.
AU - Calkins, D. S.
AU - Richelson, Elliott
PY - 1993/11
Y1 - 1993/11
N2 - This work characterizes a new methodologic and pharmacologic approach to control terrestrial and space motion sickness (SMS). The experimental design allowed separate evaluation of drug action on susceptibility and adaptability, and used repeated measures to approximate the chronic stressful motion of microgravity. Daily exposure to cross‐coupled angular acceleration for 5 consecutive days demonstrated that the efficacy of doxepin and scopolamine plus amphetamine in the prevention of autonomic system dysfunction was not only apparent on the first test day (P < .01), but was also evident in the substantially enhanced resistance developed over the 5‐day test period (P < .01) as compared with placebo. This indicates that daily use of these medications does not diminish therapeutic efficacy (tolerance). The efficacy of doxepin was anticipated because it possesses pharmacologic properties similar to those of established anti‐motion sickness drugs. Comparable efficacy after doxepin loading for 4 hours, 3 days, or 21 days suggests a mechanism distinct from its antidepressant effects, possibly related to its potent antihistaminergic actions. Use of doxepin has operational significance to the National Aeronautics and Space Administration, in comparison with current preparations of scopolamine plus amphetamine, because of doxepin's minimal impact on cognitive performance, and most importantly, its favorable pharmacokinetic profile, particularly its long half‐life. 1993 American College of Clinical Pharmacology
AB - This work characterizes a new methodologic and pharmacologic approach to control terrestrial and space motion sickness (SMS). The experimental design allowed separate evaluation of drug action on susceptibility and adaptability, and used repeated measures to approximate the chronic stressful motion of microgravity. Daily exposure to cross‐coupled angular acceleration for 5 consecutive days demonstrated that the efficacy of doxepin and scopolamine plus amphetamine in the prevention of autonomic system dysfunction was not only apparent on the first test day (P < .01), but was also evident in the substantially enhanced resistance developed over the 5‐day test period (P < .01) as compared with placebo. This indicates that daily use of these medications does not diminish therapeutic efficacy (tolerance). The efficacy of doxepin was anticipated because it possesses pharmacologic properties similar to those of established anti‐motion sickness drugs. Comparable efficacy after doxepin loading for 4 hours, 3 days, or 21 days suggests a mechanism distinct from its antidepressant effects, possibly related to its potent antihistaminergic actions. Use of doxepin has operational significance to the National Aeronautics and Space Administration, in comparison with current preparations of scopolamine plus amphetamine, because of doxepin's minimal impact on cognitive performance, and most importantly, its favorable pharmacokinetic profile, particularly its long half‐life. 1993 American College of Clinical Pharmacology
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U2 - 10.1002/j.1552-4604.1993.tb01946.x
DO - 10.1002/j.1552-4604.1993.tb01946.x
M3 - Article
C2 - 8300892
AN - SCOPUS:0027144503
SN - 0091-2700
VL - 33
SP - 1092
EP - 1103
JO - The Journal of Clinical Pharmacology
JF - The Journal of Clinical Pharmacology
IS - 11
ER -