Comparison of central and peripheral pharmacologic effects of biperiden and trihexyphenidyl in human volunteers.
In this double-blind, randomized study, indices of central (memory, sedation) and peripheral (salivation, ratio of R-R interval on electrocardiogram) muscarinic function were evaluated in 14 healthy volunteers who received trihexyphenidyl, biperiden, and placebo. Additionally, serum drug levels were obtained 2 hours after oral administration. All subjects participated in three study sessions. During each session, subjects received two doses of biperiden (4 mg), trihexyphenidyl (5 mg), or placebo, and four series of tests were administered. The tests included the determination of cardiac response to standing (R-R ratio), mouth salivation, finger-tapping speed, digit span (forward and backward), a selective reminding task, and visual analog scales (VAS). On the VAS, subjects rated biperiden as significantly more sedating than either trihexyphenidyl or placebo, and both biperiden and trihexyphenidyl were associated with more dizziness than was placebo. Saliva production was significantly reduced by both trihexyphenidyl and biperiden compared with placebo. Digit span performance was significantly decreased in only the backward direction. The selective reminding task revealed highly significant decrements in the number of words recalled and consistent long-term retrieval after both biperiden and trihexyphenidyl. Delayed recall was significantly decreased by both active drugs. Both trihexyphenidyl and biperiden caused a significant increase in the R-R ratio comparison with placebo. With the exception of the VAS measurement of sedation, the effects caused by biperiden and trihexyphenidyl did not differ. The results of this study do not support the hypothesis that the side effect profile of biperiden is significantly different from that of trihexyphenidyl.
Guthrie
S K
SK
College of Pharmacy and Department of Psychiatry, The University of Michigan, Ann Arbor 48109-1065, USA. salgut@umich.edu
Manzey
L
L
Scott
D
D
Giordani
B
B
Tandon
R
R
D000293:Adolescent; D000328:Adult; D001712:Biperiden / Q000097:blood / Q000494:pharmacology*; D004311:Double-Blind Method; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D011939:Mental Recall / Q000187:drug effects*; D018727:Muscarinic Antagonists / Q000097:blood / Q000494:pharmacology*; D010919:Placebos; D011597:Psychomotor Performance / Q000187:drug effects; D012472:Salivation / Q000187:drug effects; D014282:Trihexyphenidyl / Q000097:blood / Q000494:pharmacology*
D018727:Muscarinic Antagonists; D010919:Placebos; D001712:Biperiden; D014282:Trihexyphenidyl