Physiological and performance effects of pyridostigmine bromide in healthy volunteers: a dose-response study.
BACKGROUND
Questions have been raised about the role pyridostigmine bromide (PB) plays in the etiology of Gulf War veterans' illnesses. There is a need to understand better the physiological and behavioral effects of this drug, particularly at the 30-mg/8-h regimen recommended by the US Military. OBJECTIVE. To perform a double-blind, cross-over, dose-response study of PB in 67 healthy, young volunteers (31 women, 36 men).


METHODS
Volunteers were initially trained on a standardized test battery. Supervised administration of placebo (PL) and PB (every 8 h/5 days) occurred in each of two dosing weeks, separated by a non-dosing week. One group received 30 mg PB and PL, and the other 60 mg PB and PL. In each dosing week, the battery was performed after the first pill and again when steady-state plasma PB levels were achieved.


RESULTS
PB was associated with an overall improvement in reaction time on tests of memory and attention, and with a reduction in RMS error on a tracking task. PB slowed heart rate and decreased the high frequency component of heart rate variability (HF HRV). Dose-response effects were found only for HF HRV, and RMS error. The extent of cholinesterase inhibition was directly related to the magnitude of the HF HRV decrease, and was predicted by the weight-normalized PB dose. Cholinesterase inhibition was not related to the extent or severity of reported drug side effects.


CONCLUSIONS
PB does not appear to have detrimental physiological or performance consequences at the recommended 30-mg dose, or at twice that dose, when evaluated under non-stressful laboratory conditions.
Cook
Mary R
MR
Midwest Research Institute, 425 Volker Boulevard, Kansas City, MO 64110, USA. mcg@planetkc.com
Graham
Charles
C
Sastre
Antonio
A
Gerkovich
Mary M
MM
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004569:Electroencephalography; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D008297:Male; D011729:Pyridostigmine Bromide / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood; D011930:Reaction Time / Q000187:drug effects; D013647:Task Performance and Analysis
D002800:Cholinesterase Inhibitors; D011729:Pyridostigmine Bromide