Stress, Pyridostigmine and the Blood Brain Barrier

Abstract

Pyridostigmine is a carbamate acetylcholinesterase (AChE) inhibitor that does not readily enter the brain. It is used clinically in the treatment of myastenia gravis (Tylor, 1990), and as part of the treatment against nerve agents poisoning. In the latter, pyridostigmine is used as a pre-treatment, effective only in combination with an immediate post exposure administration of anticholinergic drugs and an oxime reactivator. It was widely used during the Gulf war as a pre-treatment against possible chemical warfare attack (Keeler et al.,1991) and following continuous reports of long-term illness in Gulf war veterans, was suspected to contribute to the illness termed “the Gulf War syndrome” (Blanck et al.,1995, Haley et al.,1997a-c, The Iowa Persian Gulf study group, 1997, Nisenbaum et al.,2000). However, the syndrome includes symptoms attributed to central nervous system (CNS) dysfunction (e.g. impaired cognition, fatigue, sleep disturbance, confusion), which could not be easily explained by the effects of a compound that does not enter the CNS. The controversy around the “Gulf war syndrome” was further complicated by the suggestion that stress exposure (physical conditions, combat related anxiety, perceived threat from biological or chemical weapons) may account for most of the long-term effects reported by the veterans (David et al.,1997, Hyams et al,1996, Ismail et al.,1999, Nisenbaum et al.,2000, but see also Haley et al.,1997).