improve accommodation as evidenced by its prevention of hyoscine-induced impairment of accommodation (Alhalel et al., 1995).

Borland et al. (1985) described PB-induced improvement in the threshold for the fusion of flickering light and augmentation of dynamic visual acuity, findings the authors attributed to stimulation of CNS cholinergic actions. If these findings were related to CNS action, it would argue against the more generally accepted idea that PB cannot significantly penetrate the blood–brain barrier (see earlier discussion). These findings are important for the issue of possible long-term PB effects but currently are preliminary and unconfirmed. Other authors conclude that any observed effects on visual function are due to the peripheral action of PB on the pupillary sphincter, ciliary muscle, or oculomotor muscles. In general, the visual function effects of PB at routine CW pre-exposure doses are mild and reversible. However, the possibility of long-term or latent effects is difficult to assess since the studies reviewed were all of short duration.

Gastrointestinal Effects in Healthy Volunteers

Oigaard (1975) examined and compared the effects of PB and metoclopramide on upper gastrointestinal activity in 40 normal volunteers and 8 postoperative laparotomy patients. Using simultaneous recordings of electrical action potentials and intraluminal pressure, investigators compared the effects of the two drugs on upper gastrointestinal activity in healthy and surgical subjects. Measurements were taken after an oral dose of 40 mg of metoclopramide or an intravenous dose of 1.5 mg of PB. Both drugs had significant excitatory effects, with metoclopramide being the stronger stimulant of gut activity (possibly because the experimental dose of PB was relatively less potent than that chosen for metoclopramide).

A 1967 report of pharmacologic regulation of salivary gland secretion assessed PB’s effects on the saliva flow rate (Mandel et al., 1967). Both neostigmine and PB increased salivary flow, PB to a lesser degree than neostigmine.

In conclusion, studies of PB administration to normal volunteers demonstrate its expected short-term stimulatory effects on gastrointestinal motility and salivation, without any noted adverse effects.

Overall Performance in Healthy Volunteers

A number of studies have been carried out to assess overall measurements of both physiological and behavioral or cognitive parameters in healthy subjects treated with PB.

Izraeli and colleagues (1990) examined the effect of four doses of PB (30 mg every 8 hours) on flight skills in a placebo-controlled, double-blind, crossover study. The technical performance of 10 healthy male pilots (21–33 years) was tested in a flight simulator. No decrement in flight performance was observed among subjects treated with PB compared to placebo. Although they were mild in quality, slightly more symptoms were noted in PB-treated subjects.



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