A study to assess the anticholinergic activity of rolipram in healthy elderly volunteers

Rolipram is an antidepressant with a novel mechanism of action: enhanced noradrenaline (first messenger) synthesis and release, and inhibition of cAMP (second messenger) breakdown. This study was aimed at objectively assessing potential anticholinergic effects of rolipram in healthy elderly volunteers by measurement of saliva production and pupil size. Eight male volunteers between 67 and 77 years of age first received in a randomized manner either a single dose of 50 mg amitriptyline or a placebo control. After a minimum washout period of seven days, they then received a multiple dosing regimen of a) 0.75 mg and b) 1.5 mg rolipram given every eight hours over a 5-day period with a two day washout between a) and b). Whereas no changes at all in pupil size could be observed, amitripyline significantly reduced salivary flow. Rolipram however had no effect on saliva production after either single or repeated administration of 0.75 or 1.5 mg. The results are discussed in connection with pharmacokinetic parameters obtained in the study.