A Study to Assess The Anticholinergic Activity of Rolipram in Healthy Elderly Volunteers

Abstract

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.

Transdermal drug delivery treatment for overactive bladder

“…Saliva output has been shown in previous studies to be a valid surrogate marker of dry mouth (31,32). Saliva output was greater in patients receiving transdermal therapy when compared to extended release oral therapy.…”

Absence of Anticholinergic Activity of Rolipram, an Antidepressant with a Novel Mechanism of Action, in three Different Animal Models in Vivo

“…In contrast to the tricyclic antidepressants, rolipram and its enantiomers showed no anticholinergic activity at dosages up to 250 to 500 times higher than those required to exert antidepressant action in mice (Przegalinski and Bigajska, 1983;Wachtel, 1983 b). The absence of anticholinergic properties in rolipram, in contrast to amitriptyline, has recently been shown in healthy elderly volunterers by measuring saliva production after a single or repeated intake of the antidepressants (Ross et al, 1988). It is generally believed that the antimuscarinic properties of antidepressants reflect their propensity to cause peripheral and central adverse efTects.…”

Rolipram versus nortriptyline in gerontopsychiatric inpatients with major depression

“…Rolipram has no monoamine oxidase inhibitory activity and does not inhibit reuptake of monoamines into the presynaptic neuron (4). It is also devoid of anticholinergic effects (5,6). The potential usefulness of rolipram was suggested on the basis of its pronounced efficacy in classic animal tests predictive of antidepressant action (1)(2)(3).…”