Effects of acute doses of oxiracetam in the scopolamine model of human amnesia

Abstract

The scopolamine model of amnesia has been used to test the pharmacodynamic efficacy of oxiracetam in 12 healthy volunteers. The subjects were divided into four experimental groups, according to a double-blind cross over incomplete randomized block design. After a baseline neuropsychological examination, each subject received in two separate sessions one of the following treatments, as acute oral doses: oxiracetam 800, 1600, 2400 mg or placebo. One hour after treatment scopolamine hydrobromide (0.5 mg) was given subcutaneously. The cognitive performance was tested before and 1, 2, 3 and 25 h after scopolamine administration. Scopolamine caused a deterioration of performance of verbal episodic memory, semantic memory and attention tests. In comparison to placebo, oxiracetam improved the overall test performance, with a statistically significant difference at the dose of 1600 mg on delayed recall of word lists, and showed dose-related antagonism of scopolamine-induced effects also on semantic memory and attention. The efficacy of an acute dose of oxiracetam in reducing scopolamine-induced cognitive impairment supports the potential usefulness of this pharmacological model of amnesia for studying the effects of cognition enhancers in humans.

Pharmacokinetic–pharmacodynamic relationships of central nervous system effects of scopolamine in healthy subjects

“…Scopolamine affected most of the measured PD parameters of this study. Most effects were reasonably consistent with the effects described in the literature [5,18,23,26,27,46,48] and disappeared within 8 h. Some of the more noticable PD results will be briefly discussed below.…”

“…As cholinergic systems play an important role in memory processing, scopolamine has been applied as a disease model for dementia [10] and working memory impairment in schizophrenia [15]. The challenge test has been used to show the pharmacological activity of putative cognition enhancers by reversal of scopolamineinduced cognitive and other CNS deficits in healthy volunteers, including cholinergic drugs [16,17], oxiracetam [18] and D-cycloserine [19].…”

Caffeine attenuates scopolamine-induced memory impairment in humans

“…Since different studies use different word lists with different lengths and different amounts of presentation trims, some difficulties may arise as to the comparison of absolute values of treatment effects. As can be con-cluded from the results shown in Table 7, the absolute attenuation scores of the scopolamine-induced deficits in word recall obtained in our study after caffeine and nicotine are indeed small, but do not deviate drastically from (significant) results obtained in other studies with putative cognitive enhancers such as the neuropeptide TRH (Molchan et al t990), and the nootropic substances aniracetam (Wesnes et al 1990), and oxiracetam (Preda et al 1993).…”

No synergistic effect of subtherapeutic doses of donepezil and EVP‐6124 in healthy elderly subjects in a scopolamine challenge model

“…Although other studies showed a decrease of cognitive impairment due to the combination of donepezil and EVP‐6124 without use of the scopolamine challenge model, it remains under debate whether the challenge model was suitable to show the expected synergy in this study. The scopolamine challenge test has been successfully used in drug development to demonstrate the pharmacological activity of cognition‐enhancing compounds by reversal of scopolamine‐induced cognitive deficits in healthy volunteers [15,42–48]. Evidence also suggests that low concentrations of scopolamine (0.3 mg subcutaneous) can already induce a measurable significant decline in visuomotor speed and spatial working memory in healthy older people [15].…”