Enhanced anti-amnestic effect of donepezil by Ginkgo biloba extract (EGb 761) via further improvement in pro-cholinergic and antioxidative activities.

ETHNOPHARMACOLOGICAL RELEVANCE: EGb 761 is a standardized dry extract of Ginkgo biloba L. leaves traditionally used by Eastern Asia and has been associated with beneficial effects on neurodegeneration disorders, including Alzheimer's disease. AIM OF THE STUDY: Since beneficial interactions between EGb 761 and donepezil have been observed in previous clinical studies, the current study was proposed aiming to further explore related mechanisms from both pharmacokinetics and pharmacodynamics aspects. MATERIALS AND METHODS: Pharmacodynamic interactions were studied in scopolamine-induced cognitive impairment rats received two-weeks treatment of vehicle, EGb 761 and/or donepezil by the Morris water maze test and ex vivo evaluation of biomarkers of cholinergic transmission and oxidative stress in rat brain. In the meantime, pharmacokinetic profiles of donepezil and bilobalide were obtained and compared among all treatment groups. In addition, impact of the bioavailable EGb 761 components on donepezil brain penetration was evaluated with the hCMEC/D3 cell monolayer model. RESULTS: Scopolamine-induced rats with co-treatment of EGb 761 and donepezil had significantly improved cognitive function in the Morris water maze test with increased brain levels of superoxide dismutase and decreased brain levels of acetylcholinesterase and malondialdehyde than that with treatment of only EGb 761 or donepezil. Despite such beneficial pharmacodynamics outcomes, the two-week co-treatment of EGb 761 and donepezil did not alter the plasma pharmacokinetics and brain uptake of donepezil or bilobalide, which was further verified in the hCMEC/D3 monolayer model. CONCLUSION: Co-administration of EGb 761 and donepezil exerted better anti-amnestic effect via further enhanced pro-cholinergic and antioxidative effects of EGb 761 or donepezil in scopolamine-induced cognitive impairment rat without alteration in their systemic/brain exposure.

Acute effect of nicotine on non-smokers: II. MLRs and 40-Hz responses.

This paper is the second in a series of three investigating the role of cholinergic mechanisms in the auditory system by assessing the acute effects of nicotine, an acetylcholinomimetic drug, on aggregate responses within the auditory pathway. In a single-blind procedure, auditory responses were obtained from 20 normal-hearing, non-smokers (10 male) under two conditions (nicotine, placebo). The effects of nicotine on central, mesogenous responses of the auditory system (middle latency and 40-Hz responses) are described in this second paper. Results indicated that transdermal administration of nicotine to non-smokers does significantly affect the central, neural transmission of acoustic information. Na-Pa amplitude and Nb latency of the middle latency response and latency measures of the 40-Hz response were acutely altered by the presence of nicotine.

Acute effect of nicotine on non-smokers: III. LLRs and EEGs.

This paper is the last in a series of three investigating the role of cholinergic mechanisms in the auditory system by assessing the acute effects of nicotine, an acetylcholinomimetic drug, on aggregate responses within the auditory pathway. In a single-blind procedure, auditory responses were obtained from 20 normal-hearing, non-smokers (10 male) under two conditions (nicotine, placebo). The effects of nicotine on long-latency responses of the auditory system and on electroencephalograms are described in this paper. Results indicated that transdermal administration of nicotine to non-smokers significantly affects the afferent and efferent transmission of acoustic information, as well as enhancing cortical activation. Long-latency response amplitudes and electroencephalogram activity (dominant power and frequencies) were altered by acute doses of transdermal nicotine.