Nicergoline in dementia - A review of its pharmacological properties and therapeutic potential

Nicergoline is a semisynthetic ergoline derivative indicated for the treatm ent of cognitive impairment in various forms of dementia. It is currently a vailable for use in Italy and some other European countries, in Latin Ameri ca and the Near and Far East. In animal studies nicergoline exhibits a broad spectrum of actions on cellu lar and molecular mechanisms involved in the pathophysiology of dementia. N icergoline appears to enhance cholinergic and catecholaminergic neurotransm itter function and improve related cognitive deficits; stimulate phosphoino sitide turnover: modulate protein kinase C (PKC) translocation and PKC-medi ated alpha -secretase processing of amyloid precursor protein; increase reg ional cerebral blood flow and glucose uptake and utilisation; activate prot ein synthesis; protect neurons from death induced by oxidative stress or ap optosis; and interact with endogenous nerve growth factor-mediated processe s providing trophic support to cholinergic neurons. Whether these actions a re interrelated or represent multiple, unrelated effects is still unknown, but all may be relevant to the therapeutical use of the drug. Recent double-blind, placebo-controlled, randomised clinical studies of up to 12 months' duration indicated a measurable effect of nicergoline on cogn itive performance in patients with dementing illnesses. Medium and long ter m treatment resulted in significantly greater cognitive improvement or less decline than placebo as measured by Mini-Mental State Examination (MMSE) o r Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog) scor es. While deterioration represents the natural course of the disease, nicer goline-treated patients improved or maintained their previous clinical stat us. The objective improvement of the cognitive symptoms was paralleled by a stabilised or improved clinical global condition as evaluated by clinician s, caregivers and patients. Nicergoline was well tolerated in all clinical studies. The type, frequency and severity of adverse events were generally comparable with those observ ed in the placebo control groups. No clinically or statistically significan t changes in vital signs and laboratory evaluations were reported, except f or an asymptomatic increase of serum uric acid levels. Overall, data strongly support the hypothesis that nicergoline might interf ere with fundamental molecular mechanisms underlying cognitive processes ir ? vivo. The clinical results also indicate that nicergoline is a well toler ated and effective treatment that improves cognitive and global functions i n patients with mild to moderate dementia.