VIEWS & REVIEWS
Ben~tS :With niCotine in cognitive disorders - not just a pipe dream ~ . "-.
-Sean Henahan-
Researchers 8ft dearing the smokescreen surrounding nicotine use in nenropsychiatric disorders. Recent findings indieate that nkotine JPay have beneficial effects in controlling the symptoms of Tourette's syndrome and may improve cognitive function in Alzheimer's disease. However, researchers remain unconvinced about the feasibility of using nicotine in treating schizophrenia. These findings, and the potential for using nicotinic agonists in cognitive disorders, were discussed at the inaugural conference of the Society for Resean:h on Nicotine and Tobacco [San Diego, US,' March 1995].
'Although the health risks associated with its {nicotine] intake via tobacco products have tended to tarnish society s view of nicotine. it is important to recognise that nicotine may have therapeutic potential in several disease states', commented Dr Ovid Pomerleau, President of the Society for Research on Nicotine and Tobacco, University of Michigan, US.
Initial investigations into the effects of nicotinic agents have confirmed the importance of the integrity of the nicotinic cholinergic system for normal cognitive functioning, according to Dr Pomerleau.
Swearing that nicotine works in 'Iburea2's syndrome
Dr Paul Sanberg, University of South Florida. US. presented preliminary data suggesting that very low doses of nicotine could have dramatic effects in controlling the symptoms of Tourette's syndrome.
He reviewed a series of patients in whom control of coprolalia, tics and other symptoms was achieved following the use of a single 7mg nicotine patch, with or without concurrent antipsychotic [neuroleptic] therapy. Interestingly, the patients with the most severe symptoms appeared to gain the most benefit from this treatment.·
'Most patients with Toureltes syndrome are treated with a neuroleptic agent and generally respond weJJ to this approach'. said Dr Sanberg. 'But there are a number of patients that are not as responsive to neuroleptics and need some further help. Our studies suggest that these patients may be helped by nicotine therapy'.
According to Dr Sanberg, a double-blind study investigating the effects of daily use of nicotine patches is DOW underway.
Putfs of smoke in schizophrenia Other investigations have provided new data
showing that nicotine intake, in the form of tobacco smoking, transiently normalised some of the psychophysiological deficits seen in patients with schizophrenia, reported Dr Robert Freedman from the University of Colorado, US. 'This may explain the high prevalence of smoking among patients with schizophrenia, and could lead to the development of novel therapeutic approaches', he suggested. Dr Freedman also noted that a higher percentage of both male and female patients with schizophrenia are
• Set also InphanM 897: 14, 24 Juil993; lKX1208164 und Inpharmo. 967: 14, 10D« 1994; 800325514
.. Set 1npharma944: 9--10, 2 Jui 1994; W1272006
heavy smokers and smoke the higher tar brands, compared with the general population.
Having observed that patients with schizophrenia are extremely sensitive to sensory stimuli. Dr Freedman conducted a series of electrophysiological studies involving auditory-evoked potentials. These studies revealed that healthy volunteers can inhibit the EEG response to repeated tones whereas patients with schizophrenia cannot. Further studies led Dr Freedman to conclude that nicotinic receptors were involved in this phenomenon.
Chewing it over- nicotine gwn oonnaJioies the EEGrespome
Dr Freedman then studied the effects of nicotine gum in relatives of patients with schizophrenia; these individuals were free from mental illness. but lacked the inhibitory response to repeated tones. After chewing nicotine gum, the EEG response in these volunteers was normalised.
Furthermore, a subsequent study in patients with schizophrenia (who were cigarette smokers) revealed that cigarette smoking produced a short-term normalisation of the EEG abnonnality.
'Nicotine per se does not appear to offer a useful approach to treating schizophrenia because of its short-term effects and the high risk of adverse effects', commented Dr Freedman. However, the research does offer new targets for drug development, and some encouraging work is already underway. 'It may be that schizophrenia is the wrong disease to treat with nicOline', he added, also noting that other forms of psychosis, particularly manic and senile disorders, have different responses to cholinergic agents.
Nicotine in Alzheimer's- a burning moe There is an increasing amount of clinical data
supporting a potential role for nicotine in the treatment of Alzheimer's disease," according to Dr Paul Newhouse, University of Vermont College of Medicine. US.
Alzheimer's disease is characterised by a loss of cholinergic neurons in the basal forebrain, with an associated loss of nicotinic receptors. This group of cells is critical for the regulation of cerebral blood flow and for cognitive performance.
Clinical studies have shown that IV administration of nicotine to nonsmoking patients with Alzheimer's disease, produces significant improvements in longterm recall and attention span. However, increases in symptoms of anxiety and depression are also seen.
'We can demonstrate that Joss of nicotinic receptors has junctional consequences for cognitive processes and that nicotinic agonists can provide
3
4 VIEWS & REVIEWS
Nicotine - continued
improvements', said Dr Newhouse. This suggests that nicotinic agonists might have benefits in Alzheimer's disease or in other forms of dementia where nicotinic receptor loss has been observed.
'Where Alzheimer's disease is concerned, a small effect on cognitive junction is a positive step. No one pretends that nicotinic agonists are likely to produce a cure for this disease. but I think they mQy form parI of a therapeutic package', believes Dr Newhouse. Several studies in patients with Alzheimer's disease are now investigating the efficacy of the nicotine patch approach. In addition, other researchers are attempting to develop new nicotinic agonists targeted at specific nicotinic receptor SUbtypes, with the aim of achieving the beneficial effects seen with nicotine, but without the adverse effects.
0156-2703195/t)984.00041$01 .00"' MI. Inter..-1onIo1 Umllecllee5. All rittrt. rnerwcl
