Publisher Summary In the present clinical neuropsychopharmacology, drugs acting primarily on cholinergic mechanisms within the CNS are utilized to a limited extent. In 1992, seven tertiary anticholinergic drugs (atropine, benztropine, trihexyphenidyl, biperidene, metixene, procyclidine and orphenadrine) are approved for clinical use in Sweden, while no cholinomimetic agent with central action is marketed. Physostigmine might be used occasionally as an antidote in the treatment of intoxication with certain antidepressant drugs. During the past 10 years, a number of clinical trials have been performed, which aim to restore the effects of a postulated central cholinergic hypo function in dementia by means of high doses of the acetylcholine precursor choline, by acetylcholinesterase inhibitors and by cholinergic agonists. So far, the therapeutic results can be characterized as marginal and of uncertain clinical significance. Evidently, drugs interfering with central cholinergic mechanisms have no major role at present in the therapy of neuropsychiatric conditions, with the exception of some movement disorders. In recent years, radioligand binding in crude fractions from tissue homogenates or in cryosections of CNS tissue for autoradiography, and to some extent immunohistochemistry, has been applied for localization and quantization of muscarinic and nicotinic binding sites in the human CNS postmortem. Lately, receptor subpopulations have been identified by means of selective ligands. It is obvious that such studies do not address functional aspects but will deliver information to the giant project of human brain mapping. In these postmortem studies, commonly arranged as preclinical-clinical collaborative projects, a common design is to compare tissue from controls and from cases dying with a neurodegenerative disorder, such as Alzheimer's disease (AD), Parkinson's disease, or amyotrophic lateral sclerosis (ALS). Based on symptomatology, time course and neuropathology, these disorders are quite strictly defined and are each characterized by preferential degeneration within some regions of the CNS with relative preservation within others.