The Neurochemical Basis of Acetylcholine Precursor Loading as a Therapeutic Strategy

Abstract

With the recognition that deficits in central cholinergic function may play a role in several pathological states (Davis et al., 1975b; Van Woert, 1976; Weiss et al., 1976; Aquilonius, 1977; Davis et al., 1977a; Drachman, 1977; Eckernas, 1977; Jenden, 1977a; Barbeau, 1978; Davis and Berger, 1978; Davis et al., 1978b), increasing attention has been directed to the possibility that administration of metabolic precursors of acetylcholine (ACh) may promote its synthesis, availability and utilization. This therapeutic strategy is certainly effective in the treatment of disorders characterized by deficits in the synthesis and metabolism of other neurotransmitters, particularly dopamine (Barbeau, 1976; Growdon et al., 1977a). At present there is suggestive although not compelling evidence of causative associations between cholinergic deficits and several clinical illnesses. There is very little information regarding the possible mechanisms by which administration of ACh precursors favors the synthesis and utilization of ACh, and whether other less direct mechanisms underlie the therapeutic successes which have been reported. In this chapter the origins of the choline (Ch) and acetyl moieties will be reviewed, with particular reference to ACh synthesis in the brain and its regulation. The experimental, clinical and laboratory evidence of the impact of precursor loading will be examined and some of the more promising directions for future research in this area will be identified.