Choline Availability and the Synthesis of Acetylcholine

Most of the work on transmitter replacement therapy by means of precursor loading has been directed toward manipulation of neurotransmitters synthesized from aromatic amino acids (47). However, beginning in the mid 1970’s, clinical investigators became interested in the use of choline (Ch) to treat disorders in which too little acetylcholine (ACh) was formed in the brain, or in which the formation of an excess of the neurotransmitter was believed to be desirable. This interest in Ch as a therapeutic agent was triggered by basic research showing that the administration of Ch to laboratory animals could cause an increase in the level of ACh in the brain, a phenomenon first described in 1972 by Kuntscherova (32). Although the beneficial effects of Ch in some disorders such as tardive dyskinesia (see 2) may reside in other properties of the molecule (e.g. a direct postsynaptic muscarinic action of Ch has been demonstrated (9,20,31)), there is evidence that part of the effect of Ch is elicited through stimulation of ACh synthesis and release. This evidence is reviewed in the first part of this report.