Pharmacological investigations of the cholinergic imbalance hypotheses of movement disorders and psychosis.

The hypotheses of relative cholinergic underactivity in Huntington's disease, tardive dyskinesia, mania, and schizophrenia were pharmacologically investigated, using physostigmine and choline chloride. Intravenous physostigmine improved the involuntary movements of all of four patients with tardive dyskinesia and three of six patients with Huntington's disease. Physostigmine infusion also decreased manic symptoms in six of nine patients with mania, but had no beneficial effects in three patients with schizophrenia. Precursorloading with choline chloride may increase brain acetylcholine levels and central cholinergic activity. In patients with movement disorders a transient improvement during physostigmine infusion predicted a positive response to a trial of oral choline chloride. One manic patient may have been improved by choline chloride, however choline chloride did not improve symptoms in four of six schizophrenix patients. Chronic treatment with oral choline chloride increases plasma levels of choline during administration and for approximately 48 hr after discontinuation of treatment. A single 5-g dose of choline chloride also transiently raises plasma choline levels. These results with physostigmine support the hypotheses of cholinergic underactivity in Huntington's disease, tardive dyskinesia, and mania. Agents which might chronically increase cholinergic activity such as choline chloride should be further tested in these disorders.