Cholinergic strategies in Tourette Syndrome: A Controlled Trial of Tacrine Hydrochloride

Grant Type
Grant Year
Institution Location
Institution Organization Name
Emory University
Investigators Name
Juncos, Jorge, MD

Tourette Syndrome (TS) may result in part from excessive dopaminergic activity in the brain. This assumption is based on the experience that drugs which affect this system can alleviate or aggravate TS. In spite of this pharmacologic evidence, there has been surprisingly little evidence from blood or autopsy studies to support this view. In addition, treatments based on dopamine blockade do little for the attention deficit disorders (ADD), learning disabilities (LD) and obsessive compulsive symptoms (OCS) associated with TS. A possible explanation for these discrepancies may be that the role of dopamine in TS is indirectly mediated by abnormalities in other chemical systems that secondarily affect dopamine. For in¬stance, the symptoms of TS may be associated with dysfunction in the brain’s cholinergic system, a system that uses acetylcholine as its transmitter. Dopamine and acetylcholine have complementary roles that are thought to “balance” each other’s effects on the brain. Consequently dopaminergic “hyperfunction” could be the direct result of too much dopamine, or the indirect result of too little acetylcholine in the brain. Drugs that help restore this balance may help alleviate primary TS symptoms, as well as those of ADD, LD, and OCS which are inadequately responsive to current therapies. We do have indirect evidence for possible abnormalities in brain cholinergic activity in TS. Previously tested drugs designed to restore this balance by increasing brain acetylcholine have yielded mixed results in TS, presumably due to their low potency, short action and frequent side effects. We will conduct an open-label dose-finding trial of a currently available cholinergic agent, tacrine hydrochloride (Cognex), in a select group of moderately affected adult patients with TS. Compared to previously tested cholinergic agents, tacrine is more potent, longer acting and may be better tolerated. The major goal of this study is to determine whether examination of tacrine, or other cholinergic augmentation strategies under development, is justified in a larger double-blind placebo controlled trial. Jorge L. Juncos, M.D., Vicki J. Roberts, Ph.D. Emory University School of Medicine Atlanta, GA Award $25,000 Tourette Association of America Inc. – Research Grant Award 1996