Amantadine reduces haloperidol-induced dopamine receptor hypersensitivity in the striatum.

In this report evidence is presented that amantadine hydrochloride greatly reduced the development of dopaminergic receptor hypersensitivity in the striatum, which normally results following chronic haloperidol administration using both a stereotyped behavior bioassay and a [3H]spiroperidol receptor binding assay. Amantadine prophylaxis reduced maximal ligand binding to near control levels and also significantly reduced apomorphine induced stereotypy. These results clearly demonstrate that amantadine greatly reduced haloperidol-induced striatal dopamine receptor hypersensitivity and support the hypothesis that amantadine given concurrently with neuroleptic agents might serve to prevent the development of human tardive dyskinesia.