[Tardive dyskinesia: I. Physiopathology and treatment]

The major breakthrough in the treatment of mental diseases was the introduction of neuroleptics in the early 50's. Soon after this an increasing number of patients under the use of these drugs presented involuntary abnormal orofacial movements which have been considered directly dependent on the drug action. The term "tardive dyskinesia" (TD) was coined for these movements. Many theories have been put forward to explain the pathophysiology of TD. The most prominent theory concerns with the possibility of denervation hypersensitivity occurring in striatal post-synaptic dopamine neurons. The authors review the most important theories and offer a new possibility based on the assumption that the post-synaptic dopamine receptors under chronic neuroleptic action develop a shift in its affinity towards the direction of agonist action. This means that the post-synaptic receptor increase its affinity, and possibly its number, to agonist drugs and dopamine. The paper includes a review of the main drugs used in this condition, attempting to explain the specific sites where they act, either in the dopaminergic, cholinergic or GABA--ergic systems.