Amphetamine-induced stereotyped behavior in animals and tardive dyskinesias in humans are both related to the activity of dopamine at striatal dopamine receptors. Antichlinergic agents potentiate the stereotyped behavior induced by amphetamines. Anticholinergic agents, as well as prolonged chlorpromazie pretreatment, decrease the threshold for ampheramine-induced stereotyped behavior.
These observations have several implications for tardive dydkinesias in man. Anticholinergic medications should worsen tardive dyskinesias. Anticholinergics may also decrease the threshold for tardive dyskinesias, thereby increasing the incidence of the disorder. Patients who have a subclinical abnormality of the dopaminergic receptors may manifest this movement disorder only when given anticholinergic medication.
It is suggested that patients on long-term neuroleptic therapy not be routinely given anticholinergic agents, since these drugs worsen tardive duskinesias in patients who have this disorder and may increase the incidence of tardive dyskinesias in patients receiving neuroleptics.
Rubovits R, Klawans HL. Implications of Amphetamine-Induced Stereotyped Behavior as a Model for Tardive Dyskinesias. Arch Gen Psychiatry. 1972;27(4):502-507. doi:10.1001/archpsyc.1972.01750280070012