The intrastriatal injection of
dopamine-like compounds in the guinea pig caused the development of abnormal
involuntary movements (
dyskinesias) which were observed as facial grimacing, biting/gnawing/licking, severe hear and neck twisting, limb movements, whole
body rocking, head and neck rocking and marked locomotor hyperactivity. With the exception of the whole body and head and neck rocking movements the
dyskinesias were specifically induced by
dopamine-like agents. The most conspicuous
dyskinesias which followed the administration of phenylethylamine derivatives were the movements of biting/gnawing/licking and the development of marked locomotor hyperactivity. This effect was shown to be highly specific for
dopamine. Tetrahydroisoquinohydroxy-1,2,3,4-tetrahydronaphthalene (
ADTN) caused locomotor hyperactivity and gnawing/biting/licking
dyskinesias. Of all compounds investigated 1-(3,4-dihydroxyphenyl)pierazine (DHPP) induced the most marked dyskinetic disturbances upon intrastriatal injection: intense facial grimacing, biting/gnawing/licking, head and neck twisting and limb movements were observed although the locomotor hyperactivity was absent. Of the
1-phenylpiperazine derivatives examined, dyskinetic activity was only demonstrated using compounds with a hydroxyphenyl substitution. Results are discussed in terms of the structure--activity relationships for the stimulation of different types of
dopamine receptive structures within the neostriatum.