Dyskinetic phenomena caused by the intrastriatal injection of phenylethylamine, phenylpiperazine, tetrahydroisoquinoline and tetrahydronaphthalene derivatives in the guinea pig

Abstract

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 head 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. Tetrahydroisoquinoline derivatives were generally only weakly active and of the tetrahydronaphthalenes tested only 2-amino-6,7-dihyroxyl-1,2,3,4-tetrahydronaphthalene (ADTN) caused locomotor hyperactivity and gnawing/biting/licking dyskinesias. Of all compounds investigated 1-(3,4-dihydroxyphenyl)piperazine (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 l-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.