Discrimination of neuroleptics by means of their interaction with amfonelic acid: an attempt to characterize the test

Abstract

The non-amphetamine stimulant amfonelic acid (AFA) is known to enhance the effects of haloperidol, trifluoperazine and spiperone but not those of the atypical neuroleptics clozapine, thioridazine, and sulpiride, on the striatal levels of 3,4-dihydroxyphenylacetic acid. Consequently, the interaction between neuroleptics and AFA has been proposed as a test to discriminate typical and atypical neuroleptics. In this study, these findings were confirmed. Essentially the same results were obtained when the levels of homovanillic acid were measured. However, striatal dopamine levels were decreased similarly by combinations of AFA with typical and atypical neuroleptics. A comparison of the results with 17 neuroleptics with their reported clinical liability to cause extrapyramidal symptoms supported the idea that the test may discriminate drugs with a better ratio of therapeutic vs side effects. A series of antidepressants and alpha-noradrenergic antagonists possessing antidopaminergic properties was found to perform like atypical neuroleptics, i.e. their effects on dopamine metabolites were not enhanced by AFA.