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Studies on the Mechanism of Action of Substituted Benzamide Drugs
Author(s) -
Köhler Christer,
Ögren SvenOve,
Fuxe Kjell
Publication year - 1984
Publication title -
acta psychiatrica scandinavica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.849
H-Index - 146
eISSN - 1600-0447
pISSN - 0001-690X
DOI - 10.1111/j.1600-0447.1984.tb06864.x
Subject(s) - spiperone , sulpiride , tiapride , chemistry , chlorpromazine , apomorphine , dopamine receptor , haloperidol , striatum , dopamine antagonist , pharmacology , agonist , thioridazine , benzamide , dopamine , medicine , antagonist , endocrinology , stereochemistry , receptor , biochemistry
The effects of classical neuroleptic drugs (haloperidol, chlorpromazine) and atypical neuroleptics, i.e. substituted benzamides (L‐sulpiride, tiapride, FLA 731(‐)) on specific in vivo binding of the dopamine antagonist 3 H‐spiperone and the dopamine agonist 3 H‐n‐propylnorapomorphine ( 3 H‐NPA) was examined in male rats. The atypical neuroleptics were found to be considerably more potent in displacing nigral than striatal 3 H‐spiperone binding while the classical neuroleptics were about equipotent in the two brain regions. The benzamides also produced considerably less displacement of 3 H‐spiperone in the striatum than did classical neuroleptics. Furthermore, while the classical neuroleptic drugs block the striatal 3 H‐spiperone and 3 H‐NPA binding sites to about the same degree, the substituted benzamides appear to have a higher affinity for the DA receptors labelled by 3 H‐NPA than those labelled by 3 H‐spiperone. The behavioural effects of the benzamides were found to differ from classical neuroleptic drugs particularly with regard to induction of catalepsy. Thus, the induction of cataleptic behaviour was found to correlate with displacement of 3 H‐spiperone in the striatum while blockade of apomorphine induced hyperactivity correlated with the displacement of spiperone in extrastriatal areas.