Comparisons between the in vitro binding of two substituted benzamides and two butyrophenones to dopamine-D2 receptors in the rat striatum.

The in vitro dopamine-D2 receptor binding profiles of two substituted benzamides (3H-sulpride and 3H-raclopride) and two butyrophenones (3H-spiperone and 3H-domperidone) were compared. 3H-Raclopride, 3H-domperidone and 3H-sulpride labelled approximately the same number of binding sites in the rat striatum, while 3H-spiperone labelled a higher number of binding sites. This latter finding was suggested to be due to the labelling of 5-HT2 receptors in addition to the dopamine-D2 binding sites since the labelling of these 5-HT2 receptors with 3H-spiperone could be avoided by the addition of the 5-HT2 receptor antagonist ketanserin. The inhibition constants (Ki) of the unlabelled compounds were similar to the Kd values obtained in the saturation analyses with 3H-raclopride, 3H-domperidone and 3H-sulpiride but were significantly higher when 3H-spiperone was used as radioligand. Addition of ketanserin to 3H-spiperone made the Ki values more similar to those obtained with the other radioligands. The implications of these findings in testing antidopaminergic activity is discussed.