Behavioural evidence for central D-2 dopamine receptor agonistic effect by some 2-(fluorohydroxyphenyl)ethylamines.

The IP injection of 2-(4-fluoro-3-hydroxyphenyl)ethylamines. (FDA 24), N-n-propyl-N-(2-phenylethyl)-2-(3-fluoro-4-hydroxyphenyl)ethylamine (FDA 27F) and N-n-propyl-N-(2-phenylethyl)-2-(4-fluoro-3-hydroxyphenyl) ethylamine (FDA 40) into adult male rats induced the stretching and yawning (SY) syndrome, FDA 24 being the least active. Moreover, FDA 27F and FDA 40 potentiated penile erection (PE) with respect to controls. For both signs (PE and SY), FDA 40 was the most potent of the three compounds. These effects, which are considered typical signs of central D-2-dopamine (DA) receptor stimulation, were dose-related and significantly inhibited by pretreatment with the selective D-2 DA antagonist, sulpiride, but not by domperidone, which does not cross the hematoencephalic barrier. In previous binding studies, FDA 27F and FDA 40 showed high affinity and selectivity for D-2 DA receptors, while FDA 24 had a low affinity for both D-1 and D-2 DA receptors. The present data show that FDA 27F and FDA 40 cross the blood-brain barrier and exert an agonistic effect on the central D-2 DA receptors. These results also provide evidence of the value of PE and SY tests as sensitive tools for the study of DA-neurochemical mechanisms.