A COMPARISON OF THE NEURO-ENDOCRINOLOGIC AND TEMPERATURE EFFECTS OF DU-29894, FLESINOXAN, SULPIRIDE AND HALOPERIDOL IN NORMAL VOLUNTEERS

1 Nineteen healthy male volunteers participated in a double-blind, six -way, crossover study. With a separation of 1 week between sessions, v olunteers received randomly one oral dose of each of the following com pounds: 3 or 10 mg of the dopamine (DA(2)) receptor antagonist and ser otonin (5HT(1A)) agonist DU 29894, 1 mg flesinoxan, 400 mg sulpiride, 3 mg haloperidol or placebo. 2 To assess the dopamine (DA(2)) antagoni stic activity of the different compounds, plasma levels of prolactin w ere assessed at pre-dose, 0.5, 1, 2, 3, 4, 6 and 24 h post-dose. To as sess the serotonin (5HT(1A)) agonistic activity, plasma levels of ACTH , cortisol and growth hormone were assessed at the same time-points as well as body temperature; the latter was also assessed 8 h post-dose. Plasma levels of DU 29894 were assessed at pre-dose and 2, 3, 4 and 2 4 h post-dose. 3 Sulpiride, haloperidol and both doses of 3 mg and 10 mg DU 29894 produced statistically significant increases in prolactin levels. The increase produced by 3 mg was roughly equivalent to that p roduced by 3 mg haloperidol whereas the increase produced by 10 mg DU 29894 was significantly larger. 4 Only 10 mg DU 29894 and 1 mg flesino xan produced statistically significant increases in ACTH, cortisol and growth hormone. All compounds either showed a significant attenuation of the normal day time increase of body temperature (3 mg DU 29894, h aloperidol and sulpiride) or a true significant decrease in body tempe rature (10 mg DU 29894 and flesinoxan). 5 In conclusion this study cle arly showed single oral doses of 3 and 10 mg DU 29894 to have both dop amine (DA(2)) antagonistic and serotonin (5HT(1A)) agonistic activity.