A comparison of the neuro-endocrinological 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, volunteers received randomly one oral dose of each of the following compounds: 3 or 10 mg of the dopamine (DA2) receptor antagonist and serotonin (5HT1A) agonist DU 29894, 1 mg flesinoxan, 400 mg sulpiride, 3 mg haloperidol or placebo. 2. To assess the dopamine (DA2) antagonistic activity of the different compounds, plasma levels of prolactin were assessed at pre-dose, 0.5, 1, 2, 3, 4, 6 and 24 h post-dose. To assess the serotonin (5HT1A) 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 24 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 produced 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 flesinoxan 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, haloperidol and sulpiride) or a true significant decrease in body temperature (10 mg DU 29894 and flesinoxan).(ABSTRACT TRUNCATED AT 250 WORDS)
de Koning
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Department of Clinical Pharmacology, Solvay Duphar B.V., Weesp, The Netherlands.
de Vries
M H
MH
D000284:Administration, Oral; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D001831:Body Temperature / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D018492:Dopamine Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D013006:Growth Hormone / Q000097:blood; D006220:Haloperidol / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D011388:Prolactin / Q000097:blood; D011863:Radioimmunoassay; D017366:Serotonin Receptor Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D013469:Sulpiride / Q000008:administration & dosage / Q000494:pharmacology
C093665:DU 29894; D018492:Dopamine Antagonists; D010879:Piperazines; D017366:Serotonin Receptor Agonists; C056895:flesinoxan; D013469:Sulpiride; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D013006:Growth Hormone; D006220:Haloperidol; D006854:Hydrocortisone