Biochemical assessment of the central 5-HT agonist activity of RU 24969 (a piperidinyl indole).
The most potent compound of a series of piperidinyl indole derivatives which decrease 5-hydroxyindole acetic acid (5-HIAA) levels in rat brain-stem was chosen for further study on the neurochemistry of serotonin (5-HT) neurons. This derivative (RU 24969: 5-methoxy 3-(1,2,3,6-tetrahydro-4-pyridinyl) 1 H indole, succinate) exerted a dose-dependent reduction in 5-HIAA concentrations in rat forebrain and brain-stem, which was of rapid onset and lasted for at lest 4 h. The decrease in 5-HIAA was apparently due to a decrease in 5-HT turnover since RU 24969 significantly diminished 5-HTP accumulation after RO 4-4602 administration, and 5-HIAA accumulation after probenecid treatment. Basal or 5-HT-stimulated adenylate cyclase activities in colliculi from new-born rats were unaffected by RU 24969. This compound increased serum prolactin and corticosterone levels in a dose-related manner. Together with previous behavioral observations and the potent displacement of [3H]-5-HT binding obtained with this series, the present data indicate that these new piperdinyl indole derivatives are likely potent 5-HT receptor agonists in rat brain.
D006916:5-Hydroxytryptophan / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects*; D003345:Corticosterone / Q000097:blood; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D010902:Pituitary Gland / Q000502:physiology; D011339:Probenecid / Q000494:pharmacology; D011388:Prolactin / Q000097:blood; D051381:Rats; D011985:Receptors, Serotonin / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*
D007211:Indoles; D011985:Receptors, Serotonin; C025145:5-methoxy 3-(1,2,3,6-tetrahydro-4-pyridinyl)1H indole; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D011388:Prolactin; D006916:5-Hydroxytryptophan; D000262:Adenylyl Cyclases; D011339:Probenecid; D003345:Corticosterone