Effects of ritanserin, a novel serotonin-s2 receptor antagonist, on the secretion of pituitary hormones in normal humans

Abstract

The availability of a new potent and selective serotonin-S2 antagonist, ritanserin (RIT), encouraged us to further investigate the effect of serotonin on the basal secretion of anterior pituitary hormones in normal humans. Administered in a single 30-mg dose to group 1 consisting of 10 normal women, RIT failed to affect the baseline LH, FSH, GH or TSH levels. In group 2 consisting of 20 normal subjects (ten males and ten females), the same dose of RIT decreased in parallel both ACTH and cortisol levels but only at 180 min. Group 3 consisting of 8 normal men was studied on three separate occasions seven days apart: each subject received graded doses of 10 mg, 20 mg and 30 mg RIT. The mean baseline PRL concentration at 180 min as well as the net integrated area under the hormone curve (nAUC) decreased only after the highest dose, while the baseline cortisol concentrations at 180 min as well as the corresponding nAUC values displayed a clear dose-dependent response. The findings indicated the serotonin-S2 receptors to be only partially involved in the basal secretion of ACTH in normal humans.

Activation of the JAK-STAT pathway by olanzapine is necessary for desensitization of serotonin2A receptor-stimulated phospholipase C signaling in rat frontal cortex but not serotonin2A receptor-stimulated hormone release

“…Studies have also demonstrated that the atypical antipsychotic-induced decrease in cortisol levels is associated with an improvement in psychopathology (Hatzimanolis, et al, 1998)(Markianos, et al, 2001). The olanzapine-induced decrease in plasma levels of oxytocin, ACTH, and corticosterone in this study are consistent with previous reports (Scheepers, et al, 2001a;Tepavcevic, et al, 1994) and suggest that chronic olanzapine-treatment produced a functional desensitization of 5-HT 2A receptors in PVN as well. However, unlike in the frontal cortex where preinjections of AG490 significantly attenuated the olanzapine-induced decrease in 5-HT 2A receptor-mediated PLC activity, olanzapine-induced desensitization of 5-HT 2A receptor stimulated plasma hormone release was not affected by inhibition of JAK-STAT signaling pathway.…”

Ziprasidone decreases cortisol excretion in healthy subjects

“…Premedication with the 5-HT2A/C antagonist ritanserin attenuates the MCPP-and 5-HT-induced increases in cortisol [24,34] although some studies have reported suppressed elevation of cortisol concentrations by ritanserin through a mechanism involving 5-hydroxytryptophan [35]. Furthermore, ritanserin given as a single dose decreases ACTH and cortisol concentrations [36], and the marked increase in corticosteroid concentrations produced by fenfluramine and quipazine are abolished by pretreatment with ketanserin [37]. Recently, further consideration of the effects of 5-HT agonists indicated that 5-HT2A receptors rather than 5-HT2C receptors play an important role in mediating increases in rat serum corticosterone concentrations [25,38].…”

Der Einfluss von Ziprasidon auf den Schlaf und die Kortisolexkretion

“…ACTH-Sekretion bei gesunden Probanden untersucht. Die Gabe einer Einzeldosis Ritanserin, einem 5-HT 2A /5-HT 2C -Antagonisten, zeigt einen ACTH-senkenden und kortisolsenkenden Effekt (Tepavcević et al, 1994). In einer anderen Studie hat eine längerfristige Ritanserin-Applikation keinen Einfluss auf die basale Hormonsekretion, kann jedoch eine Kortisolssekretion, die durch eine Insulin-induzierte Hypoglykämie hervorgerufen worden ist, abschwächen (Tepavcević et al, 1995).…”