Topic
Eptapirone
About: Eptapirone is a research topic. Over the lifetime, 4 publications have been published within this topic receiving 146 citations.
Papers
TL;DR: The pharmacology of 5-HT1A receptor ligands seems to be codetermined by the effector pathway as differences between ligands that seem small in the [35S]GTPγS binding assay translate into huge differences in the magnitude of Ca2+ responses.
Abstract: Little experimental evidence has been reported for diverse signaling via 5-hydroxytryptamine (5-HT)1A receptors despite the fact that agonists seem to be more efficacious at dorsal raphe somatodendritic 5-HT1A autoreceptors than at postsynaptic 5-HT1A receptors. The present study investigated Ca2+ responses in Chinese hamster ovary (CHO)-K1 cells expressing a human 5-HT1A receptor by 5-HT, prototypical 5-HT1A agonists, N- (3-chloro-4-fluorobenzoyl)-4-fluoro-4-[(5-methyl-6-; methylaminopyridin-2-yl)-methylaminomethyl]-piperidine (F 14679), and especially N- (3-chloro-4-fluorobenzoyl)-4-fluoro-4-[(5-methylpyridin-2-yl)-; methylaminomethyl]piperidine (F 13640) as representative ligands of a new chemical class (methylamino-pyridine) that combines both high efficacy and selectivity for 5-HT1A receptors. 5-HT (pEC50 = 6.70 ± 0.02) induced a pertussis toxin-sensitive, transient high-magnitude Ca2+ response. High-magnitude Ca2+ responses ( E max, percentage versus 5-HT) were also found with F 13640 (107 ± 4), 5-carboxamidotryptamine (100 ± 3), and F 14679 (87 ± 3). In contrast, the prototypical 5-HT1A receptor agonists buspirone, ipsapirone, and 8-(hydroxy-2-(di- n -propylamino)tetralin, and also flesinoxan and eptapirone, were virtually inactive (≤5). This atypical pattern of 5-HT1A receptor activation contrasts with the broad spectrum of the ligands' partial agonist properties as observed by measuring guanosine 5′- O -(3-[35 S]thio)triphosphate ([35S]GTPγS) binding responses with membranes of either CHO-K1 or C6-glial cells stably expressing a human 5-HT1A receptor. Remarkably, differences between ligands that seem small in the [35S]GTPγS binding assay translate into huge differences in the magnitude of Ca2+ responses. Therefore, some of these 5-HT1A ligands (i.e., F 13640) may in a selective way induce responses that may be not at all be achieved with other ligands (i.e., buspirone). In conclusion, the pharmacology of 5-HT1A receptor ligands seems to be codetermined by the effector pathway.
25 citations
TL;DR: The highest intrinsic activity 5-HT1A receptor ligands, F 13714, maximally inhibited haloperidol-induced catalepsy in the cross-legged position and bar tests, likely has marked anti-cataleptic effects because of its high intrinsic activity at 5- HT1A receptors.
TL;DR: REM sleep was significantly suppressed supporting the proposition that activation of post-synaptic 5HT1A receptors reduces REM sleep, and sleep fragmentation increased by both drugs.
Abstract: The partial agonist buspirone has a REM (rapid eye movement) suppressing effect on human sleep probably via a 5HT1A receptor in the pontine area. Eptapirone is a new 5HT1A agonist with a greater intrinsic effect than buspirone. The objective of this study was to examine the effects of eptapirone on sleep architecture, particularly REM sleep, in normal volunteers and compare it with buspirone and placebo. This was a randomized, double-blind placebo-controlled four-way crossover study in 12 healthy volunteers. Volunteers were screened to ensure that they had normal overnight sleep EEG (electroencephalogram) and were extensive CYP 2D6 metabolizers. Sleep was recorded on pairs of nights on four occasions, with medication being taken before the second night. Treatments were eptapirone 1.5mg at 10 AM, eptapirone 1.5mg at 11 PM, buspirone 20mg at 11 PM and placebo. Standard measures of sleep were derived and compared among the four treatments using ANOVA. REM sleep was significantly suppressed supporting the pro...
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2005 | 2 |
| 2003 | 1 |
| 2002 | 1 |