作者: Nasr, Suhayl ; Meltzer, Herbert Y. ; Jayathilake, Karu ; Arshadi, Mahdi ; Drevets, Wayne C. ; Rassnick, Stefanie ; Ford, Lisa ; Elmaadawi, Ahmed Z.

BackgroundThe serotonin type 7 (5-HT7) receptor is one of 14 5-HT receptors. It has received attention for its possible role in mood disorders and cognition. The 5-HT7 receptor antagonist, JNJ-18038683, has been reported to be effective in rodent models of depression and REM sleep. Also, 5-HT7 receptor blockade has been postulated to be a key component of cognitive enhancement in a number of drugs. Bipolar disorder (BD) usually endures cognitive impairment (CI); however, no treatment for CI in BD has been approved. This study aimed to evaluate the efficacy of JNJ-18038683 to improve the CI of BD compared to a placebo.MethodsWe conducted a placebo-controlled, 8-week trial of JNJ-18038683 in BD patients. Each patient's data were analyzed and reassessed blindly with a comprehensive neuropsychological battery, depression and hypomania ratings, and overall social and work function measures.ResultsOf 60 patients, 38 (63%) were female, 43 (72%) had BD type 1, and most patients were Caucasian and married. The overall time effect for the combined group shows statistically significant improvement from baseline to week 8 for most of the neurocognitive battery measures. This indicates a significant improvement in psychopathology and cognition during the study time in both JNJ-18038683 and placebo groups, but no difference between groups.ConclusionsThis study showed no efficacy for the improvement of CIBD or mood symptoms with JNJ-18038683 compared to the placebo.

2024-07-01·Toxicology Letters

Effects of psilocin and psilocybin on human 5-HT4 serotonin receptors in atrial preparations of transgenic mice and humans

Article

作者: Hofmann, Britt ; Azatsian, Karyna ; Neumann, Joachim ; Gergs, Ulrich ; Dimov, Kiril

Several fungi belonging to the genus Psilocybe, also called "magic mushrooms", contain the hallucinogenic drugs psilocybin and psilocin. They are chemically related to serotonin (5-HT). In addition to being abused as drugs, they are now also being discussed or used as a treatment option for depression. Here, we hypothesized that psilocybin and psilocin may act also on cardiac serotonin receptors and studied them in vitro in atrial preparations of our transgenic mouse model with cardiac myocytes-specific overexpression of the human 5-HT₄ receptor (5-HT₄-TG) as well as in human atrial preparations. Both psilocybin and psilocin enhanced the force of contraction in isolated left atrial preparations from 5-HT₄-TG, increased the beating rate in isolated spontaneously beating right atrial preparations from 5-HT₄-TG and augmented the force of contraction in the human atrial preparations. The inotropic and chronotropic effects of psilocybin and psilocin at 10 µM were smaller than that of 1 µM 5-HT on the left and right atria from 5-HT₄-TG, respectively. Psilocybin and psilocin were inactive in WT. In the human atrial preparations, inhibition of the phosphodiesterase III by cilostamide was necessary to unmask the positive inotropic effects of psilocybin or psilocin. The effects of 10 µM psilocybin and psilocin were abrogated by 10 µM tropisetron or by 1 µM GR125487, a more selective 5-HT₄ receptor antagonist. In summary, we demonstrated that psilocin and psilocybin act as agonists on cardiac 5-HT₄ receptors.

2024-07-01·Neurochemistry International

Lateral habenula 5-HT1B receptors are involved in regulation of anxiety-like behaviors in parkinsonian rats

Article

作者: Yang, Jie ; Guo, Yuan ; Wang, Yixuan ; Gao, Shasha ; Tang, Guoyi ; Liu, Jian ; Li, Ruotong

Although the output of the lateral habenula (LHb) controls the activity of midbrain dopaminergic and serotonergic systems, which are implicated in the pathophysiology of anxiety, it is not clear the role of LHb 5-HT_1B receptors in regulation of anxiety-like behaviors, particularly in Parkinson's disease-related anxiety. In this study, unilateral 6-hydroxydopamine lesions of the substantia nigra pars compacta in rats induced anxiety-like behaviors, led to decreased normalized δ power and increased normalized θ power in the LHb, and decreased dopamine (DA) level in the prelimbic cortex (PrL) compared with sham rats. Down-regulation of LHb 5-HT_1B receptors by RNA interference produced anxiety-like effects, decreased normalized δ power and increased normalized θ power in the LHb in both sham and lesioned rats. Further, intra-LHb injection of 5-HT_1B receptor agonist CP93129 induced anxiolytic-like responses, increased normalized δ power and decreased normalized θ power in the LHb, and increased DA and serotonin (5-HT) release in the PrL; conversely, 5-HT_1B receptor antagonist SB216641 produced anxiety-like effects, decreased normalized δ power and increased normalized θ power in the LHb, and decreased DA and 5-HT release in the PrL in sham and lesioned rats. Additionally, effects of CP93129 and SB216641 on the behaviors, normalized δ and θ power in the LHb, and DA and 5-HT release in the PrL were decreased in lesioned rats, which were consistent with down-regulation of LHb 5-HT_1B receptors after DA depletion. Collectively, these findings suggest that 5-HT_1B receptors in the LHb are involved in the regulation of anxiety-like behaviors.

100 项与 5-HT7 receptor antagonists(Egis Gyógyszergyár Zrt) 相关的药物交易

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