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Herbs with Antidepressant Effects
Published in Scott Mendelson, Herbal Treatment of Major Depression, 2019
The apparent efficacy of Cimicifuga racemosa in reducing symptoms of menopause has led to suspicion of interactions with estrogen receptors. However, studies showing no effect of extracts on uterine weight or vaginal cellular cornification in female rats has cast doubt on that possibility. On the other hand, extracts have been found to displace ligands from various serotonin receptors, particularly the 5-HT1A and 5-HT7 receptors, where there is evidence of partial agonism. It has been suggested that effects of serotonin in the hypothalamus may mitigate some symptoms of menopause, such as hot flashes. This is likely to be the basis of the relief offered by SSRIs. However, both 5-HT1A and 5-HT7 receptors have been associated with mood effects and MDD.10 A particular molecule, Nω-methylserotonin, has been isolated from extracts of the herb, and it showed extremely high, picomolar affinity for the 5-HT7 receptor and acts as a partial agonist.11 There is compelling evidence that 5-HT7 receptor antagonists may have antidepressant properties. For example, it is thought that 5-HT7 antagonism may contribute to the antidepressant effects of the atypical antipsychotic agent, lurasidone.12 What if any role partial agonist effects at 5-HT7 receptors play in potential antidepressant effects of Cimicifuga racemosa is unclear. Some component of Cimicifuga racemosa also acts as a partial agonist at human mu opiate receptors.13
Third Histamine Receptor: From Discovery to Clinics, Long-Lasting Love Story at INSERM and Bioprojet
Published in Divya Vohora, The Third Histamine Receptor, 2008
In fact we had made serious efforts to clone the receptor since the introduction of molecular biology techniques in our laboratory. Our efforts of homology cloning were based on our initial observation that binding of agonists to the H3 receptor was regulated by guanyl nucleotides, strongly suggesting that this receptor belonged to the superfamily of heptahelical receptors, like the two other histamine receptor subtypes. In fact our fishing expeditions with degenerated probes allowed us to discover the 5-HT6 and 5-HT7 receptor, but not the H3 receptor. The latter was beautifully identified by Lovenberg and colleagues among orphan heptahelical receptors, after expression and characterization of its pharmacological profile. Its sequence is far enough from those of H1R or H2R to explain how it had escaped our valuable efforts of homology cloning.
ENTRIES A–Z
Published in Philip Winn, Dictionary of Biological Psychology, 2003
Note: Selective agonists and antagonists for the 5-ht5A, 5-ht5B, 5-ht6 and 5-HT7 receptors are not yet available. When lower case is used [5ht] it indicates that although receptors have been cloned (see clone), expression of the receptor in whole brain has not yet been achieved.
Has the utilization of serotonin receptor antagonism made an impact on schizophrenia treatment?
Published in Expert Opinion on Pharmacotherapy, 2022
Lurasidone is a representative of the serotonin and dopamine antagonist class. It is characterized by potent antagonism at the serotonin 5-HT7 receptor. Its unique pharmacological profile may be associated with a more pronounced improvement of some hard-to-influence schizophrenic symptoms, such as depression and cognitive dysfunction. This is supported by the improved efficacy of lurasidone compared to placebo in the treatment of depressive symptoms and cognitive dysfunction in comparison with quetiapine [14,15]. In terms of side effects, lurasidone was associated with a significantly lower weight gain but higher rates of akathisia, anxiety, and EPS compared to olanzapine and quetiapine. In a systematic review and meta-analysis of weight gains and metabolic side effects of AAPs, lurasidone was shown to be the treatment with the lowest increase in body weight (0.43 kg); in addition, it was also the only treatment associated with a decrease in total cholesterol and triglycerides and, furthermore, the highest decrease in HDL cholesterol [16].
New investigational agents for the treatment of major depressive disorder
Published in Expert Opinion on Investigational Drugs, 2022
Bartłomiej Pochwat, Anna Julia Krupa, Marcin Siwek, Bernadeta Szewczyk
In contrast to 5-HT4 receptor stimulation, the activation of 5-HT7 receptors induce the opposite effect. In vitro studies show that stimulation of 5-HT7 receptors led to the remodeling of dendritic spine morphology, promoting the development of immature spines with smaller heads and longer necks [112,113] (Figure 2). 5-HT7 receptor KO mice showed antidepressant phenotype in the FST and TST and antidepressant-like phenotype in CUS model [112,114,115]. These results suggest that the blockade of 5-HT7 receptors should induce antidepressant effects. Unfortunately, there are not too many studies devoted to the antidepressant-like activity of 5-HT7 antagonists. The SB 269970 5-HT7 receptor antagonist showed antidepressant-like activity in naive mice in the FST and TST [116]. Moreover, intrahippocampal administration of SB 269970 reduced immobility time in the FST in naive rats [117]. Preclinical studies on the antidepressant-like activity of 5-HT7 receptor antagonists are sparse, especially those conducted in animal models of depression. However, conclusions drawn from the invitro paradigms indicate that blockade of this receptor could be interesting, making this receptor an attractive pharmacological target.
The 5-HT7 receptor antagonist SB-269970 alleviates seizure activity and downregulates hippocampal c-Fos expression in pentylenetetrazole-induced kindled rats
Published in Neurological Research, 2022
Bilal Sahin, Ercan Ozdemir, Erkan Gumus, Mustafa Ergul, Ahmet Sevki Taskiran
GABA, the main inhibitory neurotransmitter of the central nervous system, mainly acts on the GABAA receptor [39]. Biochemical and electrophysiological studies have shown that the pharmacological effects of PTZ are induced by blocking the binding sites of the GABAA receptor complex, known as benzodiazepine recognition sites [40]. Hippocampal GABA levels and number of GABAergic interneurons decreased in PTZ-kindled rats [41,42]. Moreover, Kaura et al. reported a reduction in extracellular GABA levels in kindled rat amygdala [43]. Also, GABA levels in cerebrospinal fluid of patients with epilepsy has been found to be lowered in early studies [44–46]. In a recent study in PTZ-kindling model epilepsy in rats, Taskiran et al. showed that GABA levels in the brain decreased after PTZ-induced seizures. In consistent with their study, in the present study, GABA levels were higher in the PTZ kindled rats [1]. 5-HT7 receptors are involved in serotonergic and GABAergic interactions in certain brain structures. 5-HT7 receptors in the DRN are localized on local GABAergic interneurons, which modulate the activity of 5-HT projection neurons. Thus, the activation of 5-HT7 receptors affects 5-HT release by modulating GABAergic transmission in DRN [47]. Moreover, 5-HT7 receptor activation inhibits GABAergic interneurons that target serotoninergic neurons in the raphe nucleus, and then increases 5-HT release in other areas of the brain [48]. On the other hand, 5-HT7 receptors decrease GABA-dependent currents in neurons of the hypothalamic suprachiasmatic nucleus [49]. Tokarski et al. showed that, in normal rat brain, activation of 5-HT7 receptors have enhanced the frequency of GABA-mediated sIPSCs in hippocampal CA1 neurons [17]. Similarly, in a normal rat globus pallidus, 5-HT7 receptor activation increased GABAergic transmission. However, in the present study, 5-HT7 antagonist SB-266970 increased hippocampal GABA levels. This contrast may be due to changes in brain neuronal circuits in kindling model epilepsy. Moreover, SB-266970 also decreased the spike number and percentage seizure duration, 5-HT7 receptor antagonists may show anti-convulsive properties via GABA mediated mechanism.