Involvement of 5-HT2 receptors in the LSD- and L-5-HTP-induced suppression of lordotic behavior in the female rat

Sietnieks, Anni

doi:10.1007/bf01253052

Cited by 16 publications

(7 citation statements)

References 29 publications

(38 reference statements)

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“…Application of the 5-HT 2A R-antagonist Altanserin hydrochloride (8.0 µg/ml, n = 3) [32], [45] significantly reduced the amplitude from control of 100% to 52.34±4.72% (p<0.01), while breathing frequency increased from control of 10.25±0.63 to 14.50±3.59 bursts/min; n.s. (fig.…”

Section: Resultsmentioning

confidence: 94%

Expression and Function of Serotonin 2A and 2B Receptors in the Mammalian Respiratory Network

et al. 2011

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Neurons of the respiratory network in the lower brainstem express a variety of serotonin receptors (5-HTRs) that act primarily through adenylyl cyclase. However, there is one receptor family including 5-HT2A, 5-HT2B, and 5-HT2C receptors that are directed towards protein kinase C (PKC). In contrast to 5-HT2ARs, expression and function of 5-HT2BRs within the respiratory network are still unclear. 5-HT2BR utilizes a Gq-mediated signaling cascade involving calcium and leading to activation of phospholipase C and IP3/DAG pathways. Based on previous studies, this signal pathway appears to mediate excitatory actions on respiration. In the present study, we analyzed receptor expression in pontine and medullary regions of the respiratory network both at the transcriptional and translational level using quantitative RT-PCR and self-made as well as commercially available antibodies, respectively. In addition we measured effects of selective agonists and antagonists for 5-HT2ARs and 5-HT2BRs given intra-arterially on phrenic nerve discharges in juvenile rats using the perfused brainstem preparation. The drugs caused significant changes in discharge activity. Co-administration of both agonists revealed a dominance of the 5-HT2BR. Given the nature of the signaling pathways, we investigated whether intracellular calcium may explain effects observed in the respiratory network. Taken together, the results of this study suggest a significant role of both receptors in respiratory network modulation.

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Section: Resultsmentioning

confidence: 94%

Expression and Function of Serotonin 2A and 2B Receptors in the Mammalian Respiratory Network

et al. 2011

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“…1983b;Mokler et al 1983;Trulson et al 1983;Heym et al 1984;Colpaert etal. 1985;Glennon and Hauck 1985;Mokler et al 1985;Nielsen et al 1985;Sietnieks 1985). Because these same antagonists were ineffective in blocking the pre-synaptic actions of indole hallucinogens (Haigler and Aghajanian 1974b), the behavioral effects of hallucinogens, like the electrophysiological effects on motor neurons, were more easily ascribed to actions on postsynaptic 5-HT receptors.…”

mentioning

confidence: 99%

Mescaline: excitatory effects on acoustic startle are blocked by serotonin2 antagonists

Davis

1987

Psychopharmacology

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The ability of serotonin2 (5-HT2) antagonists to block the excitatory effects of mescaline on the acoustic startle reflex were analyzed. Mescaline (20 mg/kg) caused a consistent increase in the amplitude of the acoustic startle reflex. This effect was blocked in a dose-related fashion by the 5-HT2 antagonist ritanserin (ED50 dose = 0.25 mg/kg IP). In contrast, even a high dose of ritanserin (2.0 mg/kg) did not block the excitatory effects of amphetamine on startle. Other 5-HT2 antagonists (ketanserin, cinanserin, LY 53857) also blocked mescaline's effect, whereas the 5-HT1 antagonist pindolol (5 mg/kg) did not. These results support the hypothesis that the behavioral effects of hallucinogens are mediated by agonist actions at 5-HT2 receptors.

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“…We manually examined the high-scoring compounds based on in silico estimations of binding strength, appropriate molecular weight and other drug-like properties, and complementary matching of molecular shape. The highest-scoring compounds were identi ed and nine commercially available compounds (Table 1) were selected for subsequent validations [30][31][32][33][34][35][36][37][38] [38] An idock score is the estimated binding free energy (kcal/mol units). Negative value implies a high predicted binding a nity.…”

Section: Discovery Of Cdk2/4/6 Triple-inhibitors Via Computer-aided Smentioning

confidence: 99%

Discovery of Vanoxerine Dihydrochloride as a CDK2/4/6 Triple-Inhibitor for the Treatment of Human Hepatocellular Carcinoma

Zhu

Shi

Xia

et al. 2020

Preprint

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Background Cyclin-dependent kinases 2/4/6 (CDK2/4/6) play critical roles in cell cycle progression, and their deregulations are hallmarks of hepatocellular carcinoma (HCC).Methods Here we combined computational and experimental approaches to discover a CDK2/4/6 triple-inhibitor from FDA approved small-molecule drugs for the treatment of HCC.Results Based on molecular docking results, vanoxerine dihydrochloride was found to exhibit strongest cytotoxic effect on human HCC QGY7703 and Huh7 cells (IC50: 3.79 µM for QGY7703and 4.04 µM for Huh7 cells). Vanoxerine dihydrochloride treatment caused G1arrest, induced apoptosis, and reduced the expressions of CDK2/4/6, cyclin D/E, retinoblastoma protein (Rb), as well as the phosphorylation of CDK2/4/6 and Rb in QGY7703 and Huh7 cells. In addition, combined vanoxerine dihydrochloride and 5-Fu produced synergistic cytotoxicity in Huh7 cells. Finally, in vivo studies in preclinical animal model of BALB/C mice subcutaneously xenografted with Huh7 cells, we showed that injection of vanoxerine dihydrochloride (40 mg/kg, i.p.) produced significant antitumor activity (p < 0.05), comparable to that achieved by 5-Fu (10 mg/kg, i.p.), with the combination treatment resulted in strongest effect.Conclusions The present study is the first to identify a CDK2/4/6 triple inhibitor vanoxerine dihydrochloride, and demonstrate that it represents a novel therapeutic strategy for HCC treatment alone or in combination with 5-Fu.

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Involvement of 5-HT2 receptors in the LSD- and L-5-HTP-induced suppression of lordotic behavior in the female rat

Cited by 16 publications

References 29 publications

Expression and Function of Serotonin 2A and 2B Receptors in the Mammalian Respiratory Network

Expression and Function of Serotonin 2A and 2B Receptors in the Mammalian Respiratory Network

Mescaline: excitatory effects on acoustic startle are blocked by serotonin2 antagonists

Discovery of Vanoxerine Dihydrochloride as a CDK2/4/6 Triple-Inhibitor for the Treatment of Human Hepatocellular Carcinoma

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