Repurposing the Antipsychotic Drug Chlorpromazine as Adjuvant Therapeutic Agent for Resected Stage III Colon Cancer: A Pilot, Randomized, Open Label, Controlled Study.

chlorpromazine displays a series of remarkable bio-molecular effects in cancer cells, as inhibition of cell growth, nuclear aberrations, inhibition of the phosphoinositide 3-kinase/mammilian target of rapamycin (PI3K/mTOR) axis, induction of cytotoxic autophagy, inhibition of glutamate and DRD2 receptors. This study will evaluate the addition of chlorpromazine to the first-line therapeutic protocol in colon cancer stage III.

开始日期2022-07-20

申办/合作机构

University of Sadat City

IRCT20200913048708N1 / Suspended临床2期IIT

Evaluation of efficacy and safety of adding Chlorpromazine to Atazanavir/Ritonavir regimen in the treatment of COVID-19 patients, a randomized double-blind clinical trial

开始日期2020-10-31

申办/合作机构

Mazandaran University of Medical Sciences

IRCT20090726002232N4 / Completed临床2/3期IIT

Comparison of Haloperidol, Promethazine, Triflupeazine and Chlorpromazine in terms of velocity and durability of the sedation among acute aggressive patients

开始日期2017-12-22

申办/合作机构

Isfahan University of Medical Sciences

100 项与 ADRA2 x D2 receptor x Histamine receptor 相关的临床结果

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100 项与 ADRA2 x D2 receptor x Histamine receptor 相关的转化医学

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0 项与 ADRA2 x D2 receptor x Histamine receptor 相关的专利（医药）

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项与 ADRA2 x D2 receptor x Histamine receptor 相关的文献（医药）

2011-05-01·Pain1区 · 医学

Influence from genetic variability on opioid use for cancer pain: A European genetic association study of 2294 cancer pain patients

1区 · 医学

Article

作者: R. Sabatowski ; O. Dale ; Kristin Bjordal ; S. Kaasa ; V. Sigurdardottir ; S. Lundström ; L. Radbruch ; A. Caraceni ; F. Strasser ; F. Skorpen ; A. Davies ; M. Kloke ; M. Maltoni ; T. Fladvad ; P. M. Fayers ; P. Klepstad

Cancer pain patients need variable opioid doses. Preclinical and clinical studies suggest that opioid efficacy is related to genetic variability. However, the studies have small samples, findings are not replicated, and several candidate genes have not been studied. Therefore, a study of genetic variability with opioid doses in a large population using a confirmatory validation population was warranted. We recruited 2294 adult European patients using a World Health Organization (WHO) step III opioid and analyzed single nucleotide polymorphisms (SNPs) in genes with a putative influence on opioid mechanisms. The patients' mean age was 62.5 years, and the average pain intensity was 3.5. The patients' primary opioids were morphine (n=830), oxycodone (n=446), fentanyl (n=699), or other opioids (n=234). Pain intensity, time on opioids, age, gender, performance status, and bone or CNS metastases predicted opioid dose and were included as covariates. The patients were randomly divided into 1 development sample and 1 validation sample. None of 112 SNPs in the 25 candidate genes OPRM1, OPRD1, OPRK1, ARRB2, GNAZ, HINT1, Stat6, ABCB1, COMT, HRH1, ADRA2A, MC1R, TACR1, GCH1, DRD2, DRD3, HTR3A, HTR3B, HTR2A, HTR3C, HTR3D, HTR3E, HTR1, or CNR1 showed significant associations with opioid dose in both the development and the validation analyzes. These findings do not support the use of pharmacogenetic analyses for the assessed SNPs to guide opioid treatment. The study also demonstrates the importance of validating findings obtained in genetic association studies to avoid reporting spurious associations as valid findings. To elicit knowledge about new genes that influence pain and the need for opioids, strategies other than the candidate gene approach is needed.

2008-12-01·Neuropsychopharmacologia Hungarica : a Magyar Pszichofarmakologiai Egyesulet lapja = official journal of the Hungarian Association of Psychopharmacology

Quetiapin alkalmazása bipoláris zavarban.

Review

作者: Sümegi, András

Atypical antipsychotics are now widely used in the acute and long-term treatment in bipolar disorder. The role of atypical antipsychotics as acute agents, add-on medications; or as primary mood stabilizers in different phases of bipolar disorder is an important current research tendency. However, in bipolar disorder the mostly used indication of quetiapine is the management of acute manic phases, clinical data and the actual research results suggest that it may have both antidepressant and long-term antimanic effects. Quetiapine enhances the transmission of the central serotonergic networks, by its high antagonistic affinity for 5-HT(2A) and partial agonistic activity for the 5-HT(1A) receptors. The 5HT(1A) partial agonism causes an increase in the dopaminergic neurotransmission of the prefrontal cortex, and also, the affinity for the alpha 2-adrenoceptor brings a relative increase in extracellular noradrenergic release an tone in the prefrontal cortex. Latest research shows that quetiapine's main, active, human plasma metabolite, N-desalkyl quetiapine (norquetiapine), has a high inhibition affinity for the noradrenergic transporter. These data suggest that comparing to other atypical antipsychotics, norquetiapine may have a relatively strong antidepressant potential. Modifying the dopaminergic transmission by quetiapine's D2 receptor blocking activity results indirect mediating the cAMP-PKA and the arrestin-Akt-GSK-3 intracellular signal transduction pathways, which process may explain its long-term antimanic and mood stabilizing capability. Quetiapine's activity on nerve growth factors, histamine H1 receptor, proinflammatory networks may take an important additional part in its efficacy in bipolar depression. Its very fast dissociation from the D2 receptor is an important pharmakokinetic parameter for managing the optimal quetiapine dose in the daily clinical practice. This review tries to organize the actual information on quetiapine's multiplex activity in bipolar disorder.

1991-05-01·The Journal of pharmacology and experimental therapeutics

Clebopride enhances contractility of the guinea pig stomach by blocking peripheral D2 dopamine receptor and alpha-2 adrenoceptor.

Article

作者: Takeda, K ; Sano, I ; Ishikawa, T ; Taniyama, K ; Ohmura, I ; Kuno, T ; Tanaka, C

The mechanism of action of clebopride on the motility of guinea pig stomach was examined by the receptor binding assay for bovine brain membrane and by measuring gastric contractility and the release of acetylcholine from the stomach. The receptor binding assay revealed that clebopride bound to the D2 dopamine receptor with a high affinity and to the alpha-2 adrenoceptor and 5-HT2 serotonin receptor with relatively lower affinity, and not to D1 dopamine, alpha-1 adrenergic, muscarinic acetylcholine, H1 histamine, or opioid receptor. In strips of the stomach, clebopride at 10(-8) M to 10(-5) M enhanced the electrical transmural stimulation-evoked contraction and the release of acetylcholine. This enhancement was attributed to the blockade of the D2 dopamine receptor and alpha-2 adrenoceptor because: 1) Maximum responses obtained with specific D2 dopamine receptor antagonist, domperidone, and with specific alpha-2 adrenoceptor antagonist, yohimbine, were smaller than that with clebopride, and the sum of the effects of these two specific receptor antagonists is approximately equal to the effect of clebopride. 2) The facilitatory effect of clebopride was partially eliminated by pretreatment of the sample with domperidone or yohimbine, and the facilitatory effect of clebopride was not observed in preparations treated with the combination of domperidone and yohimbine. Clebopride also antagonized the inhibitory effects of dopamine and clonidine on the electrical transmural stimulation-evoked responses. These results indicate that clebopride acts on post ganglionic cholinergic neurons at D2 and alpha-2 receptors in this preparation to enhance enteric nervous system stimulated motility.