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Biochemical Methods of Studying Hepatotoxicity
Published in Robert G. Meeks, Steadman D. Harrison, Richard J. Bull, Hepatotoxicology, 2020
Prasada Rao S. Kodavanti, Harihara M. Mehendale
In the liver, ALP is associated with both sinusoidal and canalicular membranes (Hagerstrand, 1975) and its elevations in serum are indicative of cholestasis. Industrial chemicals are not usually associated with this type of response, although a large number of drugs (including amitriptyline, chlorpromazine, chlorthiazide, diazepam, fluphenazine, imipramine, methimazole, nitrofurantoin, penicillamine, promazine, thiouracil, and triflupromazine) do cause intrahepatic cholestasis (Popper and Schaffner, 1959; Schaffner and Raisfeld, 1969; Zimmerman, 1978).
Halogen Labeled Compounds (F, Br, At, Cl) *
Published in Garimella V. S. Rayudu, Lelio G. Colombetti, Radiotracers for Medical Applications, 2019
CF3 is an important moiety in medicinal chemistry. Its presence in a molecule often results in enhancement of biological activity, e.g., triflupromazine and trifluperidol. Palmer et al.50 suggested the possibility of labeling CF3 with 18F in place of Br, CH3, or NO2. Ido et al.51 were able to incorporate 18F into CF3 moiety of several organic compounds by exchange reactions with K18F in the presence of a crown ether.
Supercritical Fluid Chromatography
Published in Steven H. Y. Wong, Iraving Sunshine, Handbook of Analytical Therapeutic Drug Monitoring and Toxicology, 2017
Berger and Wilson56,57 systematically investigated the SFC retention and selectivity of antidepressants and phenothiazine antipsychotics by using a packed cyanopropyl column at various ternperatures. The tertiary mobile phase consisted of carbon dioxide, methanol, and isopropylamine. For a mixture of ten antidepressants—amitriptyline, imipramine, nortriptyline, desipramine, pro-triptyline, buclizine, benactyzine, hydroxyzine, perphenazine, and thioridazine—analysis for five selected antidepressants was completed in less than 6 min (as shown by Figure 4–11), with a detection limit of 88 ppb (ng/ml), and for ten phenothiazines—triflupromazine, carphenazine, methotrimeprazine, promazine, molindone, perphenazine, chloroprothixine, deserpidine, thiothixene, and reserpine—11 min at 88 ppb (ng/ml) (as shown by Figure 4–12). Changing modifier concentration significantly affected the selectivity for antidepressants, but not for phenothiazines. Temperature programming offered the best resolution of phenothiazines.
Antihistamines, phenothiazine-based antipsychotics, and tricyclic antidepressants potently activate pharmacologically relevant human carbonic anhydrase isoforms II and VII
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2023
Francesco Fiorentino, Alessio Nocentini, Dante Rotili, Claudiu T. Supuran, Antonello Mai
The cytosolic hCA II was activated by all tested compounds, apart from 2. Specifically, all compounds exhibited improved KA values over 1 for this isoform. Phenothiazines 6–10, and TCAs 13 and 14 displayed KA values lower than 5 µM, with norpromazine (8) being the most potent hCA II activator (KA = 1.4 µM), immediately followed by triflupromazine (10) and imipramine (13), with KA values of 1.9 and 2.0 µM, respectively. Notably, demethylation had divergent effects on hCA II activation for 13 and the rest of the assayed compounds. Indeed, the double demethylation of 5 and the mono demethylation of 7, leading to 6 and 8, respectively, increased the hCA II activation profile by 1.5- to 2.6-fold. Similarly, removal of a methyl group from 15 augmented hCA II activation [KA(15) = 18.9 µM, KA(16) = 11.7 µM], while the opposite effect was observed in the case of 13, since its mono desmethyl derivative 14 was ∼2-fold less potent.
Multi-targeted drug design strategies for the treatment of schizophrenia
Published in Expert Opinion on Drug Discovery, 2021
Piotr Stępnicki, Magda Kondej, Oliwia Koszła, Justyna Żuk, Agnieszka A. Kaczor
The wide group of first generation antipsychotics may be divided into several classes according to the chemical structures of its representatives. The most important groups are phenothiazines (e.g. chlorpromazine, promazine, triflupromazine), butyrophenones (e. g. haloperidol, droperidol, benperidol) and thioxanthenes (e.g. clopenthixol, flupenthixol) [31]. These drugs affect wide spectrum of receptors, leading to numerous adverse effects. The most frequent, resulting from blocking nigrostriatal dopamine D2 receptors, are extrapyramidal effects (e.g. unwanted movements, dyskinesia, akathisia, dystonias). Antagonism to this receptor in tuberoinfundibular circuit leads in turn to excessive prolactin release. Antihistaminic profile of first generation antipsychotics causes sedation, whereas blocking α1 adrenergic receptors may result in hypotension [32].
The broad-spectrum antiviral recommendations for drug discovery against COVID-19
Published in Drug Metabolism Reviews, 2020
Abu Hazafa, Khalil ur-Rahman, Ikram-ul- Haq, Nazish Jahan, Muhammad Mumtaz, Muhammad Farman, Huma Naeem, Faheem Abbas, Muhammad Naeem, Sania Sadiqa, Saira Bano
Frieman et al. (2019) reported that a significant concentration of diverse neurotransmitter inhibitors results in the formation of useful antiviral to reduce or control the coronavirus activity by at least 50% (IC50). They reported that early administration of neurotransmitter inhibitors, including triflupromazine hydrochloride, and chlorpromazine hydrochloride in a range of 5.76–12.9 µM are proved as good therapeutic targets to control the coronavirus (MERS-CoV and SARS-CoV) by inhibiting the dopamine receptor. Similarly, the kinase signaling inhibitors including dasatinib and imatinib mesylate within the administration dose of about 2.1–17.6 µM significantly showed the antiviral activity against MERS and SARS coronaviruses by at least 50% (IC50) via blocking the endosomal fusion or inhibiting the viral RNA formation. Moreover, the estrogen receptor inhibitors including tamoxifen citrate and toremifene citrate and DNA metabolism inhibitor namely gemcitabine hydrochloride (1.2–4.9 µM) reduced the coronavirus by inhibiting the viral DNA replication and repair (Johansen et al. 2013; Madrid et al. 2013; Frieman et al. 2019). The in vitro study of different inhibitors against coronaviruses are presented in Table 1. These different inhibitors could be used in combination with several drugs, including brivudine, penciclovir, cidofovir, zanamivir, and ribavirin, interferons to develop a novel therapeutic agent to control the newly induced coronavirus (Frieman et al. 2019).