Study of the acute and repeated dose 28-day oral toxicity in mice treated with PT-31, a molecule with a potential antipsychotic profile

References

• Agostinho FR, Scaini G, Ferreira GK, Jeremias IC, Réus GZ, Rezin GT, Castro AA, Zugno AI, Quevedo J, Streck EL. 2009. Effects of olanzapine, fluoxetine and olanzapine/fluoxetine on creatine kinase activity in rat brain. Brain Res Bull. 80(6):337–340.
   PubMed Web of Science ®Google Scholar
• Aktas M, Lefebvre HP, Toutain PL, Braun JP. 1995. Disposition of creatine kinase activity in dog plasma following intravenous and intramuscular injection of skeletal muscle homogenates. J Vet Pharmacol Ther. 18(1):1–6.
   PubMed Web of Science ®Google Scholar
• Alexander J, Tibrewal P. 2010. Quetiapine-induced leucopenia. Aust N Z J Psychiatry. 44(8):767–768.
   PubMed Web of Science ®Google Scholar
• Atmaca, M, Kilic, F, Temizkan, A, Ustundag, B. 2013. What about platelet counts in clozapine users? Rev Recent Clin Trials. 8(2):74–77.
   PubMedGoogle Scholar
• Andrade RF. 2015. Antipsicóticos de segunda geração no tratamento da esquizofrenia. Rev Acad Oswaldo Cruz. 7:1–14.
   Google Scholar
• Antonelli-Ushirobira TM, Kaneshima EN, Gabriel M, Audi EA, Marques LC, Mello JCP. 2010. Acute and subchronic toxicological evaluation of the semipurified extract of seeds of guaraná (Paullinia cupana) in rodents. Food Chem Toxicol. 48(7):1817–1820.
   PubMed Web of Science ®Google Scholar
• Arivazhahan A, Bairy LK, Nayak V, Kunder SK. 2017. A study to assess the therapeutic effect of enalapril on olanzapine induced metabolic syndrome in Wistar Rats. J Clin Diagn Res. 11(2):FF01–FF06.
   PubMed Web of Science ®Google Scholar
• Aronson JK. 2009. Medication errors: definitions and classification. Br J Clin Pharmacol. 67(6):599–604.
   PubMed Web of Science ®Google Scholar
• Bessman SP, Carpenter CL. 1985. The creatine-creatine phosphate energy shuttle. Annu Rev Biochem. 54:831–862.
   PubMed Web of Science ®Google Scholar
• Betti AH, Antonio CB, Herzfeldt V, Pitta MGR, Pitta IR, Rego J-L, Rego J-C, Vaudry D, Rates SMK. 2019. PT-31, a putative α2-adrenoceptor agonist, is effective in schizophrenia cognitive symptoms in mice. Behav Pharmacol. 30(7):574–587.
   PubMed Web of Science ®Google Scholar
• Bigolin C, Oliveira TSS, Silva LC, Ayres T, Menezes JM, Pitta IR, Charão MF, Betti AH. 2020. Evaluation of the potential toxicity of haloperidol, clozapine and a new putative antipsychotic molecule, PT-31, in an alternative toxicity model, C. elegans. IJIER. 8(6):502–512.
   Google Scholar
• BRASIL 2008. Lei n° 11.794, de 8 de outubro de 2008: Regulamenta o inciso VII do § 1o do art. 225 da Constituição Federal, estabelecendo procedimentos para o uso científico de animais; revoga a Lei no 6.638, de 8 de maio de 1979; e dá outras providências. Brasília (BR): Presidência da República; [accessed 2021 Apr 30]. http://www.planalto.gov.br/ccivil_03/_ato2007-2010/2008/lei/l11794.htm.
   Google Scholar
• Brunton LL, Chabner BA, Knollmann BC. 2012. Goodman and Gilman’s the pharmacological basis of therapeutics. New York (NY): McGraw-Hill.
   Google Scholar
• Cahn W, Pol HEH, Lems EBTE, van Haren NEM, Schnack HG, van der Linden JA, Schothorst PF, van Engeland H, Kahn RS. 2002. Brain volume changes in first-episode schizophrenia: a 1-year follow-up study. Arch Gen Psychiatry. 59(11):1002–1010.
   PubMed Web of Science ®Google Scholar
• Chou AIW, Lu M-L, Shen WW. 2014. Hepatotoxicity induced by clozapine: a case report and review of literature. Neuropsychiatr Dis Treat. 10:1585–1587.
   PubMed Web of Science ®Google Scholar
• CONCEA. 2018. Resolução Normativa n° 37: Diretriz da Prática de Eutanásia do CONCEA. Brasília (BR): Conselho Nacional de Controle de Experimentação Animal; [accessed 2020 May 7] https://www.ceua.ufv.br/wp-content/uploads/2018/03/DIRETRIZ-DA-PRATICA-DE-EUTANASIA-DO-CONCEA-ATUALIZADA1.pdf.
   Google Scholar
• Cordioli AV, Gallois CB, Isolan L. 2011. Psicofármacos: Consulta Rápida, Porto Alegre (BR): Artmed.
   Google Scholar
• Correll CU, Manu P, Olshanskiy V, Napolitano B, Kane JM, Malhotra AK. 2009. Cardiometabolic Risk of second-generation antipsychotic medications during first-time use in children and adolescents. JAMA. 302(16):1765–1773.
   PubMed Web of Science ®Google Scholar
• David-Pereira A, Puga S, Gonçalves S, Amorim D, Silva C, Pertovaara A, Almeida A, Pinto-Ribeiro F. 2016. Metabotropic glutamate 5 receptor in the infralimbic cortex contributes to descending pain facilitation in healthy and arthritic animals. Neuroscience. 312:108–119.
   PubMed Web of Science ®Google Scholar
• De Meijer VE, Le HD, Meisel JA, Puder M. 2010. Repetitive orogastric gavage affects the phenotype of diet-induced obese mice. Physiol Behav. 100(4):387–393.
   PubMed Web of Science ®Google Scholar
• De With SAJ, Pulit SL, Staal WG, Kahn RS, Ophoff RA. 2017. More than 25 years of genetic studies of clozapine-induced agranulocytosis. Pharmacogenomics J. 17(4):304–311.
   PubMed Web of Science ®Google Scholar
• Del Campo A, Bustos C, Mascayano C, Acuña-Castillo C, Troncoso R, Rojo LE. 2018. Metabolic syndrome and antipsychotics: the role of mitochondrial fission/fusion imbalance. Front Endocrinol. 9:144.
   PubMed Web of Science ®Google Scholar
• Domecq JP, Prutsky G, Leppin A, Sonbol MB, Altayar O, Undavalli C, Wang Z, Elraiyah T, Brito JP, Mauck KF, et al. 2015. Clinical review: drugs commonly associated with weight change: a systematic review and meta-analysis. J Clin Endocrinol Metab. 100(2):363–370.
   PubMed Web of Science ®Google Scholar
• Doweiko JP, Nompleggi DJ. 1991. The role of albumin in human physiology and pathophysiology, Part III: albumin and disease States. J Parenter Enteral Nutr. 15(4):476–483.
   PubMed Web of Science ®Google Scholar
• Ebdrup BH, Skimminge A, Rasmussen H, Aggernaes B, Oranje B, Lublin H, Baaré W, Glenthøj B. 2011. Progressive striatal and hippocampal volume loss in initially antipsychotic-naive, first-episode schizophrenia patients treated with quetiapine: relationship to dose and symptoms. Int J Neuropsychopharmacol. 14(1):69–82.
   PubMed Web of Science ®Google Scholar
• Elkis H, Gama C, Suplicy H, Tambascia M, Bressan R, Lyra R, Cavalcante S, Minicucci W. 2008. [Brazilian Consensus on second-generation antipsychotics and metabolic disorders]. Braz J Psychiatry. 30(1):77–85.
   PubMedGoogle Scholar
• EUR-LEX. 2010. Directive 2010/63/EU of the European Parliament and of the Council of 22 September 2010 on the protection of animals used for scientific purposes. European Union (EU): European Union Law; [accessed 2021 Feb 10]. http://data.europa.eu/eli/dir/2010/63/oj.
   Google Scholar
• Flanagan RJ, Dunk L. 2008. Haematological toxicity of drugs used in psychiatry. Hum Psychopharmacol Clin Exp. 23:27–41.
   PubMed Web of Science ®Google Scholar
• Fleischhacker WW, Sanchez R, Perry PP, Jin N, Peters-Strickland T, Johnson BR, Baker RA, Eramo A, McQuade RD, Carson WH, et al. 2014. Aripiprazole once-monthly for treatment of schizophrenia: double-blind, randomised, non-inferiority study. Br J Psychiatry. 205(2):135–144.
   PubMed Web of Science ®Google Scholar
• Fraguas D, Merchán-Naranjo J, Laita P, Parellada M, Moreno D, Ruiz-Sancho A, Cifuentes A, Giráldez M, Arango C. 2008. Metabolic and hormonal side effects in children and adolescents treated with second-generation antipsychotics. J Clin Psychiatry. 69(7):1166–1175.
   PubMed Web of Science ®Google Scholar
• Galili-Mosberg R, Gil-Ad I, Weizmann A, Melamed E, Offen D. 2000. Haloperidol – induced neurotoxicity – possible implications for tardive dyskinesia. J Neural Transm. 107(4):479–490.
   PubMed Web of Science ®Google Scholar
• García-Cabezas MA, Barbas H, Zikopoulos B. 2018. Parallel development of chromatin patterns, neuron morphology, and connections: potential for disruption in autism. Front Neuroanat. 12:70.
   PubMed Web of Science ®Google Scholar
• García-Cabezas MA, John YJ, Barbas H, Zikopoulos B. 2016. Distinction of neurons, glia and endothelial cells in the cerebral cortex: an algorithm based on cytological features. Front Neuroanat. 10:107.
   PubMed Web of Science ®Google Scholar
• Gardner DM, Baldessarini RJ, Waraich P. 2005. Modern antipsychotic drugs: a critical overview. CMAJ. 172(13):1703–1711.
   PubMed Web of Science ®Google Scholar
• Gautam S, Meena PS. 2011. Drug-emergent metabolic syndrome in patients with schizophrenia receiving atypical (second-generation) antipsychotics. Indian J Psychiatry. 53(2):128–133.
   PubMedGoogle Scholar
• Girault EM, Guigas B, Alkemade A, Foppen E, Ackermans MT, Fleur SE, Fliers E, Kalsbeek A. 2014. Chronic treatment with olanzapine increases adiposity by changing fuel substrate and causes desensitization of the acute metabolic side effects. Naunyn Schmiedebergs Arch Pharmacol. 387(2):185–195.
   PubMed Web of Science ®Google Scholar
• Gora RH, Kerketta P, Baxla SL, Toppo R, Prasad R, Patra PH, Roy BK. 2014. Ameliorative Effect of Tephrosia purpurea in Arsenic-induced Nephrotoxicity in Rats. Toxicol Int. 21(1):78–83.
   PubMedGoogle Scholar
• Groover S, Hegde A, Agarwal M, Sachdeva MS. 2012. Olanzapine-associated leukopenia and thrombocytopenia managed with lithium in a patient who developed leukopenia with clozapine in the past: a case report. Int Clin Psychopharmacol 14(6):117–119.
   Google Scholar
• Hsu C-W, Lee Y, Lee C-Y, Lin P-Y. 2016. Neurotoxicity and nephrotoxicity caused by combined use of lithium and risperidone: a case report and literature review. BMC Pharmacol Toxicol. 17(1):59.
   PubMedGoogle Scholar
• Huang T-L, Lee C-T. 2007. Low serum albumin and high ferritin levels in chronic hemodialysis patients with major depression. Psychiatry Res. 152(2–3):277–280.
   PubMed Web of Science ®Google Scholar
• Hwang YJ, Dixon SN, Reiss JP, Wald R, Parikh CR, Gandhi S, Shariff SZ, Pannu N, Nash DM, Rehman F, et al. 2014. Atypical antipsychotic drugs and the risk for acute kidney injury and other adverse outcomes in older adults: a population-based cohort study. Ann Intern Med. 161(4):242–248.
   PubMed Web of Science ®Google Scholar
• Ignácio ZM, Réus GZ, Abelaira HM, Titus SE, Carlessi AS, Luz JR, Matias BI, Bruchchen L, Carvalho-Silva M, Gomes LM, et al. 2015. Acute and chronic treatments with quetiapine increase mitochondrial respiratory chain complex activity in the rat brain. Curr Neurovasc Res. 12(3):283–292.
   PubMed Web of Science ®Google Scholar
• Insel TR. 2010. Rethinking schizophrenia. Nature. 468(7321):187–193.
   PubMed Web of Science ®Google Scholar
• Ito HT, Zhang S-J, Witter MP, Moser EI, Moser M-B. 2015. A prefrontal-thalamo-hippocampal circuit for goal-directed spatial navigation. Nature. 522(7554):50–55.
   PubMed Web of Science ®Google Scholar
• Jacob R, Chowdhury AN. 2008. Metabolic comorbidity in schizophrenia. Indian J Med Sci. 62(1):23–31.
   PubMedGoogle Scholar
• Lacro JP, Dunn LB, Dolder CR, Leckband SG, Jeste DV. 2002. Prevalence of and risk factors for medication nonadherence in patients with schizophrenia: a comprehensive review of recent literature. J Clin Psychiatry. 63(10):892–909.
   PubMed Web of Science ®Google Scholar
• Laurent V, Westbrook RF. 2009. Inactivation of the infralimbic but not the prelimbic cortex impairs consolidation and retrieval of fear extinction. Learn Mem. 16(9):520–529.
   PubMed Web of Science ®Google Scholar
• Lee, J, Takeuchi, H, Fervaha, G, Powell, V, Bhaloo, A, Bies, R, Remington, G. 2015. The effect of clozapine on hematological indices: A 1-year follow-up study. J Clin Psychopharmacol. 35(5):510–516.
   PubMed Web of Science ®Google Scholar
• Legge SE, Walters JT. 2019. Genetics of clozapine-associated neutropenia: recent advances, challenges and future perspective. Pharmacogenomics. 20(4):279–290.
   PubMed Web of Science ®Google Scholar
• Minami C, Shimizu T, Mitani A. 2017. Neural activity in the prelimbic and infralimbic cortices of freely moving rats during social interaction: effect of isolation rearing. PLoS One. 12(5):e0176740.
   PubMed Web of Science ®Google Scholar
• Minns AB, Clark RF. 2012. Toxicology and overdose of atypical antipsychotics. J Emerg Med. 43(5):906–913.
   PubMed Web of Science ®Google Scholar
• Neubauer S. 2007. The failing heart-an engine out of fuel. N Engl J Med. 356(11):1140–1151.
   PubMed Web of Science ®Google Scholar
• Noh JS, Kang HJ, Kim EY, Sohn S, Chung YK, Kim SU, Gwag BJ. 2000. Haloperidol-induced neuronal apoptosis: role of p38 and c-Jun-NH(2)-terminal protein kinase. J Neurochem. 75(6):2327–2334.
   PubMed Web of Science ®Google Scholar
• OECD. 2001. Test Guideline 423: Acute Oral Toxicity – Acute Toxic Class Method. Paris (FR): Organisation for Economic Co-operation and Development; [accessed 2020 Oct 20]. https://ntp.niehs.nih.gov/iccvam/suppdocs/feddocs/oecd/oecd_gl423.pdf.
   Google Scholar
• OECD. 2008. Test Guideline 407: Repeated Dose 28-day Oral Toxicity Study in Rodents. Paris (FR): Organisation for Economic Co-operation and Development; [accessed 2020 Jun 8]. https://ntp.niehs.nih.gov/iccvam/suppdocs/feddocs/oecd/oecdtg407-2008.pdf.
   Google Scholar
• Parsons B, Allison DB, Loebel A, Williams K, Giller E, Romano S, Siu C. 2009. Weight effects associated with antipsychotics: a comprehensive database analysis. Schizophr Res. 110(1–3):103–110.
   PubMed Web of Science ®Google Scholar
• Randeva HS, Bangar V, Sailesh S, Hillhouse EW. 2000. Fatal cholestatic jaundice associated with amitriptyline. Int J Clin Pract. 54(6):405–406.
   PubMed Web of Science ®Google Scholar
• Rothschild MA, Oratz M, Schreiber SS. 1972. Albumin synthesis. N Engl J Med. 286(14):748–757.
   PubMed Web of Science ®Google Scholar
• Satoh H, Delbridge LM, Blatter LA, Bers DM. 1996. Surface: volume relationship in cardiac myocytes studied with confocal microscopy and membrane capacitance measurements: species-dependence and developmental effects. Biophys J. 70(3):1494–1504.
   PubMed Web of Science ®Google Scholar
• Shankar BR. 2007. Quetiapine-induced leucopenia and thrombocytopenia. Psychosomatics. 48(6):530–531.
   PubMed Web of Science ®Google Scholar
• Sharma V, Pandey D. 2010. Protective Role of Tinospora cordifolia against Lead-induced hepatotoxicity. Toxicol Int. 17(1):12–17.
   PubMedGoogle Scholar
• Silva JCG, Dallegrave E, Rodrigues GZP, Bigolin C, Neumann TMSO, Schuster AC, Kayser JM, Staudt LBM, Moraes MF, Farias DG. 2020. Repeated dose of meloxicam induces genotoxicity and histopathological changes in cardiac tissue of mice. Drug Chem Toxicol. 18:1–12.
   Google Scholar
• Singh KP, Singh MK, Singh M. 2016. Effects of prenatal exposure to antipsychotic risperidone on developmental neurotoxicity, apoptotic neurodegeneration and neurobehavioral sequelae in rat offspring. Int J Dev Neurosci. 52:13–23.
   PubMed Web of Science ®Google Scholar
• Singh KP, Singh MK. 2017. In utero exposure to atypical antipsychotic drug, risperidone: effects on fetal neurotoxicity in hippocampal region and cognitive impairment in rat offspring. Prog Neuropsychopharmacol Biol Psychiatry. 75:35–44.
   PubMed Web of Science ®Google Scholar
• Slim M, Medina-Caliz I, Gonzalez-Jimenez A, Cabello MR, Mayoral-Cleries F, Lucena MI, Andrade RJ. 2016. Hepatic safety of atypical antipsychotics: current evidence and future directions. Drug Saf. 39(10):925–943.
   PubMed Web of Science ®Google Scholar
• Smith KS, Graybiel AM. 2013. A dual operator view of habitual behavior reflecting cortical and striatal dynamics. Neuron. 79(2):361–374.
   PubMed Web of Science ®Google Scholar
• Stenvinkel P, Heimbürger O, Paultre F, Diczfalusy U, Wang T, Berglund L, Jogestrand T. 1999. Strong association between malnutrition, inflammation, and atherosclerosis in chronic renal failure. Kidney Int. 55(5):1899–1911.
   PubMed Web of Science ®Google Scholar
• Stępnicki P, Kondej M, Kaczor AA. 2018. Current concepts and treatments of schizophrenia. Molecules. 23(8):2087.
   PubMed Web of Science ®Google Scholar
• Sudo RT, Calasans-Maia JA, Galdino SL, Lima MCA, Zapata-Sudo G, Hernandes MZ, Pitta IR. 2010. Interaction of morphine with a new alpha2-adrenoceptor agonist in mice. J Pain. 11(1):71–78.
   PubMed Web of Science ®Google Scholar
• Sudo RT, do Amaral RV, Monteiro CEDS, Pitta IDR, Lima MDC, Montes GC, Ririe DG, Hayashida K, Zapata-Sudo G. 2017. Antinociception induced by a novel α2A adrenergic receptor agonist in rodents acute and chronic pain models. Eur J Pharmacol. 815:210–218.
   PubMed Web of Science ®Google Scholar
• Tejaswi C, Mohanan S, Murugaiyan R, Karthikeyan K. 2015. Double trouble: cyclosporine-induced thrombocytosis in a patient with methotrexate toxicity: are they related? J Pharmacol Pharmacother. 6(3):160–162.
   PubMedGoogle Scholar
• Ukai W, Ozawa H, Tateno M, Hashimoto E, Saito T. 2004. Neurotoxic potential of haloperidol in comparison with risperidone: implication of Akt-mediated signal changes by haloperidol. J Neural Transm. 111(6):667–681.
   PubMed Web of Science ®Google Scholar
• Unal B, Özbek ME, Aydın MD, Aydın N, Bulucu Z, Vuraler Ö, Odaci E, Sahin B, Kaplan S. 2004. Effect of haloperidol on the numeric density of neurons and nuclear height in the rat hippocampus: a stereological and histopathological study. Neurosci Res Comm. 34(1):1–9.
   Google Scholar
• Van De Werd HJJM, Uylings HBM. 2014. Comparison of (stereotactic) parcellations in mouse prefrontal cortex. Brain Struct Funct. 219(2):433–459.
   PubMed Web of Science ®Google Scholar
• Varghese D, Kirkwood CK, Carroll NV. 2016. Prevalence of antidiabetic and antilipidemic medications in children and adolescents treated with atypical antipsychotics in a Virginia Medicaid Population. Ann Pharmacother. 50(6):463–470.
   PubMed Web of Science ®Google Scholar
• Verrico MM, Nace DA, Towers AL. 2000. Fulminant chemical hepatitis possibly associated with donepezil and sertraline therapy. J Am Geriatr Soc. 48(12):1659–1663.
   PubMed Web of Science ®Google Scholar
• Vo, QT, Thompson, DF. 2019. A review and assessment of drug-induced thrombocytosis. Ann Pharmacother. 53(5):523–536.
   PubMed Web of Science ®Google Scholar
• Wasti A, Ghani R, Manji MA, Ahmed N. 2017. Clozapine induced neutrophil cytotoxicity in rats. J Pak Med Assoc. 56(2):62–65.
   Google Scholar
• WHO. 2019. Schizophrenia. Geneva (CH): World Health Organization; [accessed 2020 Mar 26]. http://www.who.int/mediacentre/factsheets/fs397/en/.
   Google Scholar
• Zugno AI, Barcelos M, Oliveira L d, Canever L, Luca RDd, Fraga DB, Matos MP, Rezin GT, Scaini G, Búrigo M, et al. 2012. Energy metabolism, leptin, and biochemical parameters are altered in rats subjected to the chronic administration of olanzapine. Braz J Psychiatry. 34(2):168–175.
   PubMedGoogle Scholar