eJManager REVIEW ARTICLE Open Access Preclinical screening techniques for ant-diarrheal drugs: a comprehensive review Erhirhie Earnest Oghenesuvwe 1 , Emudainohwo Joseph Oghenebrorie Tedwins 2 , Igboeme Sabaste Obiora 1 , Ajaghaku Daniel Lotanna 3 , Ujam Nonye Treasure 4 , Okezie Moses Ugochukwu 5 , Ilodigwe Emeka Emmanuel 1 1 Department of Pharmacology and Toxicology, Faculty of Pharmaceutcal Sciences, Nnamdi Azikiwe University, Awka, Nigeria 2 Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Benin, Benin City, Nigeria 3 Department of Pharmacology, Faculty of Pharmaceutcal Sciences, Enugu State University of Science and Technology, Agbani, Enugu State, Nigeria 4 Department of Pharmaceutcs and Pharmaceutcal Technology, Faculty of Pharmaceutcal Sciences, Enugu State University of Science and Technology, Agbani, Enugu State, Nigeria 5 Department of Pharmaceutcal Biology and Biotechnology, Faculty of Pharmaceutcal Sciences, Nnamdi Azikiwe University, Awka, Nigeria ABSTRACT Diarrhea is a global epidemic mostly common in developing countries, especially among children below 5 years. The side efects posed by conventonal ant-diarrheal agents necessitate the screening and development of alternatve agents. This review assessed the current experimental techniques involved in screening agents with promising ant-di- arrheal propertes. The various models described include in vivo model (gastrointestnal transit tme using charcoal meal, castor oil-induced diarrhea, castor oil-induced entero- pooling, magnesium sulfate-induced diarrhea, prostaglandin (PGE 2 )-induced entero- pooling, and serotonin-induced diarrhea), intestnal enteroids model (enterotoxigenic escherichia coli-induced diarrhea, enteropathogenic escherichia coli-induced diarrhea, and cholera toxin-induced diarrhea) as well as ex vivo model (involving the use of iso- lated jejunum or ileum from guinea pigs, rabbits, and rats). Innovatve screening areas covered include enkephalinase, intestnal ion channels, infammatory bowel disease associated diarrhea and farnesoid X receptor target. Advantages and disadvantages of these techniques were also highlighted. Applicaton of these models would aid research- ers in the discovery of alternatve ant-diarrheal agents. ARTICLE HISTORY Received 29 March 2018 Accepted 14 June 2018 Published 23 June 2018 KEYWORDS Experimental screening models; in vivo diarrhea models; ex vivo diarrhea model; in vitro diarrhea model; enteroids diarrhea model Introducton Diarrhea, a word derived from Greek (dia, through) and Latin (rheein, to flow or run), involves the pas- sage of loose or watery stools that occurs at least three times daily [1]. It is characterized by an increased frequency of bowel (more than two stool above 200 g per day), watery stools, presence of blood in stools, steatorrhea, nausea, loss of appetite and weight, vomiting, and abdominal pains [2]. According to the World Health Organization, diarrhea had been reported to be the major cause of morbidity and mortality in several develop- ing nations where about three to five billion cases of diarrhea occur each year with children below 5 years of age accounting for about one billion of these cases [3,4]. Diarrhea may be due to exposure of an individ- ual to contaminated or wrong diet, which could lead to infection as well as disruption in the intes- tinal absorptive and secretory functions [4]. Other causes include bacterial infections, salmonella, Vibrio cholera, Shigella, enterotoxigenic Escherichia coli, Campylobacter spp., enteric parasites (such as Cryptosporidium spp., Giardia lamblia, Entamoeba histolytica, and Blastocystis hominis), virus, psycho- logical stress, anxiety, and side effects originating from some medications [5–7]. Diarrhea could be acute, caused by parasitic infections that may last for 1–2 days or chronic, Contact Earnest Oghenesuvwe Erhirhie erhirhieochuko@yahoo.com Department of Pharmacology and Toxicology, Nnamdi Azikiwe University, Agulu, Nigeria. © EJManager. This is an open access artcle licensed under the terms of the Creatve Commons Atributon Non-Commercial License (htp:// creatvecommons.org/licenses/by-nc/3.0/) which permits unrestricted, noncommercial use, distributon and reproducton in any medium, provided the work is properly cited. AMERICAN JOURNAL OF PHYSIOLOGY, BIOCHEMISTRY AND PHARMACOLOGY , 2018 VOL 7, NO. 2, PAGE 61–74 10.5455/ajpbp.20180329014330