title: Gastroprotective potential of risperidone, an atypical antipsychotic, against stress and pyloric ligation induced gastric lesions.
abstract: Risperidone has been used in some stress disorders and may be potentially protective against stress-induced gastric lesions. Thus, the aim of the present study is to investigate, whether risperidone, a D(2) receptor and 5-HT(2A) receptor antagonist, would be able to result in gastroprotective effect in stress-induced lesions and also explore the possible mechanism of action behind its gastroprotective activity. Gastroprotective activity of risperidone was evaluated both by single treatment and 21 days repeated (0.03, 0.1, 0.3 and 1mg/kg, p.o.) treatment in the cold restraint stress (CRS) model and 21 days repeated treatment in the pyloric ligation (PL) model and compared with that of sulpiride (D(2) receptor antagonist) and ketanserin (5-HT(2) receptor antagonist) as standard. Histopathological assessment was done to evaluate the gastroprotective activity of risperidone in CRS model. The roles of nitric oxide (NO), sulfhydryl (SH) group, ATP-sensitive K(+) channels (K(ATP) channels) and prostaglandins (PGs) in the gastroprotective effect of risperidone against CRS were also investigated. PGE(2), hexosamine as a marker of mucus barrier and microvascular permeability were also estimated. Results show that repeated treatment of risperidone, sulpiride and ketanserin exhibited a gastroprotective effect against CRS-induced lesions while single administration of risperidone was found to be ineffective. Moreover, repeated treatment of risperidone and ketanserin was found to be ineffective in case of PL in contrast to sulpiride. Risperidone pretreatment reverses the stress induced alteration in hexosamine, PGE(2) and microvascular permeability. Pretreatment with l-NAME, NEM, glibenclamide and indomethacin reversed the gastroprotective effect of risperidone. The results suggest that risperidone has significant gastroprotective effects in CRS-induced gastric lesions models, which appears to be mediated by endogenous NO, SH, PGs and K(ATP) channel opening.
authors.affiliation: Department of Pharmaceutics, Institute of Technology, Banaras Hindu University, Varanasi, Uttar Pradesh 221005, India.
authors.forename: Bhagawati
authors.initials: B
authors.lastname: Saxena
authors.forename: Sairam
authors.initials: S
authors.lastname: Krishnamurthy
authors.forename: Sanjay
authors.initials: S
authors.lastname: Singh
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects; D015232:Dinoprostone / Q000378:metabolism / Q000502:physiology; D004195:Disease Models, Animal; D065127:Dopamine D2 Receptor Antagonists; D005905:Glyburide / Q000633:toxicity; D006595:Hexosamines / Q000378:metabolism; D007213:Indomethacin / Q000633:toxicity; D054086:KATP Channels / Q000378:metabolism / Q000502:physiology; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000633:toxicity; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D044348:Receptors, Serotonin, 5-HT2 / Q000737:chemistry / Q000378:metabolism; D018967:Risperidone / Q000494:pharmacology*; D013276:Stomach Ulcer / Q000473:pathology / Q000517:prevention & control*; D013312:Stress, Physiological; D013438:Sulfhydryl Compounds / Q000378:metabolism / Q000502:physiology; D013469:Sulpiride / Q000494:pharmacology
chemical_list: D014150:Antipsychotic Agents; D065127:Dopamine D2 Receptor Antagonists; D006595:Hexosamines; D054086:KATP Channels; D017448:Receptors, Dopamine D2; D044348:Receptors, Serotonin, 5-HT2; D013438:Sulfhydryl Compounds; D009569:Nitric Oxide; D013469:Sulpiride; D007650:Ketanserin; D015232:Dinoprostone; D018967:Risperidone; D005905:Glyburide; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin