title: Ondansetron: A newer aspect of dose response relationship on ileal smooth muscles of rabbit.
abstract: There are several life threatening deadly diseases in our world but ‘Cancer’ out powers them all in recent years. Chemotherapy may be used on its own or an adjunct to other forms of therapy. Despite the advancement in cytotoxic drug therapy and supportive treatment almost 70% of patient suffer from chemotherapy induced nausea and vomiting (CINV). Ondansetron, a 5-HT(3) receptor antagonist has now become a gold standard in the treatment of chemotherapy induced nausea and vomiting. The central actions of ondansetron are well established but its peripheral actions are not well recognized. The aim of our study was to explore the peripheral actions of ondansetron. Experiments were performed in five groups (n=6) and ileal smooth muscles activity was recorded on power lab (USA). The effects of increasing concentrations of acetylcholine, serotonin & ondansetron alone was observed in first three groups. In the next two groups effects of acetylcholine and serotonin pretreated with fixed concentration (1ml) of ondansetron (10¯ϖ M)were studied. The maximum response obtained by acetylcholine served as a control for our study. Maximum response with acetylcholine was taken as 100% and with serotonin was 177 percent of control. Cumulative dose response curve with ondansetron was triphasic. At 10¯ψM it was 28.8%, whereas with 10¯ξM the amplitude decreased to 16.87%, it reached to plateau at 10¯ϖ M. Response of acetylcholine & serotonin was decreased to 57% and 78% respectively in the presence of fixed concentration of ondansetron (10¯ϖ M). Ondansetron reduces the acetylcholine and serotonin induced gastrointestinal motility. Our study has indicated that ondansetron apart from having central action also has marked peripheral actions that play an important role in CINV and may act as a partial agonist.
authors.affiliation: Pharmacology Department, Wah Medical College, Wah Cantt, Pakistan.
authors.forename: Ayesha
authors.initials: A
authors.lastname: Afzal
authors.affiliation: Department of Pharmacology, Army Medical College, Abid Majeed Road, Rawalpindi, Pakistan.
authors.forename: Bushra Tayyaba
authors.initials: BT
authors.lastname: Khan
authors.affiliation: Department of Pharmacology, Army Medical College, Abid Majeed Road, Rawalpindi, Pakistan.
authors.forename: Salman
authors.initials: S
authors.lastname: Bakhtiar
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D007082:Ileum / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D017294:Ondansetron / Q000494:pharmacology*; D011817:Rabbits; D012701:Serotonin / Q000494:pharmacology
chemical_list: D012701:Serotonin; D017294:Ondansetron; D000109:Acetylcholine