Effect of Fluoxetine and Paroxetine on Intestinal Motility in Presence of Ondansetron in ex-vivo Model
SSRIs and Ondansetron
Abstract
Objective: To understand the effects of fluoxetine and paroxetine with ondansetron on the intestinal motility of rabbit ileum.
Study Design: Observational study.
Place and Duration of Study: The study was conducted from March to April 2018 in a multidisciplinary lab of Army Medical College, Rawalpindi.
Materials and Methods: The contractile effect of intestinal motility was recorded in the power lab. Subjects were twenty four healthy rabbits (Oryctolagus Cuniculus). Semi log dose-response curve was constructed for increasing concentrations of serotonin, ondansetron, fluoxetine, and paroxetine (10-9 to 10-6 M) alone and then in the presence of a fixed concentration of ondansetron (10-6 M) to observe the modulatory role of ondansetron. The serotonin mediated contractions were taken as control.
Results: Ondansetron and serotonin caused an increase in the contractile response of rabbits ileum. A depressive response was observed when the contractions were recorded with increased concentration of fluoxetine and paroxetine in the presence of ondansetron.
Conclusion: Ondansetron when used concomitantly with selective serotonin reuptake inhibitors(SSRIs), abolishes their antidepressant effects by causing a decrease in the intestinal motility of rabbit ileum.
References
Cecille B, Adeline E, Chris O, Bjarka E, Connie S, Nasser H. Role of 5-HT3 receptors in the Antidepressant Response. Pharmaceuticals. 2011; 4: 603-29.
Richards R. Is chemotherapy always necessary for breast cancers? Ehow Health (newsletter) National Cancer Institute, National Institutes of Health. 2013.
Afzal A, Khan BT, Bakhtiar S. Ondansetron: A newer aspect of the dose-response relationship on ileal smooth muscles of rabbit Pak. J. Pharm. Sci. 2016; pp: 119-24.
Afzal A, Ajmal K, Sabeen S. Paroxetine: An update of response on intestinal motility J Pak Med Assoc. 2016; 66: 240-2.
Cohen IT. An overview of the clinical use of ondansetron in preschool-age children. Ther Clin Risk Manag. 2007; 3: 333- 9.
Devita VT, Rosenberg SA. Two Hundred Years of Cancer Research. N. Engl. J. Med. 2012; 366: 2207-14.
Rogers MP, Blackburn L. Use of neurokinin-1 receptor antagonists in patients receiving moderately or highly emetogenic chemotherapy. Clinical. J. ONS. 2010; 14: 500–4.
Spiller R. Serotonergic modulating drugs for functional gastrointestinal diseases. Br. J. Pharmacol. 2002; 54: 11-20.
Jabeen Q, Aziz N, Afzal Z, Gilani HA. The spasmogenic and spasmolytic activities of Lavandula Stoechas are mediated through muscarinic receptor stimulation and calcium channel blockade. Int. J. Pharmacol. 2007; 3: 61-7.
Noor A, Najmi MH, Bakhtiar S. Effect of bradykinin-induced contraction on isolated smooth muscle of guniea pig . Indian Journal of Pharmacology. 2011; 43: 449-55.
Bajetta E, Puscedd S, Guadalupi V, Ducceschi M, Celio L. Prevention of acute chemotherapy-induced nausea and vomiting. The role of palonosetron. Cancer Manag Reo. 2009; 1: 89-97.
Barrack S. Selective serotonin reuptake inhibitors (SSRIs). J.NeurologyVersion. 2016; 29: 954-6.
Basch E, Abernethy AB. Supporting clinical practice decisions with the real-time-patient-reported outcome. J
Clin Oncol. 2011; 29: 954-6.
Chetty N, Irving RH, Coupar MI. Activation of 5-HT3 receptors in the rat and mouse intestinal tract: A
comparative study. Br. J. Pharmacol. 2006; 148: 1012-21.
Gregory VC, Lucki I. The role of serotonin receptor subtypes in treating depression: A review of animal studies.
Psychology. 2010; 213: 265-87.
Hajdu SI, Thun MJ, Hannan LM, Jemal A. A note from history: Landmark in history of cancer. Cancer 2011; 117:
-102.
Hawkin's R, Gunberg S. Chemotherapy-induced nausea and vomiting. Challenges and opportunities for improved patient outcomes. Clin. J. Oncol. Nurs. 2009; 13: 54-64.
Janssen P, Oudenhove VL, Castcels C, Vos R, Verbeke K, Tack J. The effect of acute citalopram dosing on gastric motorfunction and nutrient tolerance in healthy volunteers. Aliment Ther. 2010; 33: 395-402.
Mujezinovic I, Cupic V, Samajlovic A, Muminovic M. Identification of serotonergic (5-H1A-Type) receptor in broiler small intestine by application of its serotonin and antagonist. Vetnary glasnick. 2011; 65: 51-9.
Mir O, Durand JP, Boudou-Rouquette P, Giroux J, Coriat R, Cessot A, et al. Interaction between serotonin reuptake inhibitors, 5-HT3 antagonists, and NK1 antagonists in cancer patients receiving highly emetogenic chemotherapy: a case-control study. 2012; 20: 2235-9.
Mujezinovic I, Cupic V, Samajlovic A, Muminovic M. Identification of serotonergic (5-H1A-Type) receptor in broiler small intestine by application of its serotonin and antagonist. Vet. glasnick. 2011; 65: 51-9.
Pithadia BA, Jain MS. 5-Hydroxytryptamine receptor subtypes and their modulation with therapeutic Potentials. J. of Clin. Med Res. 2009; 1: 72-80.