Ondansetron versus Amitriptyline in the Treatment of Peripheral Neuropathy: A Randomized Double Blind Prospective Clinical Study.

Background and Objective: Clinical trials have shown the potential use of 5-HT3 receptor antagonists like Ondansetron, Tropisetron and Zacopride in a number of disorders of gastrointestinal tract and the central nervous system such as cancer chemotherapy induced vomiting, anxiety, depression, schizophrenia and migraine. Various experimental and clinical studies also point the usefulness of Ondansetron in neuropathic pain. Therefore, the present study was conducted to find out whether Ondansetron could be used as an alternative to a standard drug, Amitriptyline in the treatment of peripheral neuropathy. Methodology: A randomized double blind prospective clinical study was conducted on Original Research Article British Journal of Medicine & Medical Research, 4(26): 4444-4454, 2014 4445 thirty six patients of peripheral neuropathy divided into two groups of equal number of patients. Group 1 received Ondansetron 8 mg per day while Group 2 received Amitriptyline 25 mg per day. Patients were being evaluated on the basis of improvements (decrease) in LANSS (Leeds Assessment of Neuropathic Symptoms and Signs), VAS (Visual Analogue Scale) and NCV (Nerve Conduction Velocity) for six weeks. Student’s ttest and/or repeated measure ANOVA followed by Bonferoni correlation was used to compare sets of paired observations. The Friedman test followed by multiple comparisons was used to compare the data which was not normally distributed. Results: LANSS and VAS scores showed significant improvements in the 1st and 2nd visit in both the groups. NCV showed improvement in Ondansetron group with less number of adverse effects compared to that of Amitriptyline. NCV in Amitriptyline group demonstrated significant increase in one of the parameters, F-waves, indicating a worsening in left tibial nerve (p=0.036), whereas no such change was found in the group treated with Ondansetron. Conclusion: Ondansetron has beneficial role in peripheral neuropathy by improving its sensory component as it significantly decreased LANSS and VAS scores. Our results also demonstrated that Ondansetron was at least as efficacious as Amitriptyline in the treatment of peripheral neuropathy with lesser adverse effects.

Anxiolytic-like effect of N-n-butyl-3-methoxyquinoxaline-2-carboxamide (6o) in experimental mouse models of anxiety.

The present research was designed to explore the anxiolytic-like activity of a novel 5-HT3 receptor antagonist (6o) in experimental mouse models of anxiety. The anxiolytic activity of '6o' at (1 and 2 mg/kg, ip) was evaluated in mice by using a battery of behavioural tests of anxiety such as elevated plus maze (EPM), light/dark aversion test, hole board (HB) and open field test (OFT) with diazepam (2 mg/kg, ip) as a standard anxiolytic. None of the tested doses of '6o' affected the base line locomotion. Compound '6o' (2 mg/kg, ip) and diazepam (2mg/kg, ip) significantly increased the percentage of both time spent and open arm entries in the EPM test. Compound '6o' in (1 mg/kg, ip) dose was only able to affect the percentage time spent in open arm significantly in the EPM test. In the light and dark test, compound '6o' (2 mg/kg, ip) and diazepam (2mg/kg, ip) significantly increased the total time spent in light compartment as well as number of transitions from one compartment to other and number of square crossed. Compound '6o' (1 and 2 mg/kg, ip) and diazepam (2 mg/kg, ip) also significantly increased number of head dips and number of squares crossed, whereas significantly decreased the head dipping latency in HB test as compared to vehicle control group. In addition, '6o' in both the doses and diazepam (2mg/kg, ip) significantly increased the ambulation scores (squares crossed) in OFT however, there was no significant effect of '6o' (1 and 2 mg/kg, ip) and diazepam (2 mg/kg, ip) on rearing scores. To conclude compound '6o' exhibited an anxiolytic-like effect in animal models of anxiety.

Anti-depressant like activity of N-n-butyl-3-methoxyquinoxaline-2-carboxamide (6o) a 5-HT3 receptor antagonist.

The compound 6o (at 0.5, 1 and 2 mg/kg, ip) with optimum log P and pA2 value, was subjected to forced swim test (FST) and tail suspension test (TST). The compound 6o significantly reduced the duration of immobility in mice without affecting the base line locomotion in actophotometer. Moreover, 6o (2 mg/kg, ip), potentiated the 5-hydroxytryptophan (5-HTP)-induced head twitch responses in mice and at 1 and 2 mg/kg, ip antagonized the reserpine-induced hypothermia (RIH) in rats. In interaction studies with various standard drugs/ligands using FST, 6o (1 and 2 mg/kg, ip) potentiated the anti-depressant effect fluoxetine (5 mg/kg, ip) and reversed the depressant effect of parthenolide (1 mg/kg, ip) by reducing the duration of immobility. Furthermore, 6o (1 and 2 mg/kg, ip) potentiated the effect of bupropion (10 mg/kg, ip) in TST. The behavioural anomalies of the olfactory bulbectomised (OBX) rats were augmented by chronic 6o (1 and 2 mg/kg) treatment as observed from the modified open field test (parameters: ambulation, rearing, fecal pellet). The results suggest that compound 6o exhibited anti-depressant like effect in rodent models of depression.

Comparison of ramosetron and ondansetron for control of post-operative nausea and vomiting following laparoscopic cholecystectomy.

Background: Post-operative nausea and vomiting (PONV) is common. 5HT 3 receptor antagonists are commonly used drugs for its prevention. A study was designed to compare the efficacy and safety of ramosetron and ondansetron in patients undergoing laparoscopic cholecystectomy (lap chole). Materials and Methods: A prospective randomized case controlled study was conducted at J. N. Medical College Hospital, Aligarh Muslim University, Aligarh, India, in patients who underwent lap chole following intravenous administration of ondansetron (4mg) or ramosetron (0.3mg) at the end of surgery, and efficacy as well as side effects of ondansetron and ramosetron was documented and compared. Results: One hundred and thirty adult females undergoing lap chole were studied - 65 patients in each of the two groups. In first 24 h after surgery, complete response (No PONV) was observed in 28 patients of the ondansetron group and in 32 patients of the ramosetron group (P>0.05). Complete response in the second 24 h after surgery was observed in 30 patients of the ondansetron group and in 45 patients of the ramosetron group (P<0.05). During the first and second 24 h, PONV requiring rescue antiemetic was significantly higher (P<0.05) in the ondansetron group as compared to the ramosetron group. Adverse drug effects in the post-operative period were observed in 11 and 8 patients in ondansetron and ramosetron groups respectively (P>0.05). Conclusion: Ramosetron was found safe and more effective antiemetic than ondansetron in patients undergoing lap chole.

Analysis of 5-HT_3 Receptor Antagonists Used in 25 Hospitals of Wuhan During the Period of 2003-2005 / 药物流行病学杂志

Objective:To evaluate the current situation and the developing trend of 5-HT3 receptor antagonists used in 25 hospital of Wuhan during the period of 2003～2005 in order to provide reference for clinical doctors and pharmacists. Method:The 5-HT3 receptor antagonists were statistically analyzed in respect to the purchase sum of money,DDDs and daily costs. Result:During the 3 years, purchase sum of money of 5-HT3 receptor antagonists were yearly increasing. The share of the market of domestic drugs showed an increasing tendency,while the imported drugs decreased year by year. Granisetron, ondansetron and tropisetron were much more frequently used than others. Conclusion:The market of the oral agents of 5-HT3 receptor antagonists will further expand in China.