a School of Bio-Science and Technology, VIT University, Vellore, Tamil Nadu, India Email: Original Article ANALGESIC, ANTI-INFLAMMATORY AND ANTIPYRETIC EVALUATIONS OF NEW ISOQUINOLINE DERIVATIVES MANIKANDAN A. a , SIVAKUMAR A.* a siva_kumar.a@vit.ac.in Received: 14 Jan 2016 Revised and Accepted: 01 Mar 2016 ABSTRACT Objective: To evaluate the isoquinoline (N-substituted (E)-4-arylidene-isoquinoline-1,3-dione) derivatives (5a-h) for their anti-inflammatory, analgesic and antipyretic activity potentials in animal models using indomethacin and diclofenac sodium as the standard. Methods: Peripheral and central analgesic activities were determined by induced writhing and tail immersion tests. Carrageenan stimulated rat paw edema model was used to evaluate the anti-inflammatory activities by examining the increase in paw volume and percentage inhibition of paw volume was calculated with plethysmometer at different time periods. Brewer’s yeast induced pyresis model was used to assessing the anti-pyretic activity by measuring the decreased rectal temperature. Results: Compounds 5g>5d>5h showed anti-inflammatory, analgesic and antipyretic activities and they were significant with p<0.001 and comparable with the control group. The results coincided with our previous report which suggests that the compounds 5g>5d>5h may take into further druggability evaluations. Conclusion: New isoquinoline derivatives produced significant anti-inflammatory, analgesic, and antipyretic activities and this suggests that these derivatives need further drug development evaluations especially for the compounds 5g>5d>5h. Keywords: N-substituted (E)-4-arylidene-isoquinoline-1,3-dione, Carrageenan, Anti-inflammatory, Analgesic, Diclofenac sodium, Antipyretic, Indomethacin © 2016 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/ ) INTRODUCTION Inflammation is a common and serious predicament in cases of hypersensitivity, autoimmune diseases, and negative response of transplanted organs [1]. Healing alternatives for inflammatory diseases generate unfavourable effects and being evidence being deficient in effectiveness. Non-steroidal anti-inflammatory drugs (NSAIDs) are precious in the healing of severe and persistent inflammation [2], fever [3], and pain [4] but long-term use of NSAIDs is related through the gastrointestinal wound, hemorrhage, and nephrotoxicity [5]. A number of isoquinoline alkaloids were reported for anti-inflammatory activity [6, 7]. We already have evaluated the in vitro anti-inflammatory [8], anticancer [9] properties of the proposed compounds. In this report, the in vivo anti-inflammatory, analgesic, and antipyretic potentials were evaluated and reported as mentioned in our previous report [8]. MATERIALS AND METHODS Chemicals λ-Carrageenan was procured from Sigma (St Louis, MO), Diclofenac Sodium was a legacy sample from Blessing Pharmaceuticals India (Maharashtra, India), Indomethacin and Brewer’s yeast from Sigma- Aldrich Chemicals, USA and all other chemicals & reagents were used analytical grade. The test compounds (E)-4-arylidene isoquinoline-1,3-diones derivatives 5(a–h) were synthesized and reported previously [8] was taken for animal studies. Chemical compounds for animal studies A mixture of homophthalic acid (1) and substituted anilines (2a-c) (1:1 ratio) in toluene and 5 mol % ZnO were amended to the suspension and refluxed. The obtained pale yellow solid compounds N-substituted homopthalimides (3a-c) were purified and characterized by FT-IR, GC-MS, 1 H NMR and [13]C NMR. Condensation of aromatic aldehydes (4a-c) with 3a-c in ethanol using oxalic acid as a catalyst to obtain the (E)-4-arylidene isoquinoline-1,3-diones derivatives 5(a–h). Animals Wistar albino rats of either sex, 50-100g, were procured from the animal house, Annamalai University, India. They were in a controlled room with a 12 h dark-light cycle and fed with commercial pellet feed from Hindustan Lever Ltd. (Mumbai, India); water was freely available. The animal model study was approved (Vide No.1038, 2013) by the Institutional Animal ethics committee of Annamalai University, India and was conducted in accordance with the “Guidelines for care and Use of Laboratory Animals", Government of India. Test of peripheral analgesic activity by acetic acid-induced writhing response The acetic acid-induced writhing test was carried out in accordance with Collier et al. [10]. The rats were intraperitoneally injected with 0.6 % acetic acid (10 ml/kg b. wt) to elicit a writhing response. Immediately after the administration of acetic acid, the animals were placed in glass cages, and the number of writhes was recorded for the following 30 min. A considerable reduction in the number of writhes by drug treatment as compared to control animals was considered as a positive analgesic response. Test compounds (50 and 100 mg/kg) and diclofenac sodium (50 mg/kg b. wt) were administered intraperitoneally 30 min before the acetic acid injection. Mean writhing and average protection values were calculated. Test of central analgesic activity of p-CA (p-Coumaric acid) by tail-immersion test The tail-immersion test was carried out as described by Janssen et al. 1963, was immersed in a water bath thermostatically maintained at 55±1 °C [11]. The time in seconds for the tail withdrawal from the water was taken as the tail withdrawal latency or reaction time, with a cut-off time of immersion set at 10 seconds. The reaction time was measured before drug treatment at 15, 30, 45 and 60 min after the drugs were administered. Test compounds (50 and 100 mg/kg) and diclofenac sodium (50 mg/kg b. wt) were administered at a lower 5- cm portion of the tail. Writhing values and average protection percentage values were calculated and tabulated. International Journal of Pharmacy and Pharmaceutical Sciences ISSN- 0975-1491 Vol 8, Issue 4, 2016