Synthesis and Evaluation of New 1,3,4-Thiadiazole Derivatives as Antinociceptive Agents.

Mehlika Altıntop,Ümide Demir Özkay,Özgür Can,Zafer Kaplancıklı

doi:10.3390/molecules21081004

Mehlika Altıntop, Ümide Demir Özkay + Show 2 more

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https://doi.org/10.3390/molecules21081004

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Abstract

In the current work, new 1,3,4-thiadiazole derivatives were synthesized and investigated for their antinociceptive effects on nociceptive pathways of nervous system. The effects of these compounds against mechanical, thermal and chemical stimuli were evaluated by tail-clip, hot-plate and acetic acid-induced writhing tests, respectively. In addition, activity cage was performed to assess the locomotor activity of animals. The obtained data indicated that compounds 3b, 3c, 3d, 3e, 3g and 3h increased the reaction times of mice both in the hot-plate and tail-clip tests, indicating the centrally mediated antinociceptive activity of these compounds. Additionally, the number of writhing behavior was significantly decreased by the administration of compounds 3a, 3c, 3e and 3f, which pointed out the peripherally mediated antinociceptive activity induced by these four compounds. According to the activity cage tests, compounds 3a, 3c and 3f significantly decreased both horizontal and vertical locomotor activity of mice. Antinociceptive behavior of these three compounds may be non-specific and caused by possible sedative effect or motor impairments.

Highlights

Pain, an unpleasant sensation ranging in intensity from slight through severe to indescribable, is the most common symptomatic reason to seek medical consultation
1,3,4-thiadiazoles related to their antinociceptive activity [21], we reported the synthesis of a Prompted by the aforementioned findings and in continuation of our ongoing research on new series of 1,3,4-thiadiazole and focused on[21], their antinociceptive effects
1,3,4-thiadiazoles related to derivatives their antinociceptive activity we reported the synthesis of a new series of 1,3,4-thiadiazole derivatives and focused on their antinociceptive effects

Summary

Introduction

An unpleasant sensation ranging in intensity from slight through severe to indescribable, is the most common symptomatic reason to seek medical consultation. Analgesics are mainly divided into two groups: opioid analgesics and nonsteroidal anti-inflammatory drugs (NSAIDs). NSAIDs, which act primarily by inhibiting cyclooxygenase (COX) enzymes, are frequently prescribed drug groups to manage inflammatory pain. The long-term use of NSAIDs may lead to severe gastrointestinal side effects limiting their use. The adverse effects accompanying the use of nonselective NSAIDs arise from the reduction of the levels of protective prostaglandins in the gastrointestinal (GI) tract due to the inhibition of COX-1. Selective COX-2 inhibitors cause less GI adverse effects than nonselective NSAIDs, their use in the treatment is limited due to their serious cardiovascular side effects. Current research efforts are mainly directed towards the discovery of new potent analgesic drugs with fewer side effects [1,2,3,4,5,6]

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