In Silico Screening of Compounds Similar to Codeine, Tramadol, and Morphine with Better Pharmacodynamic and Pharmacokinetics Profiles

Abstract

Introduction: Pain alleviation is the primary intervention in promoting quality of life. Among the compounds used in management of pain are opioids. Codeine is mostly used as antitussive and is commonly present in cough syrups. Tramadol and Morphine are used as analgesics based on severity of pain. Although these drugs provide instant pain relief, they are associated with many side effects and the most worrying once are addiction, respiratory depression and tolerance. Methods: Codeine, Tramadol, and Morphine were used as query compounds to generate similar compounds using SwissSimilarity. Similar compounds were docked to mu, kappa, and delta receptors and those that showed better docking scores to mu receptor and lower scores to kappa and delta were analyzed for toxicity profiles using ProTox II and pharmacokinetics profiles using SwissADME. Results: ZINC13831510; 0.992, ZINC03629718; 0. 995; ZINC03870350; 0.993; ZINC28256912; 0.992; and ZINC71774151; 0.977 showed highest binding score to mu receptors and lower to both kappa and delta. All compounds were predicted to inhibit CYP2D6 enzyme. All compounds permeated Blood Brain Barrier with the exceptions of ZINC04102208; 0.992; and ZINC13831510; 0.992. Tramadol, its zinc compounds and ZINC03629718; 0.995. were not substrates for P-glycoprotein. Tramadol and ZINC03639132; 0.976; were predicted immunoactive. All compounds conformed to Lipinski rule of five. Conclusion: In conclusion, ZINC13831510; 0.992; showed the highest binding score to morphine. ZINC02509756; 0.986; and ZINC26259212; 0.995; were considered the safest as compared to Tramadol and Codeine and their zinc compounds respectively. Further invitro studies are recommended for the following promising compounds ZINC13831510; 0.992, ZINC03629718; 0. 995; ZINC03870350; 0.993; ZINC28256912; 0.992; and ZINC71774151; 0.977 ZINC02509756; 0.986; and ZINC26259212; 0.995;.