Electrochemical Characterization of Central Action Tricyclic Drugs by Voltammetric Techniques and Density Functional Theory Calculations.

Edson Silvio Batista Rodrigues,Freddy Fernandes Guimarães,Murilo Ferreira De Carvalho,Larissa Lesley Da Silva Lima,Ricardo Menegatti,Nara Ballaminut,Vernon Somerset,Karla Carneiro De Siqueira Leite,Carlos Eduardo Peixoto Da Cunha,Bruna Guimarães Isecke,Douglas Vieira Thomaz,Fabio Bahls Machado,Eric De Souza Gil,Morgana Fernandes Alecrim,Isaac Yves Lopes De Macêdo,Mayk Teles De Oliveira

doi:10.3390/ph12030116

Edson Silvio Batista Rodrigues, Freddy Fernandes Guimarães + Show 14 more

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https://doi.org/10.3390/ph12030116

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Abstract

This work details the study of the redox behavior of the drugs cyclobenzaprine (CBP), amitriptyline (AMP) and nortriptyline (NOR) through voltammetric methods and computational chemistry. Results obtained in this study show that the amine moiety of each compound is more likely to undergo oxidation at 1a at Ep1a ≈ 0.69, 0.79, 0.93 V (vs. Ag/AgCl/KClsat) for CBP, AMP and NOR, respectively. Moreover, CBP presented a second peak, 2a at Ep2a ≈ 0.98 V (vs. Ag/AgCl/KClsat) at pH 7.0. Furthermore, the electronic structure calculation results corroborate the electrochemical assays regarding the HOMO energies of the lowest energy conformers of each molecule. The mechanism for each anodic process is proposed according to electroanalytical and computational chemistry findings, which show evidence that the methods herein employed may be a valuable alternative to study the redox behavior of structurally similar drugs.

Highlights

IntroductionCyclobenzaprine (CBP), amitriptyline (AMP) and nortriptyline (NOR) are central-acting tricyclic drugs whose applicability in therapy makes them widely prescribed medicines
Cyclobenzaprine (CBP), amitriptyline (AMP) and nortriptyline (NOR) are central-acting tricyclic drugs whose applicability in therapy makes them widely prescribed medicines. They share similar chemical structures (Figure 1), these drugs display distinct biological activities, with CBP being a muscle relaxant used against acute musculoskeletal pain while AMP and NOR are antidepressants
The voltammetric and electronic structure calculation findings corroborated the elucidation of CBP, AMP and NOR possible oxidation sites, redox reaction pathway and electrochemical profiling

Summary

Introduction

Cyclobenzaprine (CBP), amitriptyline (AMP) and nortriptyline (NOR) are central-acting tricyclic drugs whose applicability in therapy makes them widely prescribed medicines. They share similar chemical structures (Figure 1), these drugs display distinct biological activities, with CBP being a muscle relaxant used against acute musculoskeletal pain while AMP and NOR are antidepressants. Regarding CBP, the thermodynamics and kinetics of its redox processes are as yet unknown, so their elucidation is important to better understand the physicochemical features of this drug [1–3]. Pharmaceuticals 2019, 12, 116 Pharmaceuticals 2019, 12, x FOR PEER REVIEW 2 of 10 2 of 10. Sbueechn ipnefrofromrmateido,nains daptphleicmabolelectoultahreoprrbeidtailcstioenneorgf ypovsasliubele dsiiftfeesrethnacte abreetwsuesecnepetaibclhe itsoormederoxharevaectbioeenns acanldcutlhaetseedd[4a,t8a,9m].aSyubche icnofrorremlaatetidontoisealepcptrloiccahbelme tiocathl efinpdreindgicstiionnoorfdperostosibplreospiotessetphoatssairbelesuosxciedpattiibolne ptoatrhewdoaxysre[4a,c8t–io1n1s].and these data may be correlated to electrochemical findings in order to propose possiIbnlevoiexwidaotfiotnhepaitmhwpoarytsan[4c,e8–o1f1t]h. e elucidation of their redox features, this work is aimed at the cIhnarvaicetweriozfatthioenimofpCoBrtPa,nAceMoPf athnedeNluOciRdathtiroonugofhtehleeicrtrroecdhoexmfeicaatluarensd, tchoims wpuotraktiiosnaailmchedematistthrye mcheatrhaoctdesri[z8a–t1io2n]. oMf oCrBeoPv, eAr,MthPe acnodrreNlaOtiRonthberotwugehenebleoctthroacphpemroiaccahl easnwdacsodmepteurtmatiinoendalinchoermdeisrtrtyo emluetchidoadtse [a8n–d12p]r.oMpoosreeoavpeors, stihbeleceolrercetrlaotcihoenmbiectawl oeexnidabtoiothn appapthrwoaacyhoesf twheasstduedtieerdmdinruegds.in order to elucidate and propose a possible electrochemical oxidation pathway of the studied drugs

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