biostudies-literatureHarle JRoyal Society of Chemistry38053-38063https://www.ebi.ac.uk/biostudies/studies/S-EPMC10586264biostudies-literatureUnknown8(41)Recently, it was found that paracetamol can extend the therapeutic window of l-DOPA treatment for Parkinson's disease [Golding (2019) BJPharm, 4(2), Article 619]. It has been posited that the effect could be due to paracetamol and its metabolite, NAPQI, inhibiting pain signals in the spinal column. In this work, we examine the possibility that the therapeutic effect of the paracetamol for the Parkinson's disease patient may be due to an inhibition of the enzymes that metabolize dopamine and/or l-DOPA, thus effectively extending the lifetime of the l-DOPA treatment. In this work, we use the M062<i>X</i>/6-311+G* level of theory to calculate the electronic binding energies (including explicit desolvation) of several ligands (paracetamol, NAPQI, dopamine, and l-DOPA) with a series of enzymes ACS omegaInvestigating Paracetamol's Role as a Potential Treatment for Parkinson's Disease: Ab Initio Analysis of Dopamine, l-DOPA, Paracetamol, and NAPQI Interactions with Enzymes Involved in Dopamine Metabolism.PMC10586264E21-9051333819Harle JSlater CCafiero MfalseInvestigating Paracetamol's Role as a Potential Treatment for Parkinson's Disease: Ab Initio Analysis of Dopamine, l-DOPA, Paracetamol, and NAPQI Interactions with Enzymes Involved in Dopamine Metabolism.Recently, it was found that paracetamol can extend the therapeutic window of l-DOPA treatment for Parkinson's disease [Golding (2019) BJPharm, 4(2), Article 619]. It has been posited that the effect could be due to paracetamol and its metabolite, NAPQI, inhibiting pain signals in the spinal column. In this work, we examine the possibility that the therapeutic effect of the paracetamol for the Parkinson's disease patient may be due to an inhibition of the enzymes that metabolize dopamine and/or l-DOPA, thus effectively extending the lifetime of the l-DOPA treatment. In this work, we use the M062<i>X</i>/6-311+G* level of theory to calculate the electronic binding energies (including explicit desolvation) of several ligands (paracetamol, NAPQI, dopamine, and l-DOPA) with a series of enzymes 2023-01-01T00:00:00Z2023 Oct2026-06-02T18:45:22.037Z2025-05-29T19:21:39.936ZS-EPMC105862643786771810.1021/acsomega.3c03888