Opioids Enzymatic potentiation

[Allylbenzene]

P450 metabolism of morphine:

More than 90% of morphine N-demethylation could be accounted for via the action of both CYP3A4 and CYP2C8. The in vitro findings suggest that hepatic CYP3A4, and to a lesser extent CYP2C8, play an important role in the metabolism of morphine into normorphine.
— https://doi.org/10.1080/0049825031000121608

CYP3A4 inhibitors

CYP3A4 - HerbPedia

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CYP2C8 inhibitors

CYP2C8 - HerbPedia

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Glucuronidation of morphine/naloxone:

Morphine metabolism leads to the production of two predominant metabolites, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G). This metabolism involves Glucuronosyltransferase (UGT) which catalyze the addition of a glucuronide moiety onto the C3 or C6 position of morphine. Interestingly, M3G and M6G have been shown to be biologically active.
— https://doi.org/10.3389/fnmol.2022.882443

Naloxone hepatic metabolism primarily occurs via glucuronidation to form naloxone-3-glucuronide, a pharmacologically inactive metabolite.

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Some UGT enzyme inhibitors:

Glucuronosyltransferase (UGT) - HerbPedia

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Sulfation of opioid drugs:

Buprenorphine, pentazocine, and naloxone are opioid drugs used for the treatment of pain and opioid dependence or overdose. Sulfation [...] is involved in the metabolism of a variety of xenobiotics including drug compounds. Sulfation of opioid drugs has not been well investigated. Collectively, these results imply that sulfation may play a role in the metabolism of buprenorphine, pentazocine, and naloxone in vivo.
— https://doi.org/10.2174/187231212804096673

A systematic analysis using eleven known human SULTs and kinetic experiment revealed SULT1A1 as the major responsible SULTs for the sulfation of oxymorphone, nalbuphine, nalorphine, and naltrexone, SULT1A3 for the sulfation of morphine and hydromorphone, and SULT2A1 for the sulfation of butorphanol and levorphanol. Collectively, the results obtained imply that sulfation may play a significant role in the metabolism of the tested opioid drugs in vivo.
— https://doi.org/10.1016/j.ejps.2014.05.003

Sulfotransferase (SULT) are transferase enzymes that catalyze the transfer of a sulfate group from a donor molecule to an acceptor alcohol (C-OH) or amine.

Some SULT enzyme inhibitors:

Sulfotransferase (SULT) - HerbPedia

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Glutathione conjugation of opioids:

Glutathione binds not only morphine but also naloxone, methadone, and methionine enkephalin.
— https://doi.org/10.3390/ijms21176230

Glutathione S-transferase (GST) enzymes catalyze the conjugation of reduced glutathione (GSH) (using a sulfhydryl group) to electrophilic centers on a wide variety of substrates.

Some GST enzyme inhibitors:

Glutathione S-Transferase (GST) - HerbPedia

herbpedia.wikidot.com

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