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At first glance, this looks like a circular definition.

Is there some way to definitively determine if a given molecule is or is not an opioid? (Medically or scientifically, not legally).

I'm hoping for something more scientific than "if it's on this list, it is; and if it's not, it isn't."

Wikipedia's article Opioid receptor:

Opioid receptors are a group of inhibitory G protein-coupled receptors with opioids as ligands. The endogenous opioids are dynorphins, enkephalins, endorphins, endomorphins and nociceptin. The opioid receptors are ~40% identical to somatostatin receptors (SSTRs). Opioid receptors are distributed widely in the brain, and are also found in the spinal cord and digestive tract. (emphasis added)

Wikipedia's article on Opioid:

Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, treating addiction, reversing opioid overdose, suppressing cough, and suppressing opioid induced constipation. Extremely strong opioids are approved only for veterinary use such as immobilizing large mammals. Opioids are also frequently used non-medically for their euphoric effects or to prevent withdrawal. (emphasis added)

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    $\begingroup$ The common-sense answer (also given on googling) is: "Opioids are drugs that are either derived from opiates (drugs created directly from opium, such as morphine or codeine) or are chemically related to opiates or opium." $\endgroup$ Commented Aug 11, 2017 at 12:32
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    $\begingroup$ @anongoodnurse thanks, but that just pushes everything under a rug called "chemically related" which is nearly useless. It is a subjective and fluid concept; there is no litmus test for chemically relatedness. There is no common-sense here, just further ambiguity. $\endgroup$
    – uhoh
    Commented Aug 11, 2017 at 12:34
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    $\begingroup$ It's not "nearly useless" just because it breaks your question. Of course there is a definition for "chemically related". Look at PubChem or ChemIDPlus to see the structure opioids have in common. $\endgroup$ Commented Aug 11, 2017 at 12:44
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    $\begingroup$ @anongoodnurse given molecule X and Y where X is an existing synthetic opioid, and Y is a completely different synthetic opioid, is there a test, with a binary result Yes or No to the question "Is X chemically related to Y?" This needs to be a test that anyone can apply and receive the same answer in all cases. "Chemically related" is a fluid and ambiguous concept, and is not a scientifically well-defined test. $\endgroup$
    – uhoh
    Commented Aug 11, 2017 at 12:49
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    $\begingroup$ You're the one doing the dancing (semantically); I'm standing in the same position. I'm done here. $\endgroup$ Commented Aug 11, 2017 at 13:12

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First there was opium. Then the active components of opium (morphine etc.) were defined and called opiates. Then the receptors for opiates were discovered, along with their endogenous ligands (enkephalins etc.), and since those endogenous ligands were not derived from opium and indeed (being peptides) were not chemically related to opiates, a new term was needed. This term was opioid, and yes, the definition of an opioid is that it is something which binds to an opioid receptor.

The perceived circularity lies in the shift of emphasis from the drug to the receptor as the central player - when the first binding studies were being done in the early 1970s the search was for opiate receptors, not opioid receptors.

ngram

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  • $\begingroup$ The only issue I have with this answer is that endorphins, enkephalins, etc. are not listed as opioids but as "opioid peptides" (most commonly), "opioid neuropeptides", or opiate-like pentapeptides or some such, as far back as 1977. So far, I have not seen them referred to as opioids. $\endgroup$ Commented Aug 11, 2017 at 14:16
  • $\begingroup$ @anongoodnurse Ref 2 of the WP page for opioids is as follows: Hemmings et al. (2013). Pharmacology and Physiology for Anesthesia: Foundations and Clinical Application: Expert Consult - Online and Print. Elsevier Health Sciences. p. 253. ISBN 1437716792. "Opiate is the older term classically used in pharmacology to mean a drug derived from opium. Opioid, a more modern term, is used to designate all substances, both natural and synthetic, that bind to opioid receptors (including antagonists)." [my emphasis] ... $\endgroup$
    – Alan Boyd
    Commented Aug 11, 2017 at 15:05
  • $\begingroup$ ...I think the use of the term 'opioid peptide' is just a way of emphasising what is being discussed in a specific context. $\endgroup$
    – Alan Boyd
    Commented Aug 11, 2017 at 15:05
  • $\begingroup$ Perhaps, but a Google Scholar search of 2016-2017 Neuropharmacology papers on opioids fails to refer to any endogenous opioid peptides as "opioids". $\endgroup$ Commented Aug 11, 2017 at 15:24
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    $\begingroup$ The introduction to this paperInvolvement of Endogenous Enkephalins and β-Endorphin in Feeding and Diet-Induced Obesity – refers to opioid peptides as: endogenous opioids (twice); endogenous opioid peptides; endogenous ligands of opioid receptors; endogenous opioid activity; and finally states that 'This study aimed to distinguish the role of the two major classes of endogenous opioids acting at MORs and DORs, namely enkephalins and β-endorphin...'. $\endgroup$
    – Alan Boyd
    Commented Aug 11, 2017 at 18:31

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