O-Desmethyltramadol

o-desmethyltramadol (also known as o-dsmt and desmetramadol) is an opioid substance of the cyclohexanol class. it is an active metabolite of tramadol.

o-dsmt has no documented history of human use before it appeared for sale on the research chemical market in the 2010s.

subjective effects include sedation, pain relief, anxiety suppression, muscle relaxation, and euphoria. in comparison to tramadol, o-dsmt is reported to be less stimulating and feels considerably closer to a traditional opiate. being the metabolite that is mainly responsible for the analgesic effect of tramadol, o-dsmt is significantly more potent by weight than its parent compound.

o-dsmt has a very short history of human use and not much is known about its toxicity and abuse potential. it is highly advised to use harm reduction practices if using this substance.

chemistry

(+/-)o-desmethyltramadol, or 3-(2-((dimethylamino)methyl)-1-hydroxycyclohexyl)phenol, is an atypical synthetic opioid. o-desmethyltramadol is loosely analogous to codeine, but is not a morphinan opiate. instead, it contains two rings including a cyclohexane ring that is bonded to a phenyl ring at r₁. this phenyl ring is substituted at r₃ with a hydroxy group (oh-). an additional hydroxy group is found at the same location the cyclohexane ring is bonded to at the phenyl ring, r₁. o-dmst features a third substitution on its cyclohexane ring at r₂. here the ring is bonded to a dimethylamine group connected through a methylene bridge.

o-desmethyltramadol is atypical as it is found in a racemate (combination) of its stereoisomers. stereoisomers are two molecules that share the same chemical structure, but are three-dimensional mirror images of each other. tramadol is produced as a racemate of its two isomers because the combination is proven to be more effective. flipping the direction of the r₂ and r₁ bonds results in the r- and s- enantiomers of o-desmethyltramadol. o-dmst is nearly identical to tramadol, and is named for the lack of the methyl group of tramadol’s r₃ methoxy substituion.

pharmacology

o-dsmt is considerably more potent as a μ-opioid agonist compared to tramadol. additionally, unlike tramadol, it is a high-affinity ligand of the δ– and κ-opioid receptors.

the two enantiomers of o-dsmt show quite distinct pharmacological profiles; both (+) and (−)-o-dsmt are inactive as serotonin reuptake inhibitors, but (−)-o-dsmt retains activity as a norepinephrine reuptake inhibitor, and so the mix of both the parent compound and metabolites contributes significantly to the complex pharmacological profile of tramadol. while the multiple receptor targets can be beneficial in the treatment of pain (especially complex pain syndromes such as neuropathic pain), it increases the potential for drug interactions compared to other opioids, and may also contribute to side effects.

opioids exert their effects by binding to and activating the μ-opioid receptor. this occurs because opioids structurally mimic endogenous endorphins which are naturally found within the body and also work upon the μ-opioid receptor set. the way in which opioids structurally mimic these natural endorphins results in their euphoria, pain relief and anxiolytic effects. this is because endorphins are responsible for reducing pain, causing sleepiness, and feelings of pleasure. they can be released in response to pain, strenuous exercise, orgasm, or general excitement.