Opioid receptors: nootropics and compounds | sci-wiki

Naloxone

Naloxone (brand name Narcan) is an opioid antagonist used to reverse opioid overdoses; it is a rescue medication, not a drug of use. It works by blocking the mu-opioid receptor and knocking opioids off it, rapidly restoring breathing in someone who has overdosed. It has essentially no euphoric effect of its own and is a cornerstone of opioid harm reduction.

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Dissociative

3-HO-PCE

3-HO-PCE (3-hydroxyeticyclidine) is an arylcyclohexylamine of the eticyclidine (PCE) family that produces dissociative, hallucinogenic, and euphoric effects and is presumed to act as an NMDA receptor antagonist. As with other 3-hydroxy arylcyclohexylamines, the phenolic substituent is associated with added opioid-receptor activity, which may contribute sedative properties on top of dissociation. Its metabolism has been characterized in human liver microsomes and authentic urine and hair samples, proceeding through N-dealkylation, deamination, oxidation, and glucuronidation, and paralleling that of the related designer ketamine O-PCE. In silico profiling of PCE and PCP analogs suggests moderate acute toxicity with cardiotoxicity signals, while robust human pharmacological data remain scarce.

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Dissociative

3-HO-PCP

3-HO-PCP (3-hydroxyphencyclidine) is a hydroxylated analog of phencyclidine that acts as an NMDA receptor antagonist and, unusually for a dissociative, also displays notable mu-opioid receptor activity arising from its 3-hydroxy group; it is reported to be more potent than PCP itself. This dual mechanism can add opioid-like sedation and respiratory risk to the expected dissociative effects. Analytically confirmed case reports document severe toxicity, including hyperthermia, tachycardia, rhabdomyolysis, and serotonergic features, and forensic studies have quantified the drug and mapped its hepatic metabolism, noting brain concentrations exceeding those in blood. In silico work flags moderate acute toxicity and potential cardiotoxicity, while controlled human data remain absent.

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Opioid

7-Hydroxymitragynine

7-Hydroxymitragynine is a minor alkaloid of the kratom plant and an active metabolite of mitragynine, and it is the main driver of kratom's opioid-like effects. It is a potent mu-opioid receptor agonist, much stronger at that receptor than mitragynine itself, giving pain relief, sedation and euphoria. Concentrated '7-OH' products are far more potent and habit-forming than plain leaf; naloxone reverses the opioid effects.

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Opioid

Acetylfentanyl

Acetylfentanyl is a fentanyl analog and a very potent synthetic opioid, similar in structure to fentanyl but with its own risk profile. It works by strongly activating the mu-opioid receptor, producing pain relief, euphoria and heavy sedation, along with dangerous slowing of breathing. It has appeared repeatedly in the illicit drug supply and in overdose deaths; naloxone reverses its effects.

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Opioid

Desomorphine

Desomorphine is a potent semi-synthetic opioid derived from morphine, notorious in its crude homemade form 'krokodil'. It is a strong mu-opioid agonist with fast onset, short duration and heavy sedation. Its reputation for severe tissue damage comes largely from the toxic solvents and byproducts in home synthesis rather than the molecule itself, but as an opioid it carries the full overdose and dependence risk; naloxone reverses it.

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Opioid

Ethylmorphine

Ethylmorphine (Dionine) is a mild opioid closely related to codeine, an ethyl ether of morphine used historically as a cough suppressant and painkiller. It is a relatively weak mu-opioid agonist, and part of its effect comes from being metabolized toward morphine in the body. Like all opioids it carries risks of sedation, respiratory depression and dependence; naloxone reverses it.

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Opioid

Hydromorphone

Hydromorphone (brand name Dilaudid) is a strong prescription opioid used for moderate to severe pain, a semi-synthetic derivative of morphine that is several times more potent. It is a full mu-opioid agonist, producing pain relief, euphoria, sedation and respiratory depression. Like all strong opioids it carries a real overdose and dependence risk, and naloxone reverses it.

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Tryptamine

Ibogaine

Ibogaine is a naturally occurring indole alkaloid derived from the root bark of the West African rainforest shrub Tabernanthe iboga, used traditionally in Bwiti spiritual ceremonies and studied since the 1960s for a striking property: a single large dose can interrupt opioid withdrawal and reduce drug craving for extended periods. It is a genuine polypharmacological agent, engaging NMDA glutamate receptors, kappa- and mu-opioid receptors, sigma-2 sites, the serotonin transporter, and alpha3beta4 nicotinic receptors simultaneously, and it is metabolized by CYP2D6 to the long-lived active metabolite noribogaine that is thought to mediate much of its anti-addictive action. A prominent hypothesis is that ibogaine and noribogaine upregulate glial cell line-derived neurotrophic factor (GDNF) in the midbrain, resetting reward circuitry after chronic drug exposure. These effects are counterbalanced by a serious cardiac liability: ibogaine blocks the hERG potassium channel, prolongs the QT interval, and has been associated with fatal ventricular arrhythmias. It is not an approved medicine and remains investigational.

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Opioid

Oxymorphone

Oxymorphone (brand name Opana) is a strong prescription opioid for moderate to severe pain, a semi-synthetic derivative of morphine that is notably more potent. It is a full mu-opioid agonist, giving pain relief, euphoria, sedation and respiratory depression. It has a high abuse and overdose potential and, like all strong opioids, is reversible by naloxone.

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Opioid

Pethidine

Pethidine (also called meperidine, brand name Demerol) is a synthetic opioid used for moderate to severe pain, though it has fallen out of favor. It is a mu-opioid agonist giving pain relief, euphoria and sedation, but it also has serotonergic activity and a toxic metabolite, normeperidine, that can build up and cause seizures. It carries a hard rule against combining with MAOIs; naloxone reverses the opioid effects.

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Psychedelic

Salvinorin B methoxymethyl ether

Salvinorin B methoxymethyl ether (MOM-Salvinorin B) is a semi-synthetic analog of salvinorin A, the active diterpene of the plant Salvia divinorum. Like its parent it is a potent and selective kappa-opioid receptor agonist, a mechanism distinct from the 5-HT2A pathway of classic psychedelics; the receptor basis of salvinorin action has been confirmed in humans, where its subjective and physiological effects are blocked by the opioid antagonist naltrexone but not by the serotonin-2A antagonist ketanserin. In drug-discrimination studies MOM-Salvinorin B fully substitutes for salvinorin A while showing greater potency and a longer duration of action. The kappa agonism produces an intense, disorienting, and often dysphoric dissociative-psychedelic state accompanied by marked reductions in cortical blood flow, and the compound shares the atypical, difficult-to-control character of salvinorin A.

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Opioid

Sufentanil

Sufentanil is a fentanyl analog and one of the most potent opioids in clinical use, employed mainly in anesthesia and for severe pain. It is an extremely potent full mu-opioid agonist, producing profound analgesia, sedation and respiratory depression. Its sheer potency makes the margin for error tiny and overdose easy; naloxone reverses it, though repeat dosing is often needed.

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Opioid

U-47700

U-47700 is a potent synthetic opioid originally developed in research decades ago and later sold as a designer drug. It is not a fentanyl analog structurally, but it works the same way, strongly activating the mu-opioid receptor to produce pain relief, euphoria, sedation and dangerous respiratory depression. It has been implicated in many overdose deaths, and naloxone reverses its effects.

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