Opioid Notes

Opium Alkaloids

Thebaine - 6,14 Dimethoxy version of Oxymorphone. Stimulant rather than an analgesic.

Narceine - Bitter, Crystalline, formerly used as a substitute for Morphine.

Noscapine - Acts on the Sigma receptor. Non painkilling. Used commonly in Antitussives. Blocks Bradykinine B-2 receptors in Stroke patients.

Alkaloid Salt Mixtures

Pantopon - Preparation of all alkaloids present in opium without plant matter. Injectable and slightly less potent than Morphine.

Morphine Family

6-MDDM - 80x the potency of Morphine, has a faster onset and less body load then the prior.

Azidomorphine - 40x the potency of Morphine, has a high affinity for μ.

Hydromorphinol - Derivative of Morphine, yet more potent, with a steeper-dose-response curve and a longer half life. Scripted in Sweden.

Methyldesorphin - 15x the potency of Morphine. Is found in some mixtures of Krokodil.

MR-2096 - Oxymorphone analogue that is roughly the same potency.

N-Phenethylnormorphine - 8-14x the potency of Morphine.

RAM-378 - N-Phenethyl analogue of Hydromorphinol. It is probably more potent as a result.

3,6 Morphine Diesters

Diacetyldihydromorphine - Occasionally used as an alternative to diamorphine, of which it is faster acting, longer lasting and has less side effects such as euphoria and addiction. However it is equipotent with Morphine.

Dipropanoylmorphine - Ester of Morphine used to treat severe pain. Rarely used but considered to be safer and less addictive than Morphine. As such carries less side effects, such as euphoria. Slower acting, longer lasting and slightly more potent than Morphine.

Nicomorphone - 2-3x the potency of Morphine and commonly prescribed in German speaking countries.

Codeine-Dionine Family

Heterocodeine - Reverse isomer of codeine. 6x the potency of Morphine, while Codeine is a prodrug, Heterocodeine is a direct agonist.

Myrophine - Acts as a prodrug to Morphine. Has a slow onset and longer duration, but reduced potency. Does NOT produce addiction or dependence regardless of dose.

Acetyldihydrocodeine - Used in Germany. Close relative of Thebacon, where only the 6-7 cond is unsaturated. 6-Acetyl derivative of Dihydrocodeine. Metabolizes into Dihydromorphine. Higher lipophilicity than codeine. Would probably be more potent and longer lasting as a result. Higher oral BA than Codeine.

Morphinones and Morphols

14-Cinnamoyloxycodeinone - 100x the potency of Morphine.

14-Methoxymetopon - 500x the potency of Morphine. Can be up to one million times the potency of Morphine if injected into the spine.

14-Phenylpropoxymetopon - 2000x potency of Morphine. When injected into the spine up to one million times the potency of Morphine. 14-Methoxymetopon has a ceiling effect on respiratory depression, but the above has been left untested.

3-Acetyloxymorphone - Acetylated analogue of Oxymorphone.

7-Spiroindanyloxymorphone - Odd Oxymorphone analogue that is selective at dopamine.

Acetylmorphone - Acetoxy version of Hydromorphone, has a higher bioavailability as a result.

Chloroxymorphamine - Derivative of Oxymorphone and irreversible full agonist.

Methyldihydromorphone - Related to Heterocodieine not dihydrocodeine. Is 6-9x the potency of Morphine.

Metopon - Methylated Hydromorphone, less potent. More than likely would have more euphoria as a result.

N-Phenethyl-14-Ethoxymetopon - 60x the potency of Morphine, but produces less constipation. d & u agonist.

Oxymorphol - 6-Hydrogenated Oxymorphone.

Pentamorphone - Few times more potent than Fentanyl. Short duration, yet low respiratory depression.

Semorphone - 2 times the potency of Morphine. Partial u agonist and has a ceiling effect on both analgesia and respiratory depression.

Thebacon - Thebaine analogue, that is fairly uninteresting. 6-8x the potency of Codeine.

Hydrazones

Oxymorphazone - Half the potency of Oxymorphone, yet higher doses last up to 48 hours.

Morphians

Butorphanol - partial ant.-ag. at μ opioid and competitive antagonist/partial agonist at κ opioid. dysphoria is common at normal dose.

Drotebanol - Morphinan derivative synthesised from Thebaine with analgesic effects several times more potent than codeine but weaker than morphine. Moderately addictive but limited physical dependance. Under Metabanyl when available as a script.

Dextromethorphan (-) - NMDA antagonist / σ1 & σ2 sigma agonist / a3b4, a4b2, a7 nACH antagonist, (very weak) μ, δ & κ opioid agonist, SERT & NET inhibitor, NADPH Oxidase inhibitor. (Race)Methorphan = racemic

Dextrorphan (-) - NMDA antagonist / σ1 & σ2 sigma agonist / a3b4, a4b2, a7 nACH antagonist, L-Type voltage-gated calcium channel (LVGCC) blocker, SRI.

Cyclorphan - mixed antagonist-agonist with affinity for κ

Levophenacylmorphan - 10x potency of M

Levofurethylnormorphanol (Ro4-1539) - potent μ opioid agonist 30-60x potency of Levorphanol.

Levomethorphan (+) - NDMA antagonist, σ1 & σ2 sigma agonist, μ, δ & κ opioid agonist.

Levorphanol (+) - μ, κ & δ agonist, 4-8x potency of M, long duration, no cross tolerance with morphine

Norlevorphanol - Opioid analgesic, uninteresting.

Phenomorphan - 10x potency of Levorphanol. :└--> N-(2-(2-furyl)ethyl) analogue - 60x Levorphanol :└--> N-(2-(2-thienyl)ethyl) analogue - 45x Levorphanol

Proxorphan - partial κ agonist, lesser partial μ agonist

Ro4-1539 (Furethylnorlevorphanol) - 30-60x the potency of M. One of the more potent u agonists from the Morphans.

(Race)Methorphan: L(eft) (+) Levomethorphan >< Dextromethorphan (-) D(exter) --> l=OPIATE >< d=HALLUCINOGENIC OPIATE

└--> Racemic mix of both isomers, embodying their properties.

Morphinan (Racemorphan): l (+) Levorphanol >< Dextrorphan (-) d --> l=OPIATE >< :d=HALLUCINOGENIC OPIATE

└--> Racemic mix of both isomers, embodying their properties.

(Race)Allorphan: l (+) Levallorphan >< Dextrallorphan (-) d --> l= ANTI-OPIOID >< d=NMDA :ANTAGONISTS

└--> Racemic mix of both isomers, embodying their properties.

3-Hydroxymorphinan: l (+) Norlevorphanol >< Nordextrorphan (-) d --> l=OPIATE >< d=NOOTROPIC

└--> Racemic mix of both isomers, embodying their properties.

Oxilorphan: μ antagonist & weak partial κ agonist

Dimemorfan - SIGMAERGIC DRUG

Xorphanol - mixed ant.-ag. produces convulsions at highest dose tested.

Cyprodime - Selective μ opioid antagonist with no affinity for κ or δ receptors

Samidorphan - selective μ antagonist. potential for addiction treatment.

4-Phenylpiperidines

4-Fluoropethidine - In comparison to pethidine, it is 50% less potent as an analgesic but 50% more potent as a DRI. (4-iodo & 3, 4-dichloro only increase these differences)

Anileridine - Another banned pethidine analogue, probably abused. Higher analgesia than Meperidine due to n-aminophenyl group and acts withing 15 mins orally, lasting 2-3 hours.

Benzethidine - 4-phenylpiperidine analogue of pethidine. Probably somewhat more potent and euphoric. Never scripted.

Carperidine - fairly normal opiate but unused in medicine and currently LEGAL (08/06/2013)

Furethidine - 4-Phenylpiperidine analogue of pethidine. Probably a lot more potent and abuse prone. Never prescribed.

Morpheridine - related to meperidine but 4x the potency and does not cause convulsions

Phenoperidine - 20-200x the potency of Pethidine. Less hypnotic and than morphine but more emetic (nausea). This can be cured by Haloperidol.

Piminodine - similar dose to M, used in 60's and 70's but was banned. It was probably abused widely

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Prodines

Alphaprodine - 1.5x Morphine

Allylprodine - Prodine analogue 23x potency of Morphine

Betaprodine - 7.5x Morphine

Prosidol - Russian Prodine analogue

Ketobemidones

Acetoxyketobemidone - Unschedualed analogue of ketobemidone

Bemidone - Analogue of Pethidine but significantly less potent, however it has NMDA antagonism like KetoB.

Ketobemidone - μ opioid antagonist & NMDA antagonist. More addictive than M

Others

Loperamide - Peripheral opioid so it cannot cross BBB. useful anti-Diarrhoea med. When used in conjuction with Quinine or Omerprazole can cross BBB and opioid effects are seen.

Picenadol - R isomer (or Levopicenadol) is pure μ agonist while S is antagonist. Racemic is mixed that casues low abuse potential but has low κ activity

Amidones

Dipipadone - Lost Ark of the Covenant.

Phenadoxone - methadone analogue, similar dose to M, lasts 1-4 hours

Levacetylmethadol - Methadone analogue with u agonism and noncompetitive a3b4 NACh antagonism. Brand name Orlaam, prescribed to those unresponsive to methadone or subutex. Long half life (3 days) and heavier affect.

Norpipanone - Was not under international control until case reports of addiction arose.

Isomethadone - Previously used in medicine. μ- δ- agonism. S-isomer more potent.

Methadols

Dimepheptanol - Related to Methadone, has two isomers which also have two isomers so 6 possible isomers including racemic.

Moramides

Palfium (Dextomoramide) - 3x potency of M but shorter acting. High BA & fast acting, oral feels like shooting. Low LD50 & inconsistent potency (one day you may need 5mg, next day 3mg)

Thiambutens

Thiambutenes - Dimethyl-TAB, Diethyl-TAB, Ethylmethyl-TAB. Used in vetinary medicine in Japan. Banned in virtually all countried due to high abuse potential. Anticholinergic and antihistamine properties!

Phenalkoxams

Dextropropoxyphene - Low potency opiate not absorbed by CYP2D6. Also is a potent, noncompetitive α3β4 NACh antagonist and a weak SRI.

Dimenoxadol - Benzillic Acid derivative related to methadone. Banned due to high abuse potential it seems.

Dioxaphetyl butyrate - Banned opioid similar to methadone. Possibly in use or previously in use as a med under the names Amidalgon & Spasmoxal.

Ampromides

Diampromide - Banned Analgesic related to Propiram. Similar potency to M.

Propiram - Slightly more potent than codeine, 3-6hr duration. mixed μ ant.-ag. favouring agonism. affinity for κ & δ, sigma and nmda. 97% oral BA!

Others

IC-26 Methadone analogue with similar potency, but unscheduled.

Lefetamine - Weak opiate on the same scale as codeine but has DRI properties

R-4066 - Methadone analogue with 212x the potency, but a much shorter duration. (3 hours)

Amilidopiperidines

3-Methylfentanyl - 400-6000x potency of M depending on isomer (cis-iso more potent)

Alfentanil - 1/4 the potency and 1/3 the duration of fent but 4x quicker onset. The businessman's lunch of opiates.

Betahydroxythiofentanyl - one of the more favoured fent. analogues by addicts, implying euphoria.

Carfentanil - 100x potency of fent., 10000x the potency of M. Used in spetznaz hostage crisis. 10,000x potency of M. Activity in humans starts at 1μg.

Lofentanil - more potent and with a longer duration than carfentanil.

Mirfentanil - fent. analogue with strong selevtivity over μ. Lower doses it antagonises effects caused by lesser opioids but at higher doses is resistant to antagonists, suggesting it has non-opioid mechanisms.

Ohmefentanyl - 6300x morphine at it's most active isomer. Analogues of this are even stronger with one possessing 30,000x the potency of M.

Parofluorofentanyl - 150-200x morphine. Sold breifly in 1980.

R-30490 - analogue of carfentanil. Most selective μ agonist of all fentanyl analogues

Remifentanil - Potent ultra short acting fent. analogue. Potency from between 20 and 100ug. Used in medicine as an anaesthetic under Ultiva.

Sufentanil - 5-10x potency of fent

Opipavine Derivatives

7-PET - 300x potency of M, 3-OH derivative is 2200x potency of M. Unscheduled.

Acetorphine - 8700x potency of M

BU-48 - Etorphine derivative. Selective δ agonist and produces only convulsions with slight antidepression.

Buprenorphin - Subutex

Cyprenorphine - Buprenorphine analogue, ant.-ag. effects but with higher affinity towards κ.

Dihydroetorphine -1000-12000x potency of M depending on RoA. Less addictive than other opiates and is used in a similar fashion to Subutex in China.

Etorphine - 1000-3000x potency of M. μ, κ & δ opioid agonist. weak affinity for ORL1 nociceptin/orphanin FQ receptor.

Indoles

18-Methoxycoronaridine - Ibogaine derivative, selective α3β4 nicotinic antagonist, however no affinity for α4β2, NMDA or seretonin. Retains modest affinity at μ & κ opioid.

7-Hydroxymitragynine - Alkaloid in Kratom. Some 17x potency of M. 30x potency of Mitragynine

Eseroline - Metabolite of the ACh inhibitor physostigmine but potent μ agonist

Hodgkinsine - alkaloid found in Psychotria colorata plants. Has antiviral, antibacterial and antifungal properties. Also μ opioid agonist & NMDA antagonist.

Ibogaine - Addiction CURE. HT2a agonist, κ opioid agonist, NMDA antagonist

Mitragynine - Alkaloid in Kratom. Fairly selective μ agonist but little affinity for δ & κ.

Noribogaine - Metabolite of Ibogaine. Potent SRI, κ antagonist, weak μ full agonist

Voacangine - precursor to Ibogine used by iboga plant. Displays similar effects towards addiction as Ibogaine.

Diphenylmethylpiperazines

BW373U86 - Selective δ agonist at 15x stronger affinity. Analgesic and anti-depressant properties along with BDNF release. Produces convulsions at high doses and reverses respiratory depression produced by μ agonism. Also protects heart muscle cells from death during oxygen deprivation, a result of heart attacks.

DPI-227 - highly selective δ agonist with antidepressant effects but produces fewer convulsions than most other dugs in it's family.

DPI-3290 - Potent δ & μ agonist but produces little respiratory depression.

Opioid Peptides

Biphalin - endogenous eptide with high affinity for δ & μ receptors. Potency almost 7x greater than Etorphine and 7000x M. Low side effects; no dependancy caused.

Casomorphins - opiates found in Cow's milk.

DAMGO - synthetic opiate peptide with high μ selectivity. When administered alongside M for 7 days, M had the same effect at the same dose as the first day. I.e. removes tolerance.

Deltorphin - High affinity and selectivity, naturally occuring δ opioid agonist.

Dermorphin - South American Tree frog skin. Natural opioid peptide. High potency (30-40x M) and selectivity to μ but may be less likely to cause tolerance and addiction.

Dynorphins - endogenous opioid peptides, primarily k agonists. Useful in the analysis of addiction.

Leu-enkephalin - Endogeneous opioid petide that acts as a δ & μ agonist with strong selectivity for δ.

Met-enkephalin - Opioid Growth Factor (OGF), Endogenous opioid peptide. Primary ligand of the δ receptor along with Leu-enkephalin (high potency and selectivity at δ). Low BA & is metabolised rapidly.

Opiorphin - Endogenous opioid isolated from human saliva.

Others

3-HO-TCP - PCP analogue. More glutamergic than the PCP analogue.

3-HO-BCP - substitutes for both cocaine and morphine at ~5mg (made-up)

AD-1211 - Structure looks unrelated to /most/ other opioid drugs. Mixed Agonist-antagonist at opioid recepts similar to pentazocine. Little to no developement of tolerance/dependence in animal studies.

AH-7921 - Selective μ agonist, with 80% potency of M. distributed as an RC, TRs show that it has very little euphoria, indicating euphoria comes from somewhere else. Perhaps sigma? Other opioids are heavily potentiated by it. Perhaps μ agonism is purely analgesic and high comes from a combination of μ & δ with each multiplying the affect of the other. This indicates ultimate opiate high would be moderately selective δ agonist

Azaprocin - Azaprocin - ~10x potency of M. Faster onset and short duration of actin. Discoved in 1963, never been marketed. The derivative subbed on the phenyl ring with a p-nitro group would be more potent by roughly 2.5. (So 25x potency of M) The open ringed 2,6-dimethylpiperazine analouges would also be active.

BRL-52537 - Highly potent and selective κ agonist. Neuroprotective.

Bromadol (BDPC) - 500-10,000x potency of M. Similar to PCP analogues & -HO bonds within them.

C-8813 (Thiobromadol) - 591x potency of M. μ agonist & δ antagonist to reduce repiratory depression. Making the drug safer.

Ciramadol - Opioid related to PCP, Tramadol & Tapentadol. mixed ant.-ag. for μ, low abuse potential and ceiling on respiratory depression.

Enadoline - Highly selective κ agonist. Produces visual distortions, dissociation and of course dysphoria similar to Salvia.

Herkinorin - Analogue of Salvinorin A but the complete opposite. 100x higher μ affinity and 50x lower κ affinity. Also; "does not promote the recruitment of β-arrestin-2 to the intracellular domain of the μ-opioid receptor, or induce receptor internalization". This means Herkinorin may not produce tolerance or dependance.

HZ-2 - κ-opioid agonist, same potency as morphine, long duration, high oral BA

ICI-199,441 - high potency, highly selective κ agonist with analgesic effects

Methopholine - Isoquinilone derivative with same efficacy as codeine. Could produces corneal opacity. Analogues are more potent with 4'-nitromethopholine at 20x codeine.

MT-45 - 80% of M. mixed ant.-ag. and mild NMDA antagonist

Nortilidine - Equipotency of M. Opioid activity is in (1S,2R) iso, NMDA antagonism is in (1R,2S) iso. Also acts as a DRI.

O-Desmethyltramadol - metabolite of Tramadol. Considerably more potent than Tramadol. Both (+) & (-) isomers lose SRI function but (-) retains NRI functionality. RC.

Salvinorin A - Highly potent κ agonist and even more potent D2 partial agonist. Use in therapy for addiction.

Salvinorin B ethoxymethyl ether - semi-synthetic analogue of Salv. A. Longer duration @ ~3hrs, active at 50ug & 3000x (!) selectivity over μ & δ

Salvinorin B methoxymethyl ether - Similar to ^^ but less selective. 5x potency as Salvinorin A. Deacetylised from Salvinorin A.

SC-17599 - selective μ agonist with little or no affinity for δ & κ. Potency in between pethidine & morphine.

RWJ-394674 - potent and selective δ agonist, however once inside body it is dealkylated to its monodesethyl metabolite RWJ-413216 which is a potent μ agonist with less affinity for δ. δ activity counteracts the respiratory depression the μ causes. Only prominent side effect is sedation (and euphoria!)

TAN-67 - potent and selective δ1 agonist. Has analgesic properties & releases dopamine in the brain. Neuro & cardiac protective properties.

Tapentadol - μ & σ agonist & SNRI. Potency in between M & Tram.

Tifluadom - Benzo derivative but without GABAa agonism. Instead selective κ agonism.

U-47700 - Overlays betaprodine, 7.5x morphine.

U-50488 - highly selective κ agonist with analgesic effects

U-69,593 - Potent and selective κ1 agonist. Produces; antinociception, anti-inflammation, anxiolysis (low doses), respiratory depression & diuresis. Also inhibits periphery oxytocin secretion. Not sure if hallucinogenic.

W-15 - 5.4x Morphine. RC.

W-18 - 10,000x potency of M, structure abstract from any other drug. These super potent opioids are used in vetenarian practice for tranquilising elephants.

Opioid Antagonists and Inverse Agonists

(selective δ antagonists may reduce physical addiction without causing w/d if attatched to an opioid)

Chlornaltrexamine - Irreversible mixed ant.-ag. at μ opioid. 22x more potent than M

Cyprodime - Selective μ opioid antagonist with no affinity for κ or δ receptors

Diprenorphine - Strongest opiate antagonist available. 100x potency of Nalorphine. Used to reverse effects of super-potent opioids.

Levallorphan - μ opioid antagonist, when used with opiate, it potentiates it and removes addiction potential or induces withdrawal in addicts.

Nalbuphine - mixed ant.-ag. as is common with this class, there occurs analgesia with no addictive properties.

Naloxazone - Irreversible μ opioid receptor antagonist

Naloxonazine - Very Potent Irreversible μ opioid antagonist. dimerizes from Naloxazone under acidic conditions

Naltrexone - Competitive antagonist at μ & κ receptors, and to a lesser extent, δ. Modulation of the dopaminergic mesolimbic pathway makes it good for countering alcohol dependance as well as Opiate addiction. Blocks the euphoric effects of opioids and is used in rapid detoxification and attenuation of withdrawal. If opiates are used simultaneously, oD may occur.

Samidorphan - selective μ antagonist. potential for addiction treatment.

Uncategorised Opioids

FE 200665 - Is an all D-Amino acid peptide that acts as a restucted K-opioid receptor agnoist. Was dosed at 0.36mg/kg IV. Was compared to 15mg oxycodone. Slightly less than the potency of hydrocodone. Caused Hyperalgesic response in a skin pinch test. Also known as CR665.

SoRI-9409 - mixed μ agonist & δ antagonist. moderate analgesia without development of tolerance. Anti-addictive effects for all dopaminergic drugs.

Synthetic Conotoxin - Snail toxin derived painkiller 1000x potency of morphine. Non-addictive

RELATED COMPOUNDS

Amiphenazole - treatment for OD. counteracts respiratory depression. If Morphine-N-oxide is taken on this, M's potency will increase.

Chitosan - linear polysaccharide that can give Morphine up to 60% BA intranasally. Powdered & the ratio is 1.3g : 6.7g (morpine : chitosan)

BIMU-8 - NOOTROPIC

NMDA antagonists - Inhibit development of tolerance to morphine

Tezampanel - ANXIOLYTIC

Ibudilast - NOOTROPIC

Nuciferine

Tetrahydropalmatine - ANXIOLYTIC

Lofexidine - ANXIOLYTIC

d & l Phenylalanine (DLPA) - Increases dopamine and endorphin levels, reducing opiate tolerance and even providing an analgesic effect of it's own.

CCK Antagonists

Proglumide - Acts as a d opioid agonist and non selective CCK antagonist. Enhances analgesia produced by opioids and can prevent or even reverse the development of tolerance

Devazepide - No affinity for GABAa, selective CCKa antagonist.

Lorglumide - Selective CCKa antagonist for treatment of gastrointestinal problems and some forms of cancer as well as Opioid interacting properties.

Nocieceptinergic Drugs

(ORL-1 ant. & ag.'s)

J-113,397 - Highly selective ORL-1 antagonist. Prevents development of opiate tolerance, stimulates dopamine release, cognitive enhancer

SB-612,111 - Selective ORL-1 antagonist but several times the potency of ^^

MCOPPB - Potent, selective ORL-1 agonist with only moderate affinity for μ, even less for δ & κ. Anxiolytic with no inhibition of memory, motor function or sedation

NNC 63-0532 - Potent, selective ORL-1 agonist.

Ro64-6198 - Potent, selective ORL-1 agonist with 100x selectivity over others. In rats produced anxiolytic but no anticonvulsant effects. Impairs Short term memory & increases appetite. Reduces analgesic effects of M but no preventing tolerance. In primates it showed analgesic behaviour without respiratory depression.

Menabitan - potent cannabinoid receptor agonist with anti-nociceptive effects

Enkephalin Potease Inhibitors

RB-101*** - Inhibits enzymes responsible for breaking down enkephalin (regulates nociceptin). Weak μ & δ affinity and slight σ1. Potentiates opiates, stops withdrawal symptoms, no addiction potential, produces no respiratory depression. Also exerts very potent antidepressant and anxiolytic effects. Not orally active so analogues vv were developed.

RB-120 - Orally active version of the above.

RB-3007 - Another Enkeph. PI & Nociceptin antagonist