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 Morphine, has a faster onset and less body load then the prior.

Azidomorphine - 40x 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 Morphine. Is found in some mixtures of Krokodil.

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

N-Phenethylnormorphine - 8-14x 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 Morphine and commonly prescribed in German speaking countries.

Codeine-Dionine Family

Heterocodeine - Reverse isomer of codeine. 6x 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 bond 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 Morphine.

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

14-Phenylpropoxymetopon - 2000x potency of Morphine. When injected into the spine up to one million times 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 Morphine.

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

N-Phenethyl - 14-Ethoxymetopon - 60x 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 - 2x Morphine. Partial u agonist and has a ceiling effect on both analgesia and respiratory depression.

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

Hydrazones

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

Morphians

Butorphanol - Partial agonist-antagonist 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 Morphine.

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 Morphine. One of the more potent u agonists from the Morphans.

(Race)Methorphan: L(eft) (+) Levomethorphan >< Dextromethorphan (-) D(exter) :--> l = Opioid >< d = Hallucinogenic opioid.

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

Morphinan (Racemorphan): l (+) Levorphanol >< Dextrorphan (-) d --> l = Opioid >< :d = Hallucinogenic opioid.

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

(Race)Allorphan: l (+) Levallorphan >< Dextrallorphan (-) d --> l = Opioid antagonist >< d = NMDA antagonist.

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

3-Hydroxymorphinan: l (+) Norlevorphanol >< Nordextrorphan (-) d --> l = :Opioid >< d = Nootropic.

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

Oxilorphan: μ antagonist & weak partial κ agonist.

Dimemorfan - Sigmaergic drug.

Xorphanol - Mixed agonist-antagonist 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.

Benzomorphans

Butinazocine - Benzomorphan opioid that was never marketed.

Carbazocine - Benzomorphan opioid that was never marketed.

Etazocine - Partial opioid agonist with mixed agonist-antagonist effects. Low potency.

Ethylketocyclozocine - Partial opioid agonist with mixed agonist-antagonist effects.

Ibazocine - Benzomorphan opioid that was never marketed.

Moxazocine - 10x potency of Morphine, partial/mixed agonist-antagonist.

Tonazocine - Partial agonist at μ & δ, no adverse effects on breathing.

Volazocine - Benzomorphan opioid that was never marketed.

Fluorophen - Radioligand, full μ agonist (6x Morphine) & lower affinity for δ.

Zenazocine - Partial agonist at μ & δ.

Eptazocine - Japanese κ agonist & μ antagonist.

Pentazocine - Mixed agonist-antagonist (-) is the κ agonist side, the (+) displays 10x the affinity for sigma receptors. NO μ agonism.

Phenazocine - Related to ^ but stronger analgesic, 4x potency of Morphine.

Cyclazocine - Mixed agonist-antagonist.

Dezocine - Mixed agonist-antagonist with high κ antagonism. Low dose=euphoria (μ), high dose=dysphoria (κ). Weird structure.

8-Carboxamidocyclazocine (8-CAC) - κ & μ agonist, long duration.

Bremazocine - κ agonist related to Pentazocine.

Metazocine - Analgesic; mixed agonist-antagonist at μ, activity also at κ and sigma.

Alazocine - σ1 agonist, κ opioid agonist & slight NMDA antagonist.

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 opioid but unused in medicine.

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 Pethidine. Less hypnotic and than morphine but more emetic (nausea). This can be cured by Haloperidol.

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

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 Ketobemidone.

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

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 antagonisMorphine. 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- agonisMorphine. 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 (Dextromoramide) - 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 opioid 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 PropiraMorphine. Similar potency to Morphine.

Propiram - Slightly more potent than codeine, 3-6hr duration. mixed μ agonist-antagonist favouring agonisMorphine. affinity for κ & δ, sigma and NMDA. 97% oral BA!

Others

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

Lefetamine - Weak opioid 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 Morphine depending on isomer (cis-iso more potent).

4-Fluorobutyrfentanyl - Short duration.

Acetylfentanyl - 80x Morphine.

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

Betahydroxythiofentanyl - One of the more favoured fentanyl analogues by addicts, implying euphoria.

Butyrfentanyl - 20-25x Morphine.

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

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

Mirfentanil - Fentanyl 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 Morphine.

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 - 150-200x the potency of Morphine.

Opipavine Derivatives

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

Acetorphine - 8700x potency of Morphine.

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

Buprenorphin - Subutex.

Cyprenorphine - Buprenorphine analogue, agonist-antagonist effects but with higher affinity towards κ.

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

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

Pirinitramides

Bezitramide - Prodrug that hydrolyzises in the GI tract to despropionyl-bezitramide. Pulled from the NL's in 2004 after fatal overdose cases.

Piritramide - 0.65-0.75x M but still effect is strong and long lasting. Has a small but dedicated fanclub on the 'street'

Benzimidazoles

Etonitazene - Most potent nitazene at 1000-1500x potency of M. Strange structure, abstract from other opioids, with an indole body.

xxxNitazene - Differing potencies depending on substitution on the lower 4-phenyl.

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 KratoMorphine. Some 17x potency of Morphine. 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 - 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.

Pyrroles

Viminol - Mixed agonist-antagonist, 5.5x Morphine.

Pyrollidone-Viminol - 318x Morphine.

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 agonist Morphine. 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 Morphine. Low side effects; no dependancy caused.

Casomorphins - Opioids found in Cow's milk.

DAMGO - Synthetic opioid 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.

Azaprocin - Azaprocin - ~10x potency of Morphine. 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 Morphine. Similar to PCP analogues & -HO bonds within them.

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

Ciramadol - Opioid related to PCP, Tramadol & Tapentadol. mixed agonist-antagonist 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 Morphine. mixed agonist-antagonist and mild NMDA antagonist.

Nortilidine - Equipotency of Morphine. 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. Used in therapy for addiction.

Salvinorin B ethoxymethyl ether - Semi-synthetic analogue of Salvinorin 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 Morphine & Tramadol.

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

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-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 agonist-antagonist at μ opioid. 22x more potent than Morphine.

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

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

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

Nalbuphine - Mixed agonist-antagonist 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 opioid addiction. Blocks the euphoric effects of opioids and is used in rapid detoxification and attenuation of withdrawal. If opioids 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 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 (morphine : 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 opioid tolerance and even providing an analgesic effect of it's own.

CCK Antagonists

Proglumide - Acts as a δ-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 opioid tolerance, stimulates dopamine release, cognitive enhancer

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

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 Morphine but does not prevent 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 opioids, 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.